Let’s face it; it’s like America is missing it by paying more attention to Gun Violence murder and other deadliest diseases than opioid addiction that leads to an average number of deaths of 130 people every day. There is no doubt; the United States is in the midst of an opioid crisis, as overdose and addiction of opioids turns out to be a serious national crisis that has reduced the life expectancy of the US. With an average victim’s death hitting over 47,000 people recorded in 2017.
However, despite the alarming rate of death from opioid overdose, this problem is not grabbing the headlines from the media for health stakeholders to pay more attention and look for ways to finding lasting solutions to the anomaly.
It is worthy to note that, while many people are addicted to opioids in the form of heroin and synthetic opioids, millions of people are out there, taking an overdose of opioids in the form of pain reliever prescription for chronic pains and other related health issues. Though, opioids are used in the treatment of chronic pain, research has suggested that they may not help relieve pain in the long-term. This has posed a serious threat to public health and economic welfare, not only for the United States but other affected countries as well.
According to the Centers for Disease Control and Prevention, the total “economic burden” of only opioid misuse prescription in the US is estimated as $78.5 billion per year, inclusive of lost productivity, criminal justice involvement, healthcare cost, and addiction treatment.
This article aims to look at how we come to this point, some facts about opioids in the United States, and some useful information about opioid overdose. Read on to uncover them all.
Opioids and Substance Abuse at a Glance.
Opiates, popularly known as narcotics, are commonly prescribed for quick pain relief and sleep inducement. Originally, it is derived from poppy plant seeds or their byproducts. Opiates occur naturally in the form of opium and morphine, but most opiates are synthetic. These drugs became highly addictive because they create an intense sense of euphoria and as well as safeness, when adding it to pain-relieving properties.
Most patients with pain disorders later turn to rely on pharmaceutical opiates like oxycodone and hydrocodone; hence, they become addicted to it. However, opioid overdose has been studied to cause a number of health problems in the users, and these health issues are not limited to serious disorders, but even death. One of the prolonged effects of opioid usages is the brain’s inability to produce endorphins naturally. Endorphins are known to be the body’s natural painkillers.
Initially, around late 1990s, when opioids were becoming popular among the people, pharmaceutical companies came out to allay the fear of the people and reassure the medical community that opiate users would not become addicted to opioids prescribed for pain relief; hence, healthcare service providers started prescribing the drugs to patients at greater rates. Subsequently, this act resulted in a extensive misuse and diversion of these drugs prior to the time it was discovered that opioid prescriptions could actually be highly addictive like other opiates.
Facts about Opioid Prescription and Misuse in America.
The rates of opioid overdose in the United States started increasing in 2017 with over 47,000 citizens died due to misuse of opioids, such as heroin, prescription opioids, illicitly manufactured fentanyl (one of the powerful opioid synthetics). In the same year, this number was estimated 1.7 million and 652,000 Americans suffered from prescription opioid pain relievers and heroin use disorder respectively. The question is, how does it start?
It all starts when the body cannot properly manage and regulate pain again. In this condition, an opiate user may become addicted to the drugs, as the drugs now used to relief their pain and at the same time, create a sense of contentment and happiness in using them. Over time, even after the pains have gone, an opiate user will require more of the substance to reach the same level of high that creates happiness and contentment which they first experienced; hence, the person is already “an opiate addict.” Withdrawing from its use makes it even worse, as their bodies begin to show some unpleasant symptoms that make the user seeking more to relieve the symptoms.
From here, opioid prescription and misuse have turned out to become a public health problem in the United States with alarming rates of death on a daily basis.
Below are some facts about the opioid crisis in the United States:
- According to WQAD Digital Team’s claim of IMS Health’s market research, the number of opioid prescriptions doctors dispensed increased from 112 million to 282 million from 1992 to 2012 respectively. However, according to IQVIA, the number has declined to 236 million in 2016 and further dropped by 10.2% in 2017.
- Centers for Disease Control and Prevention, about 68% of cases of estimated 70,200 drug overdose deaths recorded in 2017 were linked to the use of opioids. This is more than six times compared to that of 1999 (including illegal opioids such as heroin and illicitly manufactured fentanyl and prescription opioids).
- According to a review, about 21 – 29% of patients with chronic pain who take opioids prescription misuse them.
- Another study also claimed that roughly 80% of heroin users initially misused prescription opioids.
- The same study also claimed that about 8 – 12% of opiate users develop an opioid use disorder.
- According to the Centers for Disease Control and Prevention, there is a 30% increase in opioid overdoses in 45 states of the United States between July 2016 to September 2017.
- In another review, opioid overdoses were seen increasing by 70% in the Midwestern region between July 2016 to September 2017.
What is been doing about it?
With over two million opioid dependants in the United States, the U.S. Department of Health and Human Services (HHS) is making efforts to tackle the opioid crisis in America by focusing on five major areas. These include:
- Promoting and enlighten people on the use of overdose-reversing drugs.
- Giving people access to treatment and recovery therapies.
- Offering support for modern research on addiction and pain.
- Promoting public health surveillance to help people understand the epidemic better.
- Enhancing better pain management practices in the country.
In furtherance to the efforts of the U.S. Department of Health and Human Services (HHS), the National Institutes of Health (NIH)’s Director Francis S. Collins in April 2018’s National Rx Drug Abuse and Heroin Summit, announced the launch of a special program referred to HEAL (Helping to End Addiction Long-term) Initiative. HEAL is an aggressive effort set up to expedite scientific solutions to address the opioid crisis in the United States.
Just because media are not paying attention to the opioid crisis in the US does not mean things are working in the medical world. With the alarming rate of opioid overdose and an increasing number of Americans abusing prescription and becoming dependent on opioids, all hands must be on deck to find a lasting solution to the current problem. While different agencies and stakeholders are not relenting on their efforts, more medical developments and approaches are still required to achieve a good result.
Autologous mesenchymal stem cell application for cartilage defect in recurrent patellar dislocation: A case report
Recurrent patellar dislocation is a repeated dislocation that follows from an initial episode of minor trauma dislocation . Conservative management gives a minimal result in re-dislocation, with persistent symptoms of anterior knee pain, instability and activity limitation. Meanwhile, there is no gold standard treatment of realignment procedures. This can further cause cartilage lesion in the patella and femoral condyle, and consequently increase the risk of re-dislocation. Mesenchymal stem cells (MSCs) have been widely explored for treating cartilage defect due to their potency of chondrogenic differentiation. We present a novel approach of treating cartilage lesions in recurrent patellar dislocation by combining of arthroscopic microfracture and autologous bone marrow derived MSCs (BM-MSCs) after Fulkerson osteotomy.
Presentation of case.
A 21-year-old male presented with left knee discomfort. Ten years ago, the patient felt discomfort on the medial side of the knee and felt his knee cap slide out laterally. The patient experienced several episodes of instability ranging from a feeling of “giving away” until a prominent lateral sliding-off of his knee cap. Anterior knee pain has also occurred during activities such as climbing stairs or exercising.
Physical examination revealed slight pain on the anterior side of the patella, but no atrophy or squinting patella. Knee range of motion (ROM) was normal when the knee cap position was normal, but was limited when it was dislocated (0–20°). Lateral subluxation of the patella was found when the knee was extended from 90° flexion position (J-sign positive), positive patellar apprehension test, with medial patella elasticity/patellar glide >2 quadrants. The Q angle, in the 90° flexed knee position, was 10°, which was still normal. The plain radiograph imaging showed no abnormality. Insall-Salvati index was 1.12. The patient was diagnosed with recurrent patellar dislocation, with suspected cartilage lesion of the left knee.
The first surgery was an arthroscopy diagnostic and distal realignment procedure (lateral retinaculum release, percutaneous medial retinaculum plication, and antero-medialization of tibia tubercle/Fulkerson osteotomy). We found articular cartilagedefects on the lateral condyle of the femur with a diameter of 3 cm (Figure. 1A), and on the postero-medial with a diameter of 2.5 cm (Figure. 1B), and the depth of both was more than 50% of the cartilage thickness. We determined that the articular defect was Grade 3 according to International Cartilage Regeneration & Joint Preservation Society (ICRS). We performed a dissection of lateral retinaculum (lateral release) (Figure. 1C) using an electrocautery, continued by incising the medial side of tibia tuberosity and detaching the patellar tendon by using an oblique osteotomy procedure on tibia tuberosity, where the fragment slide 1 cm antero-medially and fixed with two 3.5 mm (length 40 mm) partial threaded cancellous screw, followed by percutaneous plication on the medial side of the patella using non-absorbable string (Figure. 2A). Post-operative ROM was 90° flexion without any dislocation (Figure. 2B) and the position of the screws was good (Figure. 2C).
Figure 1.A. Cartilage defect on the femoral lateral condyle with a diameter of 3 cm (pointed by the arrow). B. Articular cartilage defect on posteromedial patella with a diameter of 2.5 cm (pointed by the arrow). C. Lateral retinaculum dissection/lateral release using an electrocautery (pointed by the arrow).
Figure 2.A. Percutaenous medial plication using non-absorbable string no.2. B. Post-operative anteroposterior and lateral projection of plain radiograph imaging. C. Post-operative CT scan.
One month after surgery, full ROM and weight bearing exercises were started, including knee exercise until maximum flexion was reached along with quadriceps muscle exercise. Eighteen month after that surgery, we performed an iliac crestbone marrow aspiration; arthroscopic microfracture by using an awl until 4 mm depth was reached on the site located ±3–4 mm from the articular cartilage defect on the posteromedial patella and femoral lateral condyle (Fig. 3A); and tibial tuberosity screw removal.
Figure 3.A. Arthroscopic microfracture on cartilage defect using an awl, with a depth of ±4 cm. B. The mesenchymal stem cell culture after day 22 showing fibroblast-like cell/spindle shaped cells that 100% confluent.Approximately 30 mL of bone marrow was aspirated from the posterior iliac crest. Bone marrow aspirate was diluted in phosphate-buffered saline (PBS) and centrifuged at room temperature. The buffy coat was washed and cultivated for 3–4 weeks until reaching the required amount (107 MSCs/mL) (Figure. 3B). The cells were harvested and characterized with flow cytometer. The MSCs, having negative bacteria and fungi tests, were injected intra-articularly into the left knee. Then, 2 mL HA were injected weekly for 3 weeks. Non-weight bearing exercise was conducted for 6 weeks.
Outcomes were assessed by using International Knee Documentation Committee (IKDC) score, visual analog scale (VAS) score and imaging. Baseline IKDC score was 52.9 and VAS score was 8. Nineteen months after the first surgery, IKDC score was improved to 93.1, while the VAS score decreased to 2. Six months after MSCs implantation, evaluation by MRI FSE cor T2-weighted signal (cartilage sequence) showed a significant growth of articular cartilage covering most of the defect (Figure. 4). Two years after the MSCs implantation, there was no complaint and full ROM was reached.
Figure 4.MRI FSE cor T2-weighted signal in different slice. Left image showing cartilage defect (pointed by the arrow). Right image showing cartilage growth was found in the defect (pointed by the arrow).
Recurrent patellar dislocation are uncommon problem, with recurrence rate 15%–44% after conservative management, while cartilage lesions following recurrent patellar dislocations are quite common, but still no gold standard or consensus on the management. This patient was diagnosed as chondromalacia Grade 3 Outerbridge classification and Grade 3 ICRS. One of the suitable procedures for recurrent patellar dislocation with chondromalacia, especially Grade 3 or 4, was Oblique Fulkerson-type osteotomy, with or without the release of lateral retinaculum. This distal realignment procedure could decrease patellofemoral pain by anteriorization of tibial tuberosity, decreasing articular contact pressure and at the same time medializing knee extensor mechanism. Therefore, we performed the Fulkerson-type osteotomy with lateral retinacular release, combined with percutaneous medial plication since the patient was already 21 years of age and the bone was expected to be mature so that the risk of premature physeal closure in proximal tibia can be avoided. This technique has demonstrated good results (86%), although it had a risk of tibial stress fracture in the healing process. The lateral retinacular release is an adjuvant after tibial tubercle medialization to re-center the patella. It was reported that isolated lateral retinacular release significantly gives an inferior long-term result compared to medial reefing. Percutaneous plication of medial patella procedure was indicated to build a strong construct by shortening the patellofemoral ligament, in order to prevent lateral sliding of the patella.
Treatment of articular cartilage defect remains challenging since it has limited self-healing capacity. Lesions that do not reach the subchondral zone will be unlikely to heal and usually progress to a cartilage degeneration. Limited blood supply in the cartilage and low chondrocyte metabolic activity disrupt natural healing that is supposed to fill the defect by increasing hyaline cartilage synthesis activity or stem cell mobilization from bone marrow to site of injury. The proper initial procedure for chondral lesion >4 cm2 was marrow stimulation by mosaicplasty or microfracture; and for a lesion <4 cm2 and >12 cm2 accompanied with symptoms, autologous cartilage implantation (ACI) beneath a sutured periosteal flap was promising. This procedure could not regenerate cartilage in the long term, due to loss of flap or cell suspensions. A scaffold (e.g. HA) was then used to act as an anchorage for chondrocytes adherence on cartilage defects and to promote the secretion of chondrocyte extracellular matrix. The BM-MSCs implantation could be an alternative source of the chondrocytes. Human BM-MSCs are relatively easy to isolate and to be cultured in such a condition that may retain their capability to differentiate into chondrocytes.
The MSCs effect was reported as effective as ACI and even had the advantage over ACI in terms of the number cells obtained, better proliferation capacity and less damage in the donor site. Treating large cartilage defects by using BM-MSCs showed good outcome, but the transplantation procedure was invasive. Wong et al. conducted a clinical study of the BM-MSCs intra-articular injection in combination with high tibial osteotomy (HTO) and microfracture for treating cartilage defect with varus knee. They reported that intra-articular MSCs injection improved the outcomes in the patients undergoing HTO and microfracture. Here we performed also a less invasive approach by injecting the autologous BM-MSCs intra-articularly, following the arthroscopic microfracture using an awl to penetrate the subchondral bone plate in the cartilage defects, which led to clot formation. This clot contains progenitor cells, cytokines, growth factors and pluripotent, marrow-derived mesenchymal stem cells, which produce a fibrocartilage repair with varying amounts of type-II collagen content. Cytokine within the fibrin clot will attract the injectable stem cells to the cartilage lesions.
The HA injection in this patient was aimed to suspend the MSCs and to support regenerative potency of MSCs with chondroinductive and chondroprotective potency of HA. Intraarticular injection of MSCs suspended in HA could be an alternative treatment for large cartilage defect. Supporting microfracture technique by intra-articular HA injections had a positive effect on the repair tissue formation within the chondral defect. The MRI showed that there was a growth of articular cartilage covering most of the defect even though it was not perfect as yet.
This case report demonstrated that combining Fulkerson osteotomy with the lateral retinacular release and percutaneous medial plication was effective in treating chronic patellar instability. The combination of microfracture and MSCs implantation was safe and could regenerate the articular cartilage in this patient.
Autologous micro-fragmented adipose tissue for the treatment of diffuse degenerative knee osteoarthritis: an update at 3 year follow-up
The management of chondral disease is challenging because of its intrinsic poor healing potential. Biomechanical and biological changes may lead to the loss of tissue homoeostasis, resulting in an accelerated degeneration of the articular surface, eventually leading to end-stage osteoarthritis (OA).
Conservative therapies for the treatment of knee degenerative processes, such as non-pharmacological interventions, systemic drug treatment and intra-articular therapies are used before resorting to surgery; nonetheless, they may offer only short-term benefits. Encouraging preliminary results have been reported using mesenchymal stem cells (MSCs), either alone or in association with surgery. Among the many sources of MSCs, adipose tissue has created a huge interest in the context of cartilage regeneration (Pak et al. 2016; Ruetze and Richter 2014), due to its wide availability, ease to harvest and richness in mesenchymal cell elements within the so called stromal vascular fraction (De Girolamo et al. 2016; Caplan 2008; Caplan and Correa 2011; Caplan and Dennis 2006). Moreover, MSCs from adipose tissue are characterized by marked anti-inflammatory and regenerative properties, which make them an excellent tool for regenerative medicine purposes (De Girolamo et al. 2016; Caplan 2008; Caplan and Correa 2011; Caplan and Dennis 2006). Nevertheless, preparation of autologous MSCs for injection requires ex vivo culture from a good manufacturing practice facility, which makes the process laborious and expensive (Ährlund-Richter et al. 2009; Arcidiacono et al. 2012; Sensebé et al. 2010). An increasing number of adipose tissue-derived cell isolation systems, allowing for minimal manipulation, have been developed in the last years. We previously reported the safety and feasibility of autologous micro-fragmented adipose tissue as adjuvant for the surgical treatment of diffuse degenerative chondral lesions at 1 year follow-up (Russo et al. 2017). Here we present the outcomes of the same cohort of patients evaluated at 3 year follow-up.
The original study was approved by the Ethics Committee of Verona and Rovigo – Italy (protocol n° 10,227, March 1st, 2016). An extension of the study protocol has been conceded by the same authority to evaluate the results at 3 years (protocol n° 14,505, March 14th 2018) and written informed consent was obtained from all patients.
Study design and population, surgical techniques, post-op rehabilitation protocol, safety and clinical evaluation were previously described (Russo et al. 2017). Briefly, 30 patients, affected by diffuse degenerative chondral lesions of different degrees of severity, were treated with autologous and micro-fragmented adipose tissue between 1stJanuary 2014 and 31st December 2014. Of these 30 patients, 24 (80%) also had an associated surgery (ACL/LCL reconstruction, high tibial osteotomy, meniscectomy), while six (20%) underwent arthroscopy alone. For the 3 year follow-up all the patients were re-contacted and clinically evaluated by the same clinicians.
Of the 30 patients treated with autologous micro-fragmented adipose tissue, eight also had meniscal surgery, five plate removal, three osteotomy, two ligament surgery, two microfractures, and four other surgical procedures. The remaining six had arthroscopy alone. Despite the heterogeneity of the associated surgical procedures all the patients shared the presence of chondral lesions of different degrees of severity (Russo et al. 2017).At 3 years follow-up, one patient was lost, and seven (23%) received additional treatments in the period of observation, and therefore have been considered failures. In detail, between 18 and 30 months, one patient had three injections of hyaluronic acid and the other six had multiple injections of platelet rich plasma. Background data on this subpopulation is reported in Table 1.
Table 1: Background data of the failures (n = 7)
FC femoral condyle, TP tibial plateau, PF patellofemoral.
No adverse events, lipodystrophy cases at the harvesting site nor atypical inflammatory reactions at the joint level were reported in the 3 year period for all the 29 patients.On average, the 22 patients that had no other treatments in the 3 year period (Table 2) showed that the results observed at 1 year were maintained (T36 vs. T12, p > 0.05). Moreover, 41, 55, 55 and 64% of the patients improved with respect to the 1-year follow-up in the Tegner Lysholm Knee, VAS, IKDC-subjective and total KOOS, respectively.
Table 2: Background data of the population (n = 22)
|Grade chondropathy (ICRS classification)|
FC femoral condyle, TP tibial plateau, PF patellofemoral. Compared to pre-operative values, more than 50% of the patients improved at least 20 points in all the considered scores, and, surprisingly, 55% of the patients improved at least 30 points in the VAS pain scale.
A summary of the results is reported in Figure 1.
Figure 1: Trend of functional improvements of Tegner Lysholm knee, VAS pain, IKDC subjective and total KOOS pre-operatively (white bars), at 12 (grey bars) and 36 months (black bars) after micro-fragmented adipose tissue injection. Results are expressed as mean and standard error.
The main finding of this study is that the beneficial effect of autologous micro-fragmented adipose tissue as adjuvant for the treatment of diffuse degenerative chondral lesions is maintained in the mid-term. In addition, no complications were observed in the 3 year period showing the safety profile of this procedure. No patient, including the seven patients who received additional treatments, worsened compared to the pre-operative condition.
Despite the heterogeneity of the associated surgical procedures all the patients shared the presence of chondral lesions of different degrees of severity, which may have been responsible for the impairment in function and pain.
As reported in literature, articular surface damages, especially when diffused (three compartment OA), positively correlate with a decay in the outcomes in patients who received knee surgery for other reasons (Bonasia et al. 2014; Røtterud et al. 2012; Saithna et al. 2014; Su et al. 2018; Verdonk et al. 2016). Published data shows a decline in the clinical results in the mid to long-term for arthroscopic and chondral debridement procedures in cases of initial knee OA (Su et al. 2018). Some authors assessed the effectiveness of the arthroscopic or conservative treatments in patients diagnosed with knee OA (Kellgren-Lawrence grade 2 to 4) with 5 years of follow-up, concluding that arthroscopy provided no benefit in decreasing or delaying arthroplasty and that it can relieve symptoms only up to 2 years (Su et al. 2018). The same observation has been reported for ligament reconstruction, where the short and mid to long-term benefits are inferior in patients who have cartilage lesions. In a study of a cohort of ACL-injured patients with full-thickness cartilage lesions (ICRS grade III–IV), the authors showed that ACL-injured patients with full-thickness cartilage lesions reported worse outcomes and minor improvement after ACL reconstruction compared to patients without cartilage lesions at 2–5 years follow-up, although no significant differences between the two groups at the time of ACL reconstruction were present. This means that the observed differences between the groups must have occurred during the follow-up period (Røtterud et al. 2012). Furthermore, the outcomes of osteotomy procedures in patients with diffuse degenerative knee chondropathy worsen in the mid to long-term (Bonasia et al. 2014; Saithna et al. 2014). In a study reporting the results of a case series of opening wedge distal femoral varus osteotomies for valgus lateral knee OA, it is shown that re-operation for non-arthroplasty related surgery was common due, besides others, to infection and persistence of symptoms (Saithna et al. 2014). With regard to meniscectomy, in a recently published paper it is concluded that meniscus therapy including partial meniscectomy, meniscus suture, and meniscus replacement has proven beneficial effects in long-term studies in patients without cartilage damage, supporting the hypothesis that meniscectomy increases the risk of cartilage degeneration (Verdonk et al. 2016).
Based on the aforementioned published evidences, we should have expected, in the mid-term, a decay of the outcomes. Notably, the results have been maintained with no significant differences in all the evaluated parameters with respect to the 1 year follow-up assessment. Furthermore, in line with that already observed at 1 year, the patients with lesions in more than one compartment had higher and statistically significant improvements compared to patients with lesions in only one compartment (p < 0.01). This finding supports our hypothesis of using micro-fragmented adipose tissue for the treatment of the diffuse degenerative knee pathology as an adjuvant of the surgical procedures. Indeed, the maintenance of stable results at the last follow-up leads to hypothesize a protective role of micro-fragmented adipose tissue in a further chondral degeneration.
The seven patients who received additional biological therapies in the 3-year period, were young (mean age 36.3 ± 7.3 vs. 44.7 ± 11.4), very active in sport and 6 out of 7 had a patellofemoral chondropathy. Their conditions after 1 year did not worsen, but they probably needed an additional biological treatment because of their high functional demands and the presence of the patellofemoral chondropathy, which is a negative prognostic element, even if the small number of patients does not allow for any statistical correlation.
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UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy. Hair follicle stem cells are long-lived cells in the hair follicle that are present in the skin and produce hair throughout a person’s lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases, they fail to activate, which is what causes hair loss.
The study by Heather Christofk, PhD, and William Lowry, PhD, both of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose — a form of sugar — from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can send pyruvate to their mitochondria — the part of the cell that creates energy — or convert pyruvate into another metabolite called lactate.
The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at the University of Utah, they increased lactate production genetically in the mice, which accelerated hair follicle stem cell activation, increasing the hair cycle.
The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate, and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.
“Lactate Dehydrogenase Activity Drives Hair Follicle Stem Cell Activation,” Nature Cell Biology, August 14, 2017
One of the treatments that the FDA approved for knee arthritis is a Hyalronic Acid (HA) injection, sometimes also known as Viscosupplementation. It has been incredibly successful for knee arthritis. In fact, so successful that many physicians are starting to use it on other parts of the body, like the hip and shoulder, which the FDA does not approve of.
HA, when injected, works like the fluid that naturally surrounds your joints. This fluid can be like a lubricant for your joints, and absorb shock, allowing bones that otherwise cause arthritis pain cause much less. Over time, it is even absorbed into the joint, which can cause the body to create a more stable cartilage all on its own.
The evidence for this treatment is astounding, with a systematic review of 76 trials, all of which were randomized controller trials. The review noted that HA, when injected, can benefit function, reduce pain, and can be a reliable and effective treatment for knee osteoarthritis.
On the other hand, there is PRP therapy. Platelet Rich Plasma, or PRP, which is a type of blood that has 6 to 10 times more platelets than what is normally found in blood. They even contain many growth factors, such as Epidermal Growth Factor, Connective Tissue Growth Factor, and many more. These can help heal injured parts of the body by using the bodies natural healing tools.
However, PRP is not regulated by the FDA, and devices that are used to make PRP require said approval. Aside from this, multiple studies shoe that PRP can be very effective in the treatment of tendon injuries, as well as for osteoarthritis. This treatment can even help in the reduction of pain. There are even more studies being conducted on whether it can help other things, such as hair regrowth, cardiac muscle repair, and even dermatologic rejuvenation.
So should you use HA injections, or PRP?
In many studies, PRP has bee demonstrated to work just as well, if not better than HA. HA is also only FDA approved for the knee, meaning that it is not approved or covered for the use in any other joint. Also, the risk of infection and rejection is far less while using PRP, as it is a substance that comes from your own body, and contains white blood cells, which can help fight infection.
PRP also saves money in the long run, as using HA in a joint other than the knee is not FDA approved or covered by insurance. As a result, it can cost your patient 1500$ or more. This can even be on top of various other charges, such as doctors visits, and even the injection itself. PRP, on the other hand, only costs from 800 to 1200$ out of pocket.
So PRP has been demonstrated to be just as effective, if not better, than HA injections when it comes to arthritis pain. It does not pose a risk for infection or and auto-immune reaction either, and is even far cheaper than HA. So picking which one to use should be a no-brainer.
One of the main things that causes many people cosmetic distress and low self esteem is acne scarring. Most of us have some kind of experience when it comes down to scarring, but the most embarrassing scars are the ones that are out in the open. Such as on our faces. So what can Platelet Rich Plasma do for this?
Well, both the Department of Dermatology, Venereology, and Leprosy, as well as the National Institutes of Medical Sciences have indicated that it can be used as a viable treatment for eliminating scars. One study, done by the Department of Dermatology, Venereology, and Leprosy, sought to evaluate just how effective and safe PRP therapy can be, especially when combined with microneedling. Microneedling has been a common treatment on its own for acne scars, using distilled water, for a long time.
The way that Microneedling works is that it is used to initiate collagen synthesis on the face, thus allowing the skin to heal itself. What it does is cause micro injuries to the skin of the face using small needles. However, since the needles are so small and fine, that it does not cause any serious injury. The initiation transmits electrical signals, which calls on the body to begin a healing process, by causing small inflammation and bringing growth factors to the area.
This healing process causes new blood cells to form, and thus helps to remove the scarring over time. General treatment times are known to take from just a couple of weeks up to a year in many cases. 50 patients were involved in this study, all aged 17-32, and all suffering from acne scars.
On one side of the face, they used regular distilled water combined with the microneedling procedure, and on the right they used a topical solution of PRP. After 3 treatments giving withing the time span of a 3 months, each treatment being 1 month apart, the results that used PRP was much more likely to show improvement over the distilled water group. This would be 62.2% improvement vs 45.8% respectively. This showed that PRP can have great success in managing acne scars, and helping to make them go away.
This shows that when it comes to PRP therapy, the science again shows that there is a good and significant use for it. So what is stopping you from implementing this therapy for your patients?
In popular media, the term Regenerative Medicine, or Stem Cell Therapy, are becoming buzz words. This is because the field of medicine and healthcare is expanding and advancing every day, and many new treatments for otherwise common ailments are being discovered. These conditions range from burns, joint pain, strain, and pretty much every other common ailment out there.
Many patients have given up hope with trying to find traditional medicines that work. This is why many people are flocking to try Regenerative Medicine. This is also something that many people who are into holistic healing are trying, as it is simply the body working to heal itself.
Regenerative Medicine works as it takes a sample of your own blood, bone marrow, and other tissues, and then it goes through a process in which to take out a certain material known as Platelet-Rich Plasma. This PRP is then applied to the infected area, so that your body’s own platelets can work to heal your body back to full health, without having to worry about any invasive surgeries.
A good question to ask is why our body does this do this itself. Well, this is because research has shown that by isolating them, they activate, and as a result when injected back into the body start to work harder to fix the issues, such as in a joint, or helping to relieve pain. Many patients who try it say they have gotten good results from the treatment.
Many doctors predict that this therapy will help physicians provide a more non-intrusive treatment that has fewer side effects, and can be big within the coming years. Many compare it to the invention of penicillin with how important it is. It is even growing in popularity with many physicians using training courses to help their patients, leaving many of them happier and healthier.
The entire field of orthopedics is looking for new regenerative technology that can save more patients more safely. Currently there are two contenders: Platelet-Rich Plasma and Stem Cell.
While PRP is the safest of the two, it’s really hard to dismiss the remarkable capabilities of stem cell therapy. In fact, I believe it’s the future of regenerative medicine. But not at the level it’s playing right now. Which is a totally different discussion we’ll save for another day.
The thing is… there are potential harm with stem cells. And unlike PRP, stem cell’s constituents are man-made, so things can go wrong. We’ll discuss the potential dark side of this therapy later in this article. However, I feel it’s important to highlight how good a treatment stem cell therapy is.
Quick Overview: Stem Cell Vs Platelet-Rich Plasma
Platelet-Rich Plasma is like water and nutrients that help restore (and sometimes accelerate) your body’s EXISTING healing mechanism. If your body is stuck with its healing, PRP can help. It releases growth factors and cytokines to kick start the healing. Stem cells on the other hand is not used to enhance healing, but to create new solutions to healing challenges. So it’s more for tissues that are totally lost.
Stem Cell Vs Platelet-Rich Plasma
With me? Before we proceed, let’s look at a little background of stem cells. We’ll stick to orthopedics for the sake of simplicity.
Orthopedic Stem Cell Therapy
Stem cells are naturally found in the human body and they are a fundamental part of the body’s normal healing process. Stem cells are known as ‘raw potential’ as they can be converted into any cell that the body needs. The body utilizes stem cells to substitute damaged and/or injured cells. This process allows natural healing and repair of the injured or damaged cells.
As the body gets older the amount of natural reserved stem cells starts to decline, which explains why the healing process is slower as the body gets older. Stem cell therapy resolves this shortage by injecting supplementary stem cells into the injured/damaged area of the body, which triggers the cell replacement, natural healing, and pain relief.
Stem cell therapy is a simple and quick procedure, taking about 15 minutes. Pain discomfort is often felt immediately, with the majority people reporting a significant improvement within one to two days.
With stem cell therapy the patient does not have to have any type of surgical procedure, local or general or downtime. Most of the patients experience a complete restoration of the damaged/ injured ligaments, tendons, and cartilage within about in 28 days. Stem cell therapy has been proven to be complexly safe, with no side effects reported in the US or in Europe.
The Difference Between Stem Cell Therapy and Platelet-Rich Plasma (PRP) Therapy
Often times, stem cell therapy and PRP can be confused because they have a lot in common during the healing process. The easiest way to tell the difference between the two, is PRP is removed from the patient’s own body, it goes through a scientific process and is them injected into the area being treated.
The cells used for stem cell therapy can come from a few different places; from an unviable embryo, and unviable fetal stem cells these stem cells are the most often used because the cells are unspecialized and can be made into specialized cells. As it sounds, preparing stem cells for therapy is a complex process. Stem cells are produced in a sophisticated labs by cell biologists and are typically grown over several weeks before it’s ready.
Plus, adult stem cells may be used, although it is not nearly as common yet because scientists are still working on ways to identify stem cells within the tissue of an adult human body.
Stem Cell Vs Platelet-Rich Plasma
So what’s the dark side of Stem Cell Therapy?
The obvious concern is that treatments with stem cells could be dangerous if not carefully controlled. I know we are all doing things for saving lives and helping people live longer, more happily, but the risks must also be considered.
Below are the 5 risks that stem cells carry. (which Platelet-Rich Plasma doesn’t.)
Risk of viruses: Since the stem cells are foreign bodies, if they happen to carry harmful microscopic agents, it’ll bring unnecessary complications. Especially those patients whose immune systems are weak, could be highly vulnerable diseases.
Uncontrolled growth: As I said before, stem cells are produced in a lab and grown over a period of several weeks. However, there is very tiny possibility the growth will continue uncontrolled after installing it into the patient. We pray it doesn’t happen.
Multi-tasking of cells: Stem cells are cultivated and grown into specialized cells that are designed to be doing just one thing and one thing only. But what if, in the long run, they also do other things that wasn’t in the original scope of things? Something to ponder.
That said, I still believe stem cells hold great promise. Now, I want to take this rest of the article to highlight a few of the common conditions that are found to be best for stem cell treatments.
Stem Cell Vs Platelet-Rich Plasma
Rheumatoid Arthritis is caused by inflammation of the joints as a result of an autoimmune progression. The body’s immune system attacks the joints. Patients with Rheumatoid Arthritis suffer from mild to severe pain, constant fatigue, warm, and swollen joints. This type of chronic inflammation has the potential to easily damage the joints. Therefore, treatment is concentrated on decreasing the inflammation and slowing down the progress of the condition. Stem cell therapy provides a treatment alternative that takes advantage of the healing and anti-inflammatory effects.
Osteoarthritis is joint inflammation caused by the deterioration of the cartilage that cause the bones to rub up against one another. Patients who suffer from osteoarthritis have pain, stiffness, and a decrease in their range of motion in their joints. Although, there is no cure for osteoarthritis, stem cell treatment focuses on reducing the pain reduction through medication, physical therapy, or occupational therapy. Stem cell therapy provides a treatment alternative that takes advantage of the healing and anti-inflammatory effects. While medication helps with the pain.
Shoulder injuries such as rotator cuff tears and arthritis of the shoulder joint, as well as other types shoulder pain may be responsive to stem cell therapy. Stem cells goal is to renew damaged joints.
Stem Cell Treatment for Joint Repair
Hand and elbow problems caused by arthritis of the joints is a type of deteriorating joint disease that has disabled millions of people. Definite types of wrist and elbow joint issues including certain ligamentous injuries and tendon problems may not benefit from cell therapy. It is very important that the doctor evaluate each patient to see if stem cell therapy is a viable treatment for their patients.
Stem Cell Treatment for Knee
Knee arthritis is a type of deteriorating joint disease, which affects millions of people. Most people believe there only option for pain relief and better mobility is steroid injections or surgery, including total knee replacement surgery. However, that is not the case, many people benefit greatly from stem cell therapy. Specific types of knee issues such as, ligamentous injuries and substantial meniscal injuries may not be responsive to regenerative therapy (stem cell therapy). Each case must be carefully evaluated and the orthopedist will decide what options are best for the patient, in some cases, stem cell therapy is tried even if the patient is not exactly an ideal candidate, but trying is better than just scheduling surgery.
Stem Cell Treatment for Hip
Hip arthritis is similar to knee arthritis; millions of people suffer from hip problems. Patients usually try to delay the hip replacement surgery as long as they can and try other methods such as steroid injections, which for some people do help for a short period of time. However, long tern injects can damage the tissue near the hip. While fractured hips and certain kinds of hip injuries cannot be treated with stem cell therapy, surgery is the only available option left.
Stem Cell Treatment for Joint Repair
Problems with the hands and elbow joints usually respond well to stem cell therapy. If there are problems with the ligaments and tendons, then surgery may be necessary.
Degenerative joint diseases disable millions of people. While certain types of injuries are not a good match for stem cell therapy, there are several that are a good match. Before you prescribe surgery to repair damaged or injured joints consider about stem cell therapy, and if possible give it a try first.
Fact: According to research, PRP treatments are one of the most in-demand treatments available in healthcare.
This is impressive considering the following.
PRP is not supported by the medical industry. No big pharma funding on extensive research or marketing. No medical associations lobbying to increase its awareness.
PRP is shunned by the insurance companies. No reimbursements from them. So getting patients to pay is difficult. Especially for a treatment that’s relatively “unproven” like this.
The cost of PRP treatments are actually rising. In 2006, you can get a PRP treatment for $450. Today it costs $800. The cheapest we’ve seen is $650. The prices are still robust as demand keeps up.
However, we believe the best of PRP is not even here yet. We’re just one breakthrough study away from exploding into mainstream hospitals and clinics. We see the biggest growth in Platelet-Rich Plasma happening in Asia.
Strongly based on fundamental healing theory
The growth can be attributed to PRP’s fundamental healing property. More platelets. More growth factors and cytokines. And therefore more healing. It’s as simple as that. And no one can argue this fact.
Our body’s natural healing mechanism operates with 150,000/ul-350,000/ul platelets in blood. Using Platelet-Rich Plasma means this number is amplified by 3X to 5X. How can this be not translated into better healing?
Believe it or not, the best orthopedic doctors use Platelet-Rich Plasma. And do so regularly.
PLATELET-RICH PLASMA TRENDS
PRP can be used to promote healing of injured tendons, ligaments, muscles, and joints, can be applied to various musculoskeletal problems. And they conduct regular studies to test it’s effectiveness.
One landmark study involved double-blind randomized controlled trials to see the effect of PRP on patients with chronic low back pain caused by torn discs. The study outcome says 60% of the patients felt significant improvements.
Some were cured. CURED!
Platelet-Rich Plasma Variants
So far, there are the following type of PRP variants.
Plasma Rich in Growth Factors (PRGF)
Plasma Rich in Platelets and Growth Factors (PRPGF)
Platelet-Rich Plasma (PRP); Platelet Poor Plasma (PPP)
Plasma Rich in Platelets and Rich in Leukocytes (LR-PRP)
Plasma Rich in Platelets and Poor in Leukocytes (LP-PRP)
Platelet-Rich Fibrin Matrix (PRFM)
All of them involve Plasmapherisis — the two stage centrifugation process to separate platelets from blood. However, what happen what happens after that can be different. And the industry hasn’t found it’s middle ground as to which variant to be standardized. We believe the confusion will clear up in 3-5 years.
PLATELET-RICH PLASMA TRENDS
No matter which variant you end up using, the bio-factors at play are the following:
Growth factors: TGF-B, PDGF, IGF-I,II, FGF, EGF, VEGF, ECGF
Adhesive proteins: Fibrinogen, Fibronectin, Vitronectin, Thrombospondin-1
Clotting & Anti-Clotting factors: Proteins, Antithrombin, Plasminogen, Proteases, Antiproteases
How Platelet-Rich Plasma Actually Work
Why is the treatment commonly used for wound healing and pain management? The answer is because the platelets’ main job is to aid coagulation, act as a biological glue and support stem or primary cell migration. In addition, it also helps in restoring hyaluronic acid and accelerates the synthesis of collagen and glycosaminoglycans and increases cartilage matrix.
Not only that, the platelets are delivered in a clot which means it can immediately act as a scaffold to enable the healing process. 95% of the bio-active proteins are released within 1 hour of injecting Platelet-Rich Plasma. The platelets continue to release growth factors for 7-10 days. Thus it’s recommended to re-inject PRP every 7 days.
PLATELET-RICH PLASMA TRENDS
Why are patients coughing up their hard earned money for this?
This reminds me of hundreds of thousands of PRP treatments paid from patient’s own pocket even though they’ve been paying for years to get covered by their respective insurance provider. In 2015, PRP costs were anywhere between $600 and $800 per site per treatment. And most patients go for repeated treatments. So why were they forking up their hard earned money if the treatment was not working? Weren’t there any better alternatives under the “coverage” of their insurance provider? The answer is 1) the treatment works. 2) there’s nothing else out there that’s as natural and side-effect-free as PRP.
Consider the case of osteoarthritis. 27 millions Americans are impacted by it. 33.6% of people older than 65 are victims. All of them experience gradual degeneration of cartilage and bones — they lose roughly 5% cartilage per year. Yet, our medical industry doesn’t have a fix to stop it.
However, when doctors started doing PRP treatments for their osteoarthritis patients, they found a large majority of them had no further cartilage loss.
To me, it means we should make PRP treatments the default first-line treatment for osteoarthritis across the country.
Another huge market is hair loss and cosmetic facial applications. I know there are many people who believe PRP doesn’t work for hair. Here’s what one of the Platelet-Rich Plasma studies found were the effect of the treatment on hair loss.
“Hair loss reduced and at 3 months it reached normal levels. Hair density reached a peak at 3 months (170.70 ± 37.81, P < 0.001). At 6 months and at 1 year, it was significantly increased, 156.25 ± 37.75 (P < 0.001) and 153.70 ± 39.92 (P < 0.001) respectively, comparing to baseline. Patients were satisfied with a mean result rating of 7.1 on a scale of 1-10. No remarkable adverse effects were noted.”
I’ll take that.
That’s me getting PRP for hair. ??
PLATELET-RICH PLASMA TRENDS
PRP market is expected to hit $126 million in 2016
That number looks paltry. But that’s an 180% increase over the 2009 figure of $45 million.
Consider this. Just for osteoarthritis alone, if all the 27 million Americans receive 1 PRP shot a year at a conservative $400 per treatment, it would be a market of $10 billion. And that’s one condition out of the many that Platelet-Rich Plasma injections are proven to work.
Another condition that PRP is known to work very well is Tennis Elbow. It affects on average 1% to 3% of the overall population. That number is as high as 50% among tennis players.
Do the math.
Just getting Platelet-Rich Plasma covered by insurance will unleash the market big time and will help heal millions of patients naturally, more effectively.
Oh ya, that means the insurance companies will have to pay more. Why would they?
HOWEVER, if this treatment could reduce further expensive intervention like surgery then it may actually be a blessing for the insurance guys in terms of savings. One surgery avoided by a patient through right intervention through PRP treatments will save the insurance companies at least $25,000. Now, that’s a win-win for both patients and insurance.
I believe it’s a matter of time before insurance companies start realizing their folly of not supporting this treatment.
PLATELET-RICH PLASMA TRENDS
After all is said and done, it’s still “unproven”
The problem with PRP is that it can be used for just about everything, which is a good problem to have until health care officials (and insurance companies) start realizing that people are going to misuse it.
So it’s classified as unproven. The VAST scope of the treatment calls for urgent structure and guidelines. There are some 20+ conditions where researchers have found it “helps” in one way or another. It’s a daunting task to prove its efficiency in all the areas. Nevertheless, we’ll get there.
Though we’ll need a lot of funding for that.
And yes, we need to standardize the procedure. As well as come up with optimized protocols for each conditions. Someone need to take initiative on that. We’re counting on independent doctors and medical institutions. The big pharma won’t jump in because what’s in it for them, right?
It’s so simple, you’d be an idiot to not try it.
You only need a vacuum blood harvesting tube like what we offer here, a centrifuge with adapter for the tube, pipettes and 10ml ampules of 10% calcium chloride.
The only complexity comes from not following a standard PRP system. Because the final platelet count can depend on a variety of factors. Like initial volume of blood, the technique used and relative concentration of WBC and/or RBC. As well as on the patient’s side, there are factors such as age, growth factor and WBC content.
However, concentration-wise, there’s little confusion as once a sufficiently high range is reached, more doesn’t have any adverse or enhancing effect — it saturates at a certain point. So that’s the minimum. Once you reach that, you’re good. Although the outcome is not always guaranteed to be same, with the right number of platelets, platelet activation and cytokine release, you can get a consistency in your PRP offerings.
There’s still some uncertainty over the number of injections, the timing and delivery method of Platelet-Rich Plasma. But with wide-spread adoption, some kind of structure will emerge.
Let’s hope the first glimpses of it will arrive this year.
Do you know in 2015, the world saw approximately 1 million knee arthroplasties for osteoarthritis? At $25,000 apiece, $25 billion.
How many of these patients had the good fortune of their doctor recommending PRP early on?
Yep, it’s Platelet-Rich Plasma. There has been numerous speculations about which one among the latest Platelet-Rich family was the greatest—is it the plasma or the fibrin or even latest the A-fibrin? That confusion is somewhat over now.
Platelet-products are known to facilitate angiogenesis, hemostasis, osteogenesis, and bone growth. But see, the only reason plasma can do that is because of the growth factors it carries. Let’s review the specific roles of these growth factors in the healing process.
Growth Factors In Platelet-Rich Plasma
These are growth factors that are traditionally known to have played a vital healing role in PRP. If you’re seeing your patients get better as a result of that injection you gave, these are guys you need to thank for.
Platelet-Derived Growth Factor (PDGF): Regulates cell growth and division. Especially in blood vessels. In other words, this guy is the reason the blood vessels in our body reproduces.
Transforming Growth Factor Beta(TGF-b): Responsible for overall cell proliferation, differentiation, and other functions.
Fibroblast Growth Factor (FGF): Plays a vital role in the wound healing process and embryonic development. Also behind the proliferation and differentiation of certain specialized cells and tissues.
Vascular Endothelial Growth Factor: Responsible for vasculogenesis and angiogenesis. Restores oxygen supply in cells when inadequate. It also helps create new blood vessels after injury.
Keratinocyte Growth Factor (KGF): Found in the epithelialization-phase of wound healing. In other words, it causes the formation of epithelium immediately after a wound or injury occurs.
Connective Tissue Growth Factor: Major functions in cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair.
These growth factors are what enables a Platelet-Rich product in tissue regeneration.
Platelet-Rich Plasma Rules
However, this new study suggests Platelet-Rich Plasma and it’s gelled cousin Platelet-Rich Fibrin both differ in the release of these growth factors which can significantly affect the healing outcome.
Here’s the takeaway:
“The advantage of PRP is the release of significantly higher proteins at earlier time points whereas PRF displayed a continual and steady release of growth factors over a 10-day period.”
Some argue that PRP enriched with large number of growth factors (a portion of it may even be excess) produce short-term effect and so is less desirable than a PRF whose release is slower and thus more beneficial in the long run.
That being said, PRF do have some advantage over PRP. Mainly:
It doesn’t need thrombin and anticoagulants.
It results in better healing due to its slow polymerization process.
And it helps in hemostasis.
How Platelet-Rich Plasma Differs From Platelet-Rich Fibrin
Platelet-Rich Plasma is a result of double spin method — a hard spin to separate red blood cells from everything everything else in the autologous (or whole) blood and a soft spin to separate the platelets and white blood cells. The result is Platelet-Rich Plasma (PRP), Platelet-Poor Plasma (PPP) and Red Blood Cells.
PRF is a newer method. Here after the first centrifugation, the middle layer is taken—which contains less platelets but more clotting factors. This gradually forms into a fibrin network and traps in the cytokines. It is then centrifuged in a PRF centrifuge resulting in PRF, a fibrin layer containing platelets and plasma.
What Matters In Healing
Obviously, when it comes to accelerating healing, immediate availability of growth factors and cytokines matter. So I believe PRP does a better job in this than PRF. Also the immediate release of growth factors for PRP means we can repeat the PRP injections for more healing factors just days after initial injection.
Platelet-derived products are in it’s infancy now. However, considering the huge potential benefits, there’s still a lot more research to be done. How about you? Which of these do you find beneficial?
If you’re a physician using any or both of these, do write to us and let us know of your experiences. Use the contact form here.