ISSCA Offers Stem Cells Certification at London’s Chandos House, a Royal Society of Medicine Partner
The intensive workshop to be held in the locale of one of the world’s most distinguished medical education providers
MIAMI LAKES, Florida— The International Society for Stem Cells Applications (ISSCA), a multi-disciplinary community of scientists and physicians collaborating to treat diseases and lessen human suffering through science, technology, and regenerative medicine, has announced a new stem cells certification workshop in London. The two-day workshop, will take place at London’s Chandos House. Chandos House is a partner of the Royal Society of Medicine, a global leader in postgraduate medical education.
With the workshop taking place in a prestigious locale for medical education, attendees can expect to network and learn from the industry’s most respected leaders. Physicians participating in the intensive two-day workshop will take advantage of expert reviews of stem cells biology, characterizations and regenerative properties of cells and cell products, cytokines, and growth factors.
Additionally, attendees will gain a clear understanding of laboratory processes in product validation, cryopreservation, and quality control. Facilitators will also discuss the regulatory landscape in detail with added sessions focusing on practice management and patient acquisition.
ISSCA is teaming up with London-based bioscience company Ludger (https://ludger.com) to provide expanded educational opportunities during the UK workshop. Ludger representatives will offer three additional learning sessions, adding to ISSCA’s traditional certification agenda. Ludger’s sessions include
- Chronic inflammation as a critical parameter in stem cells therapies
- Why biomarkers of acute inflammation cannot reliably measure chronic inflammation
- Glyhealth blood glycomics biomarkers for reliable measurement of CI
“To host one of our certification sessions in London in the shadows of the Royal Society of Medicine is an incredible honor,” said Benito Novas, Vice President of Public Relations for ISSCA. “We strive to offer innovative educational opportunities to practitioners in the regenerative medicine field, and we are excited to bring our renowned stem cells training certification to London’s medical community.”
To learn more about the ISSCA, its latest efforts, and upcoming events, visit https://www.issca.us/.
We live in a world overloaded with diets and eating plans that are all preaching miracle, long term results for weight loss and reducing risks of developing illnesses and diseases.
But, with so many different plans out there all claiming to produce the best results, it’s hard to know which one to recommend to your patients. The Paleo, the Atkins, the Pritikin Principle, the South Beach, WeightWatchers, The Zone Diet… the list goes on and on. Recently, many doctors are leaning more towards THE KETO DIET as a recommendation for not only their overweight patients; but patients that suffer from various illnesses and ailments.
WHAT IS A KETO DIET?
To put it simply, a ‘keto’ or ‘ketogenic’ diet is a low-carb, high-fat diet.
A reduction in carbohydrates puts the body into a metabolic state called ketosis. This is when the body produces small fuel molecules called ketones. Carbs are broken down into glucose and used for energy. So when someone deprives themselves of carbs, the body has no choice but to switch its fuel supply from glucose (blood sugar) to ketones found in body fat.
Therefore, as long as carbs are restricted, the body is constantly burning fat.
Kathleen M. Zelman, MPH, RD, LD told WebMD that a ketogenic diet is often used for losing weight, but it can help manage certain medical conditions such as epilepsy, heart disease, diabetes type 2, brain diseases and IBS.
WHAT ARE THE MAIN BENEFITS OF A KETO DIET?
Weight Loss & Appetite Suppression
The biggest benefit of the keto diet and the one most dieters are striving for is weight loss and suppression of appetite.
Typically, the body takes their fuel from our stores of glycogen, but with the reduction of carbohydrates in a keto diet, glucose levels are lowered and the body is forced to obtain its energy from body fat. This results in patients experiencing weight loss.
Food cravings and hunger is often the reason that our patients are failing at dieting. Another key reason why medical professionals have found the keto diet to be so successful is because of the effects it has on reducing cravings and tackling hunger.
Studies have proven that participants that follow a low-carb diet have reported a decrease in appetite and cravings compared to individuals following a low-fat diet. This is possibly down to high-fat foods slowing down the process of gastric emptying. Food that is high in fat passes through the gut at a much slower pace, leaviing the individual feeling satisfied for longer.
Diabetes Type 2
Diabetes Type 2 is triggered by spikes occurring in the patient’s blood sugar levels. Insulin is used to regulate and control these spikes. When a patient with type 2 diabetes follows a keto diet, the amount of glucose they are consuming dramatically decreases due to the lower intake of carbohydrates.
So the lower intake of glucose found in high carb food = the lower intake of insulin.
A study of 21 overweight men with type 2 diabetes who were put on a keto diet showed that most participants saw a reduction in their insulin medication or were taken off diabetes medication completely as a result of controlling their glucose levels by following a keto diet.
A keto diet has been used to treat epilepsy since the 1920s and during a recent study, seventy percent of epileptic patients have reported less and more controlled seizures and a reduction in their medication since implementing a keto diet.
Epileptic seizures occur when a network of neurons fire unexpectedly due to the overexcitement of brain cells releasing neurotransmitters, like glutamate. The brain is then not able to suppress the spread of excitability like in non-epileptic people using inhibitory neurotransmitters like gamma-aminobutyric acid, or GABA.
What a keto diet can do to control seizures is to reduce the amount of glutamate in the brain and enhance the synthesis of GABA.
Alzheimer’s Disease & Dementia
A ketogenic diet can contribute towards keeping the brain young and healthy and reduce the risk of developing degenerative brain diseases such as Alzheimer’s disease and dementia.
Findings from a study found that keto diets can protect neurovascular function against cognitive decline by clearing out beta-amyloid protein in the brain. Beta-amyloid creates toxic plaques that interfere with neuronal signaling that results in Alzheimer’s disease and dementia. Improvements to blood flow to the brain, which contributes to healthy cognitive function, were also noted.
IBS & Other Gastronomical Conditions
Fifteen percent of the general population claim to suffer from IBS. It is one of the most common complaints taken to doctors. A lot of research has been undertaken in recent years around the effect that carbohydrates have on the gastrointestinal system.
Studies have found that when sufferers consume carbohydrates, they tend to ferment in the small intestine and causes gas and bloating. For IBS sufferers, carbs are poorly absorbed by the gut wall, causing fluid to remain in the intestinal space, resulting in diarrhea.
Therefore, when IBS sufferers follow a keto diet and reduce their intake of carbohydrates, they report significant improvements to their condition.
All these amazing results from consuming low-carb, high-fat foods sounds promising, right?
Medical professions at Harvard Medical School are urging medical professionals to be wary of recommending the keto diet to their patients. They have identified numerous risks associated with following a ketogenic diet.
Not only is the body being deprived of an essential food group – carbohydrates, but a keto diet is typically high in saturated fat. High levels of saturated fat can lead to high cholesterol and heart disease.
Other risks they have been identified with following a keto diet is:
A deficiency in micronutrients including selenium, magnesium, and vitamins B and C which are found in most of the fruit and vegetables that are restricted in a keto diet.
Liver problems due to the amount of fat the body needs to metabolize. This can cause existing liver problems to worsen.
Kidney problems due to the amount of protein the body needs to metabolize. A keto diet can put strain on the kidneys and make exisitng conditions worse.
Constipation. The keto diet is low in fibrous foods like grains and legumes. The digestive system relies on a steady flow of fiber to break down foods and get rid of body waste.
“The Keto Flu” is a term for the mood swings, body aches and brain fuzz that people experience when following a keto diet. The brain needs glucose to function and when it is deprived of this, it can cause irritability and tiredness.
We want to know your thoughts and opinions on the Keto Diet!
Have you ever recommended the keto diet to your patients? Do you see the benefits happening in your patients? Is it dangerous?
JAMES P. ALLISON, PhD
Chair, department of immunology, and director.
Immunotherapy Platform, MD Anderson Cancer Center
Losing his mother to lymphoma and two uncles to melanoma and lung cancer taught James P. Alli- son, PhD, a difficult lesson at an early age. “My mother was treated with radiation and my uncle, who had lung cancer, was treated with chemotherapy. I saw the ravages of those treatments, which ultimately were unsuccessful,” he says.
Allison knew he wanted to work in cancer research, developing more effective and less toxic therapies. An undergraduate course at the University of Texas at Austin sparked his interest in T cells—warrior cells of the immune system that defend the body against infections and cancer.
The next step, he says, was to pre vent the brakes from engaging—“to give the T cells time to keep going and eliminate the tumors.” Allison’s work led to the development of drugs called checkpoint blockade antibodies, including ipilimumab (Yervoy) for melanoma. “When we started this work, the median life expectancy with metastatic melanoma was 11 months, and no drug had ever changed that,” he says. Among people treated with Yervoy, more than 20% are still alive three years later, and some have survived 10 years.
New drugs targeting another off-switch, PD-1, have since been developed to treat cancers of the head and neck, lung, kidney, and bladder, among others. Now Allison’s lab is studying different combinations of checkpoint blockades to see which patients will respond best to them. “I don’t think these approaches are going to replace any. of the traditional therapies,” he says, but, “I think that soon, immunotherapy is going to be part of every successful cancer therapy.”
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.