TUESDAY, 27 FEBRUARY 2018 / PUBLISHED IN BLOG

Although they can perform surgeries, osteopathic physicians try to avoid doing so whenever possible. Because of this, PRP seems to be an excellent fit for their practice. Since Osteopathy was built on the idea of self-healing, PRP seems to be a perfect fit.

The Current State of PRP Research

A while ago, PRP research was reviewed by The Journal Of The American Osteopathic Association, which concluded that more studies and evidence are needed to make a solid statement on its efficacy. Later, a case study was filed showcasing an 18-year-old high school football player who suffered from a sports injury. The case study showed that the muscle injury healed rapidly under PRP therapy. Although PRP is not yet universally acclaimed, it doesn’t mean Osteopathic Physicians can’t learn a lot or benefit from its use in their practice.

How Osteopathic Physicians Can Benefit From PRP

It’s Holistic

Osteopathic Physicians prefer to treat the patient rather than just treating a disease or its symptoms, making PRP a great fit. PRP works by using the body’s own resources and mechanics to help it heal itself over time. Instead of merely addressing symptoms like many conventional medicines do, it tackles the problem directly.

For example, there are cases where PRP therapy has taken the place of surgery and medication. Female patients have revived their sex drive after being treated for incontinence. While PRP therapy was initially pushed by allopathic doctors, it works wonders in Osteopathic medicine and can become a key treatment method for Osteopathic physicians.

Musculoskeletal Issues

In many practices, musculoskeletal pain is a common issue for Osteopathic Physicians. PRP is quickly becoming a primary treatment for these kinds of problems. For instance, many researchers believe PRP should be the main choice for patients suffering from knee meniscus issues.

In 2016, University of Missouri Doctor Patrick Smith published an FDA-sanctioned double-blind randomized placebo-controlled clinical trial on PRP. These trials are considered the gold standard in research. The study concluded that PRP provides safe and notable benefits for people suffering from knee osteoarthritis.

The Vast Potential of PRP

The third and most important reason why all physicians, including Osteopathic Physicians, should start using PRP therapy is its wide scope. Since PRP is simple and common, it’s safe to say that if PRP works on knee joints and tendons, it likely works on other tendons, joints, bones, and muscles. PRP will soon be a commonplace treatment for nearly all musculoskeletal diseases.

This means PRP has near limitless potential. This is especially important for Osteopathic Physicians because if a patient has a wrist problem, the main issue might appear further down the arm. Multiple PRP injections in various areas can not only heal the issue but also enhance other traditional methods used. This will help restore balance to the body and give full functionality back to the patient.

Success Stories and Expert Opinions

American Academy of Regenerative Medicine Doctor Peter Lewis has administered over 100,000 PRP injections to over 12,000 patients. He claims that more than 80% of his patients who have undergone PRP therapy have had fantastic results. Even patients who were candidates for surgery have benefited from PRP.

Are PRP Treatments FDA Approved?

As of this year, PRP treatments are not yet subject to FDA approval. This is because all treatments are performed on the same day as the extraction and use only materials already inside the patient’s body. Therefore, PRP therapy falls within the scope of the FDA Code of Federal Regulation title 21, part 1270, 1271.1, making it exempt from needing approval.

TUESDAY, 30 JANUARY 2018 / PUBLISHED IN BLOG

Regenerative medicine is the exciting cutting-edge “medicine of the future” which holds the hope and promise of efficacy centered around the ability of human tissue to be repaired, replaced, and healed (regenerated) once human tissues and organs are damaged or diseased. Regenerative therapies aid and supplement the natural healing mechanisms of the body. These therapies often employ the activation of stem cells to stimulate the renewal of tissue damaged by injury, disease, or age. The rapid expansion of scientific knowledge offers great promise for continuing advances in this field of medicine, which holds vast potential to improve the quality of human life.

What are Stem Cells?

Stem cells are the basic building blocks of life. They are unspecialized cells that can produce more stem cells through mitosis or differentiate into specialized cells that carry out specific functions in the body. Stem cells are found throughout the body’s tissues, organs, and systems, although usually in small quantities in adults.

What are Hematopoietic Stem Cells?

Hematopoietic stem cells (HSCs) can give rise to all types of blood cells, including red blood cells, white blood cells, and platelets. They are particularly useful in the treatment of blood-related diseases and conditions.

What are Mesenchymal Stem Cells?

Mesenchymal Stem Cells (MSCs) are multipotent stromal cells that are non-blood-forming stem cells and can differentiate into a variety of cell types, including muscle, bone, cartilage, and fat cells.

When introduced into a patient’s body, MSCs can repair or replace damaged or degenerating tissue by communicating with the surrounding cells, causing a cellular cascade of healing (paracrine signaling).

The History and Potential of MSCs

Historically, the term MSC was coined in the late ’80s by the biomedical research authority, Dr. Arnold Caplan of Case Western Reserve. The acronym has recently been redefined by Caplan to “Medicinal Signaling Cell” since these cells secrete powerful bioactive molecules involved in cellular signaling and regeneration. Caplan now describes MSCs as a “multisite-regulatory dispensary” (Natural Drug Store).

The production of MSCs in the human body can be precipitated by bioactive placental tissues containing Growth Factors, Cytokines, and other powerful bioactive agents which trigger cell signaling.

The remarkable ability of MSCs makes them irreplaceable in medical treatments.

Accessible Sources of Stem Cells

Stem cells can be extracted from various parts of the body. They have been extracted from bone marrow and adipose tissue for a few decades. More recently, birth tissues from live births, including umbilical cord blood, cord tissue with Wharton’s Jelly, and amniotic membrane tissue, have been found to be a rich source of both HSCs and MSCs. These tissues precipitate target tissue production of MSCs through paracrine signaling. Growth Factors, Cytokines, Exosomes, and micro-RNA from birth tissues give rise to stem cells in this way. These cells, as well as MSCs contained in Wharton’s Jelly, tend to be more fit than adult stem cells.

Wharton’s Jelly

Wharton’s jelly is a gelatinous substance found in the umbilical cord, which is rich in stem cells. Studies have shown that mesenchymal stem cells (MSCs) have low immunogenicity. Human umbilical cord Wharton’s jelly provides a new source for MSCs that are highly proliferative and have multi-differentiation potential. Wharton’s Jelly Cells (WJCs) express MSC markers but low levels of human leukocyte antigen (HLA)-ABC and no HLA-DR. WJCs have low functional immunogenicity, and therefore recipient rejection has not been documented.

Advanced Regenerative Medicine

Advanced Regenerative Medicine involves the use of regenerative biomolecules, tissue engineering, and stem cells to treat diseased or injured tissues.

Exploring the Power of Platelet-Rich Plasma (PRP) in Regenerative Medicine

WEDNESDAY, 14 MARCH 2018 / PUBLISHED IN BLOG

We have been in the regenerative medicine specialty for about 8 years. Like pretty much everyone, we started by using Platelet-Rich Plasma (PRP). We learned about it, were fascinated by it, and treated our patients with it. Patients loved it, and so did we.

The Versatility of PRP

PRP, if obtained and used correctly, is a very powerful tool to implement in any medical practice. It is especially useful for treating the elderly, osteoarthritis, wear and tear of tendons and ligaments, and loss of vitality. PRP is also frequently used in plastic and reconstructive surgery for wound care, scar improvement, and overall rejuvenation of the skin.

How Does PRP Work?

We are all familiar with platelets. They have significant power and influence over tissue regeneration. By concentrating them in a blood sample, we can obtain signaling proteins, cytokines, and growth factors. Adding white blood cells to the mix creates what is called L-PRP (leukocyte-rich PRP), making that “soup” even more potent.

Activating PRP for Maximum Benefits

To harness the power of these bioactive substances, we need to coax the cells into releasing them. Normally, platelets get activated by the addition of calcium or by contact with collagen. However, several studies have demonstrated the influence of low-intensity laser on the activity of some cells. This effect is called “Photobiomodulation.”

Understanding Photobiomodulation

Photobiomodulation is a form of light therapy that uses non-ionizing light sources, like LEDs or Helium-Neon lasers, to produce photochemical events at various biological scales. It has been demonstrated that this light interacts with the enzyme Cytochrome C oxidase, which is crucial in mitochondrial processes.

The Impact of Low-Level Laser Therapy

Several scientists studied this light and its effects on cellular cultures. They found that cells proliferate more when exposed to low-level laser and showed increased viability. We compared the levels of cytokines and growth factors in irradiated and non-irradiated samples. Sure enough, some growth factors even tripled in concentration after laser exposure. The famous Interleukin 10, an anti-inflammatory protein, doubled its levels, and endorphins were released in high levels.

Benefits of Photobiomodulation

The photobiomodulation process provides extraordinary benefits in pain management, inflammation reduction, immunomodulation, and promotion of wound healing and tissue regeneration. It plays a fundamental part in our protocols.

Conclusion

Isn’t it all amazing? The potential of PRP and photobiomodulation in regenerative medicine continues to astonish us. We will see you in the next blog. Keep your cells healthy!

Introduction

The International Federation of Adipose Therapeutics and Sciences (IFATS) appreciates this opportunity to submit the following comments to supplement its earlier written comments and recent testimony at the September 12-13, 2016 Public Hearing on the 2014-2015 Draft HCT/P Guidances concerning: a) Minimal Manipulation; b) Same Surgical Procedure; c) Adipose Tissue; and d) Homologous Use.

IFATS Overview

International Federation of Adipose Therapeutics and Sciences (IFATS)
45 Lyme Road – Suite 304
Hanover, NH 03755 USA
Tel: 1-603-643-2325, Fax: 1-603-643-1444

Date: September 26, 2016

Addressed to:
Division of Dockets Management (HFA–305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Re: FDA-2014-D-1856 – Comments to 2014-2015 Draft Guidance regarding:

• Docket FDA-2014-D-1584: “Same Surgical Procedure Exception under 21 CFR 1271.15(b): Questions and Answers Regarding the Scope of the Exception; Draft Guidance for Industry”
• Docket FDA-2014-D-1696: “Minimal Manipulation of Human Cells, Tissues, and Cellular and Tissue-Based Products; Draft Guidance for Industry and Food and Drug Administration Staff”
• Docket FDA-2014-D-1856: “Human Cells, Tissues, and Cellular and Tissue-Based Products from Adipose Tissue: Regulatory Considerations; Draft Guidance for Industry”
• Docket FDA-2015-D-3581: “Homologous Use of Human Cells, Tissues, and Cellular and Tissue-Based Products; Draft Guidance for Industry and FDA Staff”

Commitment to Advancing Adipose-Based Therapies

IFATS is committed to the responsible advancement of the science and translation of new adipose therapies, ensuring patient safety. Founded in 2003 by pioneering adipose stem cell biologists and clinician–scientists, IFATS aims to advance the science of adipose tissue biology and its clinical translation to therapeutic applications.

IFATS’s Global Influence and Expertise

Membership now spans 40 countries across North America, Europe, Africa, the Middle East, Asia, Australia, and Central and South America. It includes basic scientists, translational researchers, clinicians, and regulatory and biotech representatives. IFATS is aligned with prestigious journals, Stem Cells and Stem Cells Translational Medicine, and has contributed to defining adipose-derived cells in the publication Cytotherapy.

Review of FDA Draft Guidances

Drawing on this expertise, IFATS has reviewed the 4 draft guidances with great care. It respectfully requests the FDA to reconsider and modify the 4 draft HCT/P guidances as follows:

Recommendations

Recommendation #1: Cell-Based Risks

Interpret and evaluate an HCT/P’s homologous use and minimal manipulation based on its manufacturer’s intended use in the patient.

Recommendation #2: Provider-Based Risks

Reduce provider-created risks by targeting provider behavior.

Recommendation #3: Recognize Structural and Nonstructural Functions

Recognize that adipose HCT/Ps have both structural and nonstructural functions, and regulate based on its manufacturer’s intended use in the patient.

Recommendation #4: Revise Evaluation of Minimal Manipulation and Homologous Use

Revise the evaluation of minimal manipulation and homologous use as they pertain to particular applications of adipose tissue.

Conclusion

IFATS is committed to collaborating with the FDA to meet the challenges of regulating HCT/P therapies. We respectfully request a meeting with FDA representatives to discuss these issues and others related to the advancement and regulation of adipose-based therapies.

Respectfully submitted on behalf of IFATS,

Adam J. Katz, MD, FACS
Chair, IFATS Regulatory Affairs Committee & IFATS Co-Founder
University of Florida College of Medicine
Professor
Director of Plastic Surgery Research, Laboratory of BioInnovation and Translational Therapeutics
Division of Plastic Surgery, Department of Surgery

IFATS Board of Directors

• Bruce Bunnell, PhD – Tulane University / United States
• Louis Casteilla, PhD – University of Toulouse / France
• Sydney Coleman, MD – New York & Pittsburgh Universities / United States
• Julie Fradette, PhD – Lavalle University / Canada
• William Futrell, MD – Founders’ Board, University of Pittsburgh / United States
• Marco Helder, PhD – VU University Medical Center Amsterdam / The Netherlands
• Adam J. Katz, MD, FACS – Founders’ Board, University of Florida / United States
• Ramon Llull, MD, PhD – Founders’ Board, University of Barcelona / Spain
• Kacey Marra, PhD – University of Pittsburgh / United States
• Ricardo Rodriguez, MD – President (2016), Private Practice / Johns Hopkins / United States
• Peter Rubin, MD, FACS – Chair, Founders’ Board, Chairman of the Board, University of Pittsburgh / United States
• Stuart K. Williams, PhD – University of Louisville / United States

Members-at-Large

• Jeff Gimble, MD, PhD – Pennington Biomedical / United States
• Keith March, MD, PhD – Indiana University / United States

IFATS Recommendations for FDA Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products

Introduction

IFATS recognizes the FDA’s challenge in developing regulations that fulfill the agency’s dual and interrelated responsibilities of protecting patients while promoting innovation. Although these are complementary rather than competing objectives, they are often difficult to pursue simultaneously. The FDA’s 3-tiered, risk-based §§ 361 – 351 framework balances these concerns by making the degree of regulatory oversight proportionate to the degree of an HCT/P therapy’s risk.

Key Regulatory Concepts

The concepts of homologous use and minimal manipulation are key determinants of whether an HCT/P will be classified as a § 361 product (which does not need premarket approval) or a § 351 drug, device, and/or biological product (which requires formal premarket approval). The applicability of § 351’s “same surgical procedure” exception also turns on homologous use and minimal manipulation.

Challenges for Manufacturer-Clinicians

For most manufacturer-clinicians, § 351 categorization raises insurmountable obstacles due to the time and expense of obtaining premarket approval. In such cases, § 351 classification effectively prohibits access to safe and effective HCT/P therapies, even when those therapies involve a patient’s own cells and/or can deliver superior results with reduced risks. At the same time, § 351 oversight is essential for therapies that pose greater risks due to the HCT/P’s characteristics, mechanism(s) of action, and circumstances of use.

Addressing Provider Misconduct

A second type of risk involves rogue clinicians offering false promises in the form of unproven therapies performed with few safeguards and less training. Provider misconduct is not unique to HCT/P therapies; it pervades all areas of medical practice. Nevertheless, IFATS shares the FDA’s alarm over such practices in the context of HCT/Ps and is equally determined to curtail them. Effective regulation of HCT/P-related risks must recognize and respond to their multivariate causes. Put simply:

• Sections 351 and 361 appropriately attempt to regulate HCT/P therapies proportionate to the risks of unpredictable and/or unsafe cell behavior.
• However, the risks of untrained providers misusing HCT/P therapies are caused by providers misbehaving, not cells misbehaving.

Comprehensive Risk Management Strategy

Interpretive guidance that restricts the definition and application of HCT/P terminology can only go so far in restricting provider-based risks. Additionally, restrictive, inaccurate, or imprecise definitions and interpretations carry their own risks of restricting access to therapies and a patient’s right to evaluate risk through the process of informed consent. Therefore, IFATS recommends that the FDA adopt an overall two-part strategy that focuses on both categories of HCT/P risks: those relating to cell behavior and those that pertain to provider behavior.

Recommendations

Recommendation #1 – Cell-Based Risks

Interpret and evaluate an HCT/P’s homologous use and minimal manipulation based on its manufacturer’s intended use in the patient. Interpretive guidance should predicate each definition on the functions and/or characteristics of the specific composition (i.e., cell type(s) and/or matrix or other component(s)) that are involved in, and/or relevant to, the manufacturer-clinician’s intended use in the patient.

Recommendation #2 – Provider-Based Risks

To reduce provider-created risks, the FDA should target provider behavior by collaborating with IFATS and comparable organizations to draw on and supplement existing federal and state methods of certification, registration, and similar measures.

Detailed Explanation of Recommendations

Recommendation #1 – Cell-Based Risks

The four draft guidances on homologous use, minimal manipulation, same surgical procedure, and adipose tissue individually and collectively intend to “improve stakeholders’ understanding” of 21 CFR 1271 by clarifying the FDA’s interpretation of homologous use and minimal manipulation. As demonstrated by the initial round of public comments and the ensuing public hearing on September 12 and 13, 2016, the draft guidance documents have not clarified applicable regulations. They have instead compounded the difficulty of understanding and complying with them. The drafts’ introduction of new definitional inaccuracies has also amplified rather than reduced patient risk.

IFATS respectfully requests the agency to clarify the definitions and application of homologous use and minimal manipulation by interpreting each as referring to the characteristics of the specific cell type(s) and/or the matrix or other component(s) that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Homologous Use Definition:

21 CFR 1271.3(c): Homologous use means the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function or functions in the recipient as in the donor.

Recommended Guidance:

As used in this section, “performs the same basic function or functions in the recipient as in the donor” shall be interpreted as referring to one or more of the functions of the specific composition of the therapeutic/product, reflecting the specific cell type(s) and/or the specific matrix or other component(s) in the donor tissue that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Minimal Manipulation Definition:

21 CFR 1271.3(f) Minimal manipulation means:

• For structural tissue, processing that does not alter the original relevant characteristics of the tissue relating to the tissue’s utility for reconstruction, repair, or replacement;
• For cells or nonstructural tissues, processing that does not alter the relevant biological characteristics of cells.

Recommended Guidance:

As used in this section, “relevant” characteristics shall be interpreted to mean the characteristics of the specific cell type(s) and/or the specific matrix or other component(s) in the donor tissue that are involved in, and/or relevant to, the manufacturer’s intended use in the patient.

Rationale:

Incorporating and relying on the manufacturer’s intended use harmonizes the interpretation and definition of homologous use and minimal manipulation with statutory directives to predicate the regulation of drugs, devices, and biologics on the manufacturer’s intended use. Defining relevant characteristics in terms of “the characteristics of specific cell type(s) and/or the matrix or other component(s) in the donor tissue that are involved in, and/or relevant to the manufacturer’s intended use in the patient” promotes patient safety by insisting on a reasonable and scientifically supportable rationale for using an HCT/P for a particular mechanism of action. This clarification balances the FDA’s dual responsibilities of protecting patients from undue safety risks while promoting the ongoing availability and continued development of HCT/P therapies.

Example of Non-Homologous Use:

Decellularized adipose matrix used to accomplish the manufacturer’s intended use of a particular metabolic or systemic effect in the patient (e.g., reducing insulin levels in a diabetic patient) is non-homologous because decellularized matrix is not relevant to metabolic or systemic activity.

Conclusion

Adopting this two-part strategy can control risk more comprehensively—and therefore more effectively—in furtherance of the FDA’s dual and interrelated obligations of protecting patients and promoting the availability of HCT/P therapies.

Introduction to FDA Regulations and IFATS Recognition

IFATS acknowledges the FDA’s dual role in patient protection and innovation promotion within the HCT/P sector. Balancing these objectives is crucial yet challenging.

Understanding the FDA’s Risk-Based Framework

The FDA’s § 361 – § 351 framework categorizes HCT/P therapies based on risk levels, influenced by concepts like homologous use and minimal manipulation.

Impact of Regulatory Classification on Access to HCT/P Therapies

Homologous use and minimal manipulation determine whether an HCT/P falls under § 361 (no premarket approval needed) or § 351 (requires premarket approval), affecting accessibility and innovation.

Provider Misconduct Risks in HCT/P Therapies

Rogue clinicians offering unproven therapies pose significant risks. Addressing provider behavior is essential for patient safety and regulatory efficacy.

IFATS Recommendations for Risk Mitigation

Recommendation #1 – Cell-Based Risks: Interpreting Homologous Use and Minimal Manipulation

IFATS proposes clarifying homologous use and minimal manipulation definitions based on manufacturer-intended use, enhancing regulatory clarity and patient safety.

Recommendation #2 – Provider-Based Risks: Targeting Provider Behavior

Collaboration with IFATS and other bodies to enhance certification and monitoring mechanisms can mitigate risks associated with provider misconduct effectively.

Recommendation #3 – Regulatory Scope for Adipose HCT/Ps

Expanding the definition of adipose tissue to include both structural and nonstructural functions aligns with biological accuracy and regulatory intent.

Conclusion: Enhancing Patient Safety and Access to HCT/P Therapies

IFATS urges the FDA to adopt a comprehensive strategy that addresses both cell-based and provider-based risks to uphold patient safety and foster innovation in HCT/P therapies.

Regulating an HCT/P’s Risks Based on Manufacturer’s Intended Use

Regulating the risks of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) is crucially tied to their intended use and mechanisms of action in patients. This ensures effective regulatory oversight and evaluation.

Regulatory Framework: §§ 351-361

The regulatory oversight of HCT/Ps under §§ 351-361 hinges on assessing the product’s risk level. Central to this determination are the criteria of homologous use and minimal manipulation.

Homologous Use Defined (21 CFR 1271.3(c))

Homologous use is defined as the repair, reconstruction, replacement, or supplementation of a recipient’s cells or tissues with an HCT/P that performs the same basic function as in the donor.

Minimal Manipulation Criteria (21 CFR 1271.3(f))

Minimal manipulation of structural tissue involves processing that preserves the tissue’s original characteristics essential for its utility in repair, reconstruction, or replacement. For nonstructural tissues, it preserves relevant biological characteristics.

Impact on Adipose Tissue

The classification of adipose tissue as exclusively structural neglects its nonstructural functions, limiting evaluation under § 361 criteria and obstructing risk assessment.

Same Surgical Procedure Exception

The § 351 “same surgical procedure” exception applies only to HCT/Ps meeting homologous use and minimal manipulation criteria, impacting nonstructural adipose applications.

Recommendation #4: Revising Evaluation Criteria

IFATS urges the FDA to reconsider specific adipose tissue applications concerning homologous use and minimal manipulation criteria.

Example A: Decellularizing Adipose Tissue

Decellularization of adipose tissue for structural use should be recognized as minimal manipulation under §§ 351 and 361 guidelines.

Example B: Structural Use of Fat in Breast Surgery

Applying adipose tissue for breast augmentation should be considered homologous use due to its structural function in restoring form and shape.

Example C: Stromal Vascular Fraction (SVF) for Nonstructural Use

SVF extraction from adipose tissue retains nonstructural components crucial for nonstructural applications, meeting minimal manipulation and homologous use criteria.

Conclusion and Call to Action

IFATS requests the FDA to amend draft guidance on HCT/Ps to align with scientific understanding and clinical practices of adipose tissue applications.

References
 

1. Bourin P, Bunnell  BA,  Casteilla  L,  Dominici  M,  Katz  AJ,  March  KL,  Redl  H,  Rubin  JP, Yoshimura K, Gimble Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: A joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the International Society for Cellular Therapy (ISCT). Cytotherapy. 2013;15:641-648
2. Diaz-Flores L, Gutierrez R, Madrid JF, Varela H, Valladares F, Acosta E, Martin-Vasallo P, Diaz-Flores L, Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol. 2009;24:909-969
3. Gimble The function of adipocytes in the bone marrow stroma. The New Biologist. 1990;2:304-312
4. Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin  during   caloric   restriction.   Cell   metabolism. 2014;20:368-375
5. Meunier P, Aaron J, Edouard C, VlGNON Osteoporosis and the replacement of cell populations of the marrow by adipose tissue: A quantitative study of 84 iliac bone biopsies. Clinical orthopaedics and related research. 1971;80:147-154
6. N. Über die wiederanheilung vollstädig vom körper getrennter, die ganze fettschicht en- thaltender hautstucke. Zbl f Chir 1893;30:16-17
7. Hollander E, Joseph Cosmetic surgery. Handbuch der  Kosmetik.  Leipzig,  Germany: Veriag von Velt. 1912;688
8. Miller Cannula implants and review of implantation technics in esthetic surgery: In two parts. Oak Press; 1926.
9. Gimble JM Fat circadian biology. Journal of applied physiology. 2009;107:1629-1637
10. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds Identification and expression cloning of a leptin receptor, ob-r. Cell. 1995;83:1263-1271
11. Salgado AJ,  Gimble    Secretome  of  mesenchymal  stem/stromal  cells  in  regenerative  medicine.

Biochimie. 2013;95:2195

12. Salgado AJ, Reis RL, Sousa N, Gimble Adipose tissue derived stem cells secretome: Soluble factors and their roles in regenerative medicine. Curr Stem Cell Res Ther. 2009
13. Khan M, Joseph Adipose tissue and adipokines: The association with and application of adipokines in obesity. Scientifica. 2014;2014
14. Vicennati V, Garelli S, Rinaldi E, Di Dalmazi G, Pagotto U, Pasquali Cross-talk between

adipose tissue and the hpa axis in obesity and overt hypercortisolemic states. Hormone molecular biology and clinical investigation. 2014;17:63-77

15. Kargi AY, Iacobellis Adipose tissue  and  adrenal  glands:  Novel  pathophysiological mechanisms and clinical applications. International journal of endocrinology. 2014;2014
16. Maïmoun L, Georgopoulos NA, Sultan Endocrine disorders in adolescent and young female athletes: Impact on growth, menstrual cycles, and bone mass acquisition. The Journal of Clinical Endocrinology

& Metabolism. 2014;99:4037-4050

17. McIntosh K, Zvonic S, Garrett S, Mitchell JB, Floyd ZE, Hammill L, Kloster A, Di Halvorsen Y, Ting JP,

Storms RW. The immunogenicity of human adipose‐derived cells: Temporal changes in vitro. Stem cells. 2006;24:1246-1253

18. McIntosh KR,  Frazier  T,  Rowan  BG,  Gimble    Evolution  and  future   prospects   of adipose- derived immunomodulatory cell therapeutics. Expert review of clinical immunology. 2013;9:175-184
19. McIntosh KR,   Lopez   MJ,  Borneman  JN,  Spencer  ND,  Anderson  PA,   Gimble    Immunogenicity of allogeneic adipose-derived stem cells in a rat spinal fusion model. Tissue Engineering Part A. 2009;15:2677-2686
20. Mitchell JB, McIntosh K, Zvonic S, Garrett S, Floyd ZE, Kloster A, Di Halvorsen Y, Storms RW, Goh B, Kilroy G. Immunophenotype of human adipose‐derived cells: Temporal changes    in      stromal‐associated and  stem   cell–associated    markers.   Stem   cells. 2006;24:376-385

21. Gimble JM, Dorheim MA, Cheng Q, Medina K, Wang CS, Jones R, Koren E, Pietrangeli C, Kincade Adipogenesis in a murine bone marrow stromal cell line capable of supporting b lineage lymphocyte growth and proliferation: Biochemical and molecular characterization. European journal of immunology. 1990;20:379-387
22. Frazier TP, McLachlan JB, Gimble JM, Tucker HA, Rowan Human adipose-derived stromal/stem cells induce functional cd4+ cd25+ foxp3+ cd127− regulatory t cells under low oxygen culture conditions.  Stem cells and development. 2014;23:968-977

23. Frazier TP, Gimble JM, Kheterpal I, Rowan Impact of low oxygen on the secretome of human adipose- derived stromal/stem cell primary cultures. Biochimie. 2013;95:2286-2296
24. Miranville A, Heeschen C, Sengenes C, Curat C, Busse R, Bouloumie Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation. 2004;110:349-355
25. Rehman J, Traktuev D, Li J, Merfeld-Clauss S, Temm-Grove CJ,  Bovenkerk  JE,  Pell  CL, Johnstone BH, Considine RV, March Secretion of angiogenic and antiapoptotic factors by human adipose stromal cells. Circulation. 2004;109:1292-1298
26. Planat-Benard V, Silvestre J-S, Cousin B, André M, Nibbelink M, Tamarat R, Clergue M, Manneville C, Saillan-Barreau C, Duriez Plasticity of human adipose lineage cells toward endothelial cells physiological  and   therapeutic   perspectives.   Circulation. 2004;109:656-663
27. Kilroy GE, Foster SJ, Wu X, Ruiz J, Sherwood S, Heifetz A, Ludlow JW, Stricker DM, Potiny S, Green P, Halvorsen YD, Cheatham B, Storms RW, Gimble  Cytokine  profile  of human  adipose-derived stem cells: Expression of angiogenic, hematopoietic, and pro- inflammatory factors. J Cell Physiol. 2007;212:702-709
28. Ribeiro CA, Fraga JS, Grãos M, Neves NM, Reis RL, Gimble JM, Sousa N, Salgado The secretome of  stem  cells  isolated  from  the  adipose  tissue  and  wharton  jelly  acts differently  on central nervous  system  derived  cell populations.  Stem Cell  Res  Ther. 2012;3:18
29. Silva NA, Gimble JM, Sousa N, Reis RL, Salgado Combining adult stem cells and olfactory ensheathing cells:   The   secretome  effect.   Stem   cells   and   development. 2013;22:1232-1240
30. Cho YJ, Song  HS,  Bhang  S,  Lee S,  Kang  BG,  Lee  JC,  An  J,  Cha  CI,  Nam DH,  Kim. Therapeutic effects of human adipose stem cell‐conditioned medium on stroke. Journal of neuroscience research. 2012;90:1794-1802

31. Egashira Y, Sugitani S, Suzuki Y, Mishiro K,  Tsuruma  K,  Shimazawa  M,  Yoshimura  S, Iwama T, Hara The conditioned medium of murine and human adipose-derived stem cells exerts neuroprotective effects against experimental stroke model. Brain research. 2012;1461:87-95
32. Wei X, Du Z, Zhao L, Feng D, Wei G, He Y, Tan J, Lee WH, Hampel H, Dodel Ifats collection:The conditioned media of adipose stromal cells protect against hypoxia‐ischemia‐induced brain damage in neonatal rats. Stem Cells. 2009;27:478-488

33. Wei X, Zhao L, Zhong J, Gu H, Feng D, Johnstone B, March K, Farlow M, Du Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis. Neuroscience letters. 2009;462:76-79
34. Zhao L, Wei X, Ma Z, Feng D, Tu P, Johnstone B, March K, Du Adipose stromal cells- conditional  medium  protected   glutamate-induced   cgns   neuronal  death   by  bdnf. Neuroscience letters. 2009;452:238-240
35. Cousin B, André M, Arnaud E, Pénicaud L, Casteilla Reconstitution of lethally irradiated mice by cells isolated from adipose tissue. Biochemical and biophysical research communications. 2003;301:1016-1022
36. Han J, Koh YJ, Moon HR, Ryoo HG,  Cho  CH,  Kim  I,  Koh    Adipose  tissue  is  an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood.2009
37. Harms M, Seale Brown and beige fat: Development, function and therapeutic potential. Nature medicine. 2013;19:1252-1263
38. Rahman S, Lu Y, Czernik PJ, Rosen CJ, Enerback S, Lecka-Czernik Inducible brown adipose tissue, or beige fat, is anabolic for the skeleton. Endocrinology. 2013;154:2687-2701

39. Wu J, Cohen P, Spiegelman Adaptive thermogenesis in adipocytes: Is beige the new brown? Genes & development. 2013;27:234-250
40. Krings A, Rahman S, Huang S, Lu Y, Czernik P, Lecka-Czernik Bone  marrow  fat  has brown adipose tissue characteristics, which are attenuated with aging and diabetes. Bone. 2012;50:546-552
41. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500-1508
42. Peirce V, Carobbio S, Vidal-Puig The different shades of fat. Nature. 2014;510:76-83
43. Enerbäck S, Gimble Lipoprotein lipase gene expression: Physiological regulators at the transcriptional and post-transcriptional level. Biochimica et Biophysica Acta (BBA)- Lipids and Lipid Metabolism. 1993;1169:107-125
44. Rudolph MC, Neville MC, Anderson Lipid synthesis in  lactation: Diet  and  the fatty acid switch. Journal of mammary gland biology and neoplasia. 2007;12:269-281
45. Gimble JM, Katz AJ, Bunnell Adipose-derived stem cells for regenerative medicine. Circ Res. 2007;100:1249-1260

46. Bellows CF, Zhang Y, Chen J, Frazier ML, Kolonin Circulation of progenitor cells in obese  and lean   colorectal   cancer   patients.   Cancer   Epidemiology   Biomarkers   & Prevention. 2011;20:2461- 2468
47. Bellows CF, Zhang Y, Simmons PJ, Khalsa AS, Kolonin Influence of bmi on level of circulating progenitor cells. Obesity. 2011;19:1722-1726
48. Krijnen PA NB, Meinster E, Vo K, Musters RJ, Kamp O, Niessen HW,, Juffermans LJ. Acute myocardial infarction does not affect functional characteristics of adipose derived stem cells in rats, but reduces the number of stem cells in adipose tissue. IFATS Annual Meeting. 2014:100
49. Traktuev DO, Merfeld-Clauss S, Li J, Kolonin M, Arap W, Pasqualini R, Johnstone BH,March KL. A population of multipotent cd34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circulation research. 2008;102:77-85

50. Traktuev DO, Prater DN, Merfeld-Clauss S, Sanjeevaiah AR, Saadatzadeh MR, Murphy M, Johnstone BH, Ingram DA, March Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells. Circulation research. 2009;104:1410-1420
51. Merfeld-Clauss S, Gollahalli N, March KL, Traktuev Adipose tissue progenitor cells directly interact with endothelial cells to induce vascular network formation. Tissue Engineering Part A. 2010;16:2953-2966
52. Merfeld-Clauss S, Lupov IP, Lu H, Feng D, Compton-Craig P, March KL, Traktuev.  Adipose stromal cells differentiate along a smooth muscle lineage pathway upon endothelial cell contact via induction of activin a. Circulation research. 2014;115:800-809

53. Crisan M, Yap S, Casteilla L, Chen C-W, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang A perivascular origin for mesenchymal stem cells in multiple human organs. Cell stem cell. 2008;3:301-313
54. Ter Horst E, Naaijkens B, Krijnen P, Van Der Laan A, Piek J, Niessen Induction of a monocyte/macrophage phenotype switch by mesenchymal stem cells might contribute to improved infarct healing postacute myocardial infarction. Minerva cardioangiologica. 2013;61:617-625
55. Guisantes E,  Fontdevila  J,  Rodríguez    Autologous  fat   grafting   for   correction  of unaesthetic scars. Annals of plastic surgery. 2012;69:550-554
56. Klinger M, Caviggioli F, Klinger FM, Giannasi S, Bandi V, Banzatti B, Forcellini D, Maione L, Catania B, Vinci Autologous fat graft in scar treatment. Journal of Craniofacial Surgery. 2013;24:1610-1615
57. Klinger M, Marazzi M, Vigo D, Torre Fat injection for cases of severe burn outcomes: A new perspective of  scar  remodeling  and   reduction.   Aesthetic  plastic   surgery. 2008;32:465-469
58. Khouri RK, Smit JM, Cardoso E, Pallua N, Lantieri L, Mathijssen IM, Khouri Jr RK, Rigotti Percutaneous aponeurotomy and lipofilling: A regenerative alternative to flap reconstruction? Plastic and reconstructive surgery. 2013;132:1280-1290
59. Balkin DM, Samra S, Steinbacher Immediate fat grafting in primary cleft lip repair. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2014;67:1644-1650
60. Rigotti G,  Marchi  A,  Galie  M,  Baroni  G,  Benati  D,  Krampera  M,  Pasini  A, Sbarbati.  Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: A healing process  mediated by  adipose-derived  adult  stem  cells.  Plastic  and  reconstructive surgery. 2007;119:1409-1422

61. Villani F, Caviggioli F, Klinger F, Klinger Rehabilitation of irradiated head and neck tissues by autologous  fat   transplantation.   Plastic   and   reconstructive   surgery. 2009;124:2190-2191
62. Chang CC,  Thanik  VD,  Lerman  OZ,  Saadeh  PB,  Warren  SM,  Coleman  SR,  Hazen   Treatment   of   radiation   skin   damage   with   coleman   fat   grafting.   STEM   CELLS. 2007;25:3280-3281
63. Sultan SM, Stern CS, Allen Jr RJ, Thanik VD, Chang CC, Nguyen PD, Canizares O, Szpalski C, Saadeh PB, Warren Human fat grafting alleviates radiation skin damage in a murine model. Plastic and reconstructive surgery. 2011;128:363-372
64. Loder S, Peterson JR, Agarwal S, Eboda O, Brownley C, DeLaRosa  S,  Ranganathan  K, Cederna P, Wang SC, Levi Wound healing after thermal injury is improved by fat and adipose-derived stem cell isografts. Journal of Burn Care & Research. 2015;36:70-76

65. Sultan SM, Barr JS, Butala P, Davidson EH, Weinstein AL, Knobel D, Saadeh PB, Warren SM, Coleman SR, Hazen Fat grafting accelerates revascularisation and decreases fibrosis following thermal injury. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2012;65:219-227
66. Cuomo R, Zerini I, Botteri G, Barberi L, Nisi G, D’ANIELLO Postsurgical pain related to breast implant: Reduction with lipofilling procedure. In Vivo. 2014;28:993-996
67. Maione L,  Vinci  V,  Caviggioli  F,  Klinger  F,  Banzatti  B,  Catania  B,  Lisa  A,  Klinger   Autologous fat graft in postmastectomy pain syndrome following breast conservative surgery and radiotherapy. Aesthetic plastic surgery. 2014;38:528-532
68. Caviggioli F,  Maione  L,  Forcellini D,  Klinger  F,  Klinger    Autologous  fat   graft   in postmastectomy pain syndrome. Plastic and reconstructive surgery. 2011;128:349-352
69. Caviggioli F, Vinci V, Codolini Autologous fat grafting: An innovative solution for the treatment of post-mastectomy pain syndrome. Breast Cancer. 2013;20:281-282
70. Salgarello M, Visconti The role of sacrolumbar fat grafting in the treatment of spinal fusion instrumentation-related chronic  low  back  pain:  A  preliminary  report.  Spine. 2014;39:E360-E362
71. Faroni A, Terenghi G, Reid Adipose-derived stem cells and nerve regeneration: Promises and pitfalls. Int Rev Neurobiol. 2013;108:121-136
72. Vaienti L, Gazzola R, Villani F, Parodi Perineural fat grafting in the treatment of painful neuromas. Techniques in hand & upper extremity surgery. 2012;16:52-55
73. Marangi GF, Pallara T, Cagli B, Schena E, Giurazza F, Faiella E, Zobel BB, Persichetti Treatment of  early-stage  pressure  ulcers  by  using  autologous  adipose  tissue  grafts. Plastic Surgery International. 2014;2014
74. Lolli P, Malleo G, Rigotti Treatment of chronic anal fissures and associated stenosis by autologous adipose tissue transplant: A pilot study. Diseases of the Colon & Rectum. 2010;53:460-466
75. Cantarella G,  Baracca  G,  Forti  S,  Gaffuri  M,  Mazzola    Outcomes  of  structural  fat grafting for paralytic and non-paralytic dysphonia. Acta Otorhinolaryngologica Italica. 2011;31:154
76. DeFatta  RA,   DeFatta  RJ,   Sataloff      Laryngeal   lipotransfer:   Review   of   a   14-year experience. Journal of Voice. 2013;27:512-515
77. Sataloff    Autologous  fat   implantation  for  vocal  fold   scar.   Current  opinion  in otolaryngology & head and neck surgery. 2010;18:503-506

78. Cantarella G, Mazzola RF, Mantovani M, Baracca G, Pignataro Treatment of velopharyngeal insufficiency by pharyngeal and velar fat injections. Otolaryngology– Head and Neck Surgery. 2011;145:401-403
79. Papa N, Luca G, Sambataro D, Zaccara E, Maglione W, Gabrielli A, Fraticelli P, Moroncini G, Beretta L, Santaniello A. Regional implantation of autologous adipose tissue-derived cells induces a prompt healing of long-lasting indolent digital ulcers in patients with systemic sclerosis. Cell transplantation. 2014

80. Hovius SE, Kan HJ, Smit X, Selles RW, Cardoso E,  Khouri    Extensive  percutaneous aponeurotomy and lipografting: A new treatment for dupuytren disease. Plastic and reconstructive surgery. 2011;128:221-228
81. Verhoekx JS, Mudera V, Walbeehm ET, Hovius Adipose-derived stem cells inhibit the contractile myofibroblast in  dupuytren’s  disease.  Plastic  and  reconstructive  surgery. 2013;132:1139-1148

82. Bank J, Fuller SM, Henry GI, Zachary Fat grafting to the hand in patients with raynaud phenomenon: A  novel   therapeutic   modality.   Plastic   and   reconstructive   surgery. 2014;133:1109-1118
83. Damgaard OE, Siemssen Lipografted tenolysis. Journal of Plastic, Reconstructive & Aesthetic Surgery. 2010;63:e637-e638
84. Colonna M,   Scarcella   M,   d’Alcontres   F,   Delia   G,   Lupo      Should   fat   graft   be recommended in tendon scar treatment? Considerations on three cases (two feet and a severe burned hand). European review  for  medical  and  pharmacological  sciences. 2014;18:753-759
85. Merikanto JE, Alhopuro S, Ritsilä Free fat transplant prevents osseous reunion of skull defects: A new approach in the treatment of craniosynostosis. Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. 1987;21:183-188
86. Mojallal A,   Lequeux  C,  Shipkov  C,  Breton  P,  Foyatier  J-L,  Braye  F,  Damour   Improvement  of skin quality after  fat  grafting: Clinical observation and  an  animal  study. Plastic and reconstructive surgery. 2009;124:765-774
87. Lockwood  Superficial  fascial  system  (sfs)  of  the  trunk  and  extremities:  A  new concept. Plastic and reconstructive surgery. 1991;87:1009-1018

88. Song AY, Askari M, Azemi E, Alber S, Hurwitz DJ, Marra KG, Shestak KC, Debski R, Rubin Biomechanical properties of the superficial fascial system. Aesthetic Surgery Journal. 2006;26:395-403
89. Flynn     The   use   of   decellularized   adipose    tissue    to    provide    an    inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials. 2010;31:4715-4724
90. Brown BN, Freund JM, Han L, Rubin JP, Reing JE, Jeffries EM, Wolf MT, Tottey S, Barnes CA, Ratner Comparison of three methods for the derivation of a biologic scaffold composed of adipose tissue extracellular matrix. Tissue Engineering Part C: Methods. 2011;17:411-421
91. Wu I, Nahas Z, Kimmerling KA, Rosson GD, Elisseeff An injectable adipose matrix for soft tissue reconstruction. Plastic and reconstructive surgery. 2012;129:1247
92. Omidi E, Fuetterer L, Mousavi SR, Armstrong RC, Flynn LE, Samani Characterization and assessment of hyperelastic and elastic properties of decellularized human adipose tissues. Journal of biomechanics. 2014;47:3657-3663
93. Wang L,  Johnson  JA,  Zhang  Q,  Beahm  Combining  decellularized  human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering.  Acta biomaterialia. 2013;9:8921-8931
94. Healy C, Allen Sr The evolution of perforator flap breast reconstruction: Twenty years after the first diep flap. Journal of reconstructive microsurgery. 2014;30:121-125
95. LoTempio MM, Allen Breast reconstruction with sgap and igap flaps. Plastic and reconstructive surgery. 2010;126:393-401
96. Erić M,  Mihić N,  Krivokuća Breast  reconstruction  following  mastectomy; patient’s satisfaction. Acta Chir Belg. 2009;109:159-166
97. Diaz-Flores L, Gutierrez R, Lizartza K, et Behavior of In Situ Human Native Adipose Tissue CD34+ Stromal/Progenitor Cells During Different Stages of Repair. Tissue-Resident CD34+ Stromal Cells as a Source of Myofibroblasts. Anatomical record. 2014.
98. Gil-Ortega M, Garidou L, Barreau C, et Native adipose stromal cells egress from adipose tissue in vivo: evidence during lymph node activation. Stem cells. 2013;31(7):1309-20.

SATURDAY, 01 OCTOBER 2016 / PUBLISHED IN BLOG

Researchers from the Medical University of South Carolina (MUSC) and the University of Pennsylvania have discovered a new methodology for purifying liver cells generated from induced pluripotent stem cells (iPSCs) that could facilitate progress toward an important clinical goal: treating patients with disease-causing liver mutations by transplanting unmutated liver cells derived from their own stem cells.

Background on Liver Cell Generation from iPSCs

Previous attempts to generate liver-like cells from stem cells have yielded heterogeneous cell populations with little similarity to diseased livers in patients.

The Role of the Next Generation Genetic Association Studies Program

The National Heart, Lung, and Blood Institute (NHLBI)’s Next Generation Genetic Association Studies Program (Next Gen) was created to bank stem cell lines sourced from patients in genome-wide association studies (GWAS). The goal of the Next Gen Lipid Conditions sub-section, a collaborative effort between Stephen A. Duncan, Ph.D., chair of regenerative medicine at MUSC, and Daniel J. Rader, M.D., and Edward E. Morrisey, Ph.D., both at the University of Pennsylvania, is to help determine the genetic sources of heart, lung, or blood conditions that also include the liver.

Genome-Wide Association Studies (GWAS)

GWAS studies map the genomes in hundreds of people to look for genetic mutation patterns that differ from the genomes of healthy individuals. As GWAS studies map more genomes, they become more likely to find the correct genetic mutations that cause a disease. Once a panel of suspected mutations is built, stem cells from these individuals can be manipulated in culture dishes to differentiate into any of the body’s cells. The cells can be screened to learn more about the mutations and to test panels of drugs that might ultimately help treat patients harboring a disease.

Challenges in Cell Manipulation Process

Problems arise during the cell manipulation process. For example, iPSCs persistently refuse to mature uniformly into liver-like cells when fed growth factors. Traditionally, antibodies have been used to recognize features of maturity on the surfaces of cells and purify cells that are similar, an approach that has been crucial to stem cell research. But available antibodies that recognize mature liver cells are scanty and tend to recognize many different kinds of cells. The many types of cells in mixed populations have diverse characteristics that can obscure underlying disease-causing genetic variations, which tend to be subtle.

Introduction of Chemo Proteomic Cell Surface Capture (CSC) Technology

Instead of relying on antibodies, Duncan and his team embraced a new technology called chemo proteomic cell surface capture (CSC) technology. CSC technology allowed the researchers to map the most highly produced proteins on the surface of liver cells during the final stages of differentiation of stem cells into liver cells. The most abundant protein was targeted with an antibody labeled with a fluorescent marker and used to sort the mature liver cells from the rest.

Successful Generation of Pure Liver-like Cells

The procedure was highly successful: The team had a population of highly pure, homogeneous, and mature liver-like cells. Labeled cells had far more similar traits of mature hepatocytes than unlabeled cells. Pluripotent stem cells that had not differentiated were excluded from the group of labeled cells.

“That’s important,” says Duncan. “If you’re wanting to transplant cells into somebody that has liver disease, you really don’t want to be transplanting pluripotent cells because pluripotent cells form tumors called teratocarcinomas.”

Future Implications

Duncan cautioned that transplantation of iPSC-derived liver cells is not yet ready for translation to the clinic, but the technology for sorting homogeneous liver cells can be used now to successfully and accurately model and study disease in the cell culture dish.

“We think that the ability to generate pure populations will get rid of the variability, and therefore really help us combine with GWAS studies to identify allelic variations that are causative of a disease, at least in the liver,” he says.

Contributions to the Study

Researchers at the University of Minnesota (Minneapolis) and the Medical College of Wisconsin (Milwaukee) contributed to the study, published August 25, in Stem Cell Reports.