Mesenchymal stem cells (MSCs) were initially discovered in bone marrow by Friedenstein in 1976.¹ Stem cells are commonly found in bone marrow and can also be found in adipose tissue, cord blood, peripheral blood, fallopian tubes, fetal liver tissue and lung tissues.² Adult mesenchymal stem cells have multi-lineage differentiation and can transform into osteoblasts, adipocytes, chondrocytes, myocytes, and marrow stromal cells.³ MSCs harvested from bone marrow and condensed into bone marrow aspirate concentrate (BMAC) have been shown to significantly improve outcomes for patients with knee⁴ and hip osteoarthritis.⁵ Level III evidence is also available to support the use of MSCs to treat multiple sclerosis and critical limb ischemia.

While most scientific research examines the use of BMAC to treat osteochondral conditions, the stem cell industry is complicated by two major factors; sham “amniotic stem cell” products and illegal fat stem cell clinics. A simple web search for ‘stem cell clinics’ will populate your browser with providers touting the healing power of stem cells without scientific evidence. The FDA is cracking down on clinics offering amniotic stem cell injections or fat stem cell treatments for pain, arthritis and soft tissue conditions. These untested procedures put patients lives and medical licenses at risk. This post covers the fundamental differences between scientifically supported BMAC procedures, sham amniotic tissue products, and illegal fat stem cell clinics.

FDA Approved Living Tissue Products

Currently the FDA classifies all living tissue products as 351 drugs. As such, the FDA requires rigorous clinical trials to demonstrate the product’s safety and efficacy for one specific application. Taking a drug to trial is multi-year multi-million dollar process designed to keep the public safe. If the drug is proven to be safe and effective, then 351 classification is awarded.

As of May 8, 2018 there are only 7 FDA approved cord blood products on the market:

Allocord from the Cardinal Glennon Children’s Medical Center

Clevecord from the Cleveland Cord Blood Center

Hemacord from the New York Blood Center Inc.

Ducord from the Duke University School of Medicine

HPC Cord Blood from Clinimmune Labs at the University of Colorado Cord Blood Bank

HPC Cord Blood from LifeSouth Community Blood Centers, Inc.

HPC Cord Blood from Bloodworks

The preceding products are approved by the FDA to treat “patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.”⁶

Living cord blood is utilized to treat hematopoietic conditions such as leukemia and lymphoma. Federally regulated cord blood falls under the umbrella of allogeneic stem cell procedures. Allogenic stem cells, such as amniotic stem cells, cord blood, wharton’s jelly or placenta stem cells, originate from another person. Because these products are allogeneic they come with increased risk of adverse events and allergic reaction. For these treatments to be effective, the donor must be a match and the stem cells must be living.

Sham Amniotic Tissue Products

With the exception of the aforementioned 7 cord blood companies there are many products on the market illegally claiming to contain live stem cells. Some companies have successfully passed off chopped up amniotic tissue as a living stem cell product. The amniotic membrane is acquired after a live birth, powdered and then freeze dried. The process kills all living tissue, but spares a small amount of growth factors. Some physicians are offering to inject the dead amniotic tissue into patients as a ‘stem cell therapy’. Purchasing such products is not only illegal according to the FDA, it puts patients and medical licensing at risk.

Companies selling amniotic tissue products file a simple online form to register their products as 361 tissues. According to the FDA 361 tissues must be non-viable, or dead. Companies marketing amniotic stem cells products often claim their products contain live stem cells, which is an unlawful misrepresentation of their product or an unregulated 351 cell drug. Purchasing fraudulent products and offering untested stem cell procedures has resulted in the revocation of medical licensing in Florida, California, and Oregon.

Illegal Fat Stem Cell Clinics

In addition to the fraudulent cord blood products, in 2012 the FDA spoke out against fat stem cell clinics recklessly administering stromal vascular fraction procedures. US Stem Cell in Florida and Cell Surgical Network in Southern California offered experimental fat stem cells treatments claiming to cure cancer, heart disease,⁷ multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). The practitioners did not have scientific evidence to support their claims. In a process called stromal vascular fraction (SVF) the clinics harvested adipose tissue, treated the sample with an enzyme that partially digests the structure of fat then further processed the sample to extract a fraction of a stromal cell. The heavily processed lipoaspirate cells are subsequently injected into various tissues with sometimes detrimental effects.

FDA considers stem cells extracted from fat to be a cell drug and as such require rigorous clinical testing to establish safety and efficacy for a specific condition (351 drug approval). There is not evidence to support SVF to treat cancer, heart disease, MS or ALS, and injecting fat stem cells can lead to lasting adverse effects.

March of 2017, the Washington Post reported the blinding of three south Florida women from unregulated stem cell procedures. Though the study was listed on ClinicalTrials.gov, the scientific community has yet to research the effects of processed fat stem cells injected into the eye to treat macular degeneration. In order to assure the safety of patients, researchers must first produce positive results in animal models before experimental treatments are applied in human models.

SVF for Fat Augmentation Procedures

There is scant evidence available to support adipose stem cells for musculoskeletal conditions. For example there were over 1100 BMAC articles published in 2013 compared to just 17 articles published regarding SVF. The US Food and Drug Administration classifies stem cells derived from fat as cellular drugs because the material is more than minimally processed and often applied in non-homologous tissues. This classification system prevents doctors from extracting and processing adipose tissue until controlled clinical trials are completed, and in 2017 the FDA began cracking down on unapproved SVF clinics across the US.

Though the procedures are only available abroad, promising research does exists to support SVF in fat augmentation procedures. Fat stem cells are capable of differentiating into multiple mesodermal tissue and secrete vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor-β in the presence of damaged tissue.⁸

Clinical evidence is available to support SVF to improve outcome for patients receiving soft tissue augmentation. Researchers in Tokyo performed a study on stromal vascular fraction in breast fat augmentation procedures in 2007. Researchers mixed SVF cells with adipose tissue collected from thighs, abdomen or lower leg. On average 270 ml of the mixture was injected into the breast with 100-200 ml of tissue retention at 24 months. Adverse effects such as cyst formation, microcalcification and rigid tissue was detected in 10% of the 40 participants.⁹ Stem cells derived from adipose tissue increased the viability of fat transplants, but still there is no clinical evidence to support claims that SVF will have a positive impact on cancer, heart disease, musculoskeletal conditions, MS or ALS.

FDA Approved Stem Cell Procedures

Unregulated SVF procedures are completely distinct from BMAC procedures. Practitioners extract bone marrow from the iliac crest of a patient. The bone marrow aspirate contain 0.01-0.02% MSCs.¹⁰ Clinicians concentrate aspirated bone marrow with commercially available kits. Stanford University doctors found the EmCyte PureBMC BMAC system significantly increased progenitor colonies and enriched functional mesenchymal stem cell subpopulations while maintaining 90% cell viability.

MSCs harvested from bone marrow and concentrated into BMAC don’t undergo the heavy extraction process of SVF. BMAC stem cells maintain their original structure and can be safely injected into damaged chondral tissues. There is clinical evidence to support the safety and efficacy of bone marrow stem cells to treat knee and hip osteoarthritis.

The Future of Stem Cell Therapy

It is vital for practitioners and patients alike to understand the fundamental differences between scientifically supported BMAC procedures, sham amniotic tissue products, and illegal fat stem cell clinics. BMAC procedures have always been considered safe according to the FDA, while sham amniotic tissue products and recklessly injected adipose stem cells put patients in danger and doctors in legal trouble. Doctors who purchase sham amniotic stem cell products or participate in illegal fat stem cell clinics endanger patients while defaming reputable stem cell procedures such as BMAC.

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References

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