Commentary

Stem cell therapy presents strong hype, weak science

Anthony A. Romeo, MD
Anthony A. Romeo

Stem cell therapy has rapidly become a publicly recognized treatment for all types of musculoskeletal conditions, including tendinopathies, tendon tears, bone healing or fusion and arthritis. Many practicing orthopedic surgeons and allied health care providers offer stem cell treatment for the management of chronic conditions, such as tendinopathy and arthritis, as well as an adjunct during surgical procedures, such as rotator cuff repairs, other tendon repairs, spine surgery and fracture nonunion.

However, the science related to the effectiveness of stem cell treatment in humans has lacked strong evidence and currently should be considered in its infancy. While there are scattered publications with statistically significant results using higher levels of evidence methods, these are frequently underpowered studies to show results beyond chance. Furthermore, some studies include curious findings, such as failed tendon healing in the non-treatment group that is dramatically different from previously published literature, while the healing rate in the stem cell treatment group matches the results of previous literature.

Science demands reproducibility, and to date, most studies are not reproducible when the stem cell treatment cohort is highly advantageous. This was similarly demonstrated in the platelet-rich plasma (PRP) literature during the past decade, and has helped fuel the idea that growth factors and proteins alone are not enough to change outcomes, but adding stem cells may be the key ingredient to unleash the full biologic potential of healing.

Regenerate normal issue

The concept of “regenerative medicine” was initially discussed in the early 1990s. Leland R. Kaiser, PhD, defined regenerative medicine as “a new branch of medicine that attempts to change the course of chronic disease and in many instances, regenerate tired and failing organ systems.” Today, we have yet to develop methods of regenerating normal tissue such as cartilage and tendons. Many patients do not realize there is no technique today to regenerate normal hyaline cartilage to resurface an arthritic joint and there is no reliable technique to regenerate the normal sharpey fiber connection between tendon and bone after the development of tendinopathy or tendon tear. In 2017, regenerative medicine is sold as a product when it is still a vision. Much of this would not be too disturbing if it were not for the high prices charged for these services.

Ethically, stem cell treatments have been demonstrated to be safe. Stem cells from the patient are harvested, then delivered to the affected site. However, the other components of ethical behavior as described by Niemansburg and colleagues are skeptical at best. Rarely are risks discussed with patients, other than the possibility the treatment may not be effective. There is no discussion of possible long-term risks, which are unknown at this time. Selection of participants is primarily based on financial resources, not evidence-based studies, as the treatments are not approved by the FDA and are not covered by insurance. Patient expectations are high, but rarely are they informed that regeneration of normal tissue is unlikely and the primary effect of treatment is pain relief or palliation of symptoms.

In September 2016, the FDA held a hearing on the regulation of human cells, tissues and cellular and tissue-based products. The purpose of the meeting was to discuss the need and method to regulate treatments involving human cells and tissues. The FDA defines this area as HCT/Ps, which are articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion or transfer into human recipients.

The FDA first announced a proposed approach to the regulation of HCT/Ps in 1997, but the regulatory framework became effective 8 years later. The key factors in the regulation included the use of the HCT/Ps in the same surgical procedure and minimal manipulation of human cells, tissues, and cellular and tissue-based products. At that time, the regulatory guidelines did not restrict or penalize the marketing of this therapy, which frequently included unproven information about the capacity of stem cell treatment to regenerate normal tissues or to treat or cure diseases. Arguments against FDA involvement include that it lacks the authority to regulate the treatments because stem cell treatment and regenerative medicine behavior fall under the category of practicing medicine, which the FDA does not regulate.

Small step ahead

The use of PRP, stem cells and other blood and human tissue products is a small step in the goal of regenerating diseased, degenerated or injured tissues. The science of tissue engineering, combining pluripotential cells, growth factors, synthetic or human tissue scaffolds, and stable mechanical and electrical environments, will ultimately define the ability to regenerate parts of the normal human body.

The environment related to stem cells is rich with false claims of curing chronic diseases, avoiding or preventing proven medical and surgical treatments without reasonable scientific evidence and high fees. While the current political climate in Washington is focused on reducing government involvement at the federal level, this industry appears to be on a collision course with greater government involvement, oversite, enforcement and penalties through the FDA.

Disclosure: Romeo reports he receives royalties, is on the speaker’s bureau and a consultant for Arthrex; does contracted research for Arthrex and DJO Surgical; receives institutional grants from AANA and MLB; and receives institutional research support from Arthrex, Ossur, Smith & Nephew, ConMed Linvatec, Athletico and Miomed.

Anthony A. Romeo, MD
Anthony A. Romeo

Stem cell therapy has rapidly become a publicly recognized treatment for all types of musculoskeletal conditions, including tendinopathies, tendon tears, bone healing or fusion and arthritis. Many practicing orthopedic surgeons and allied health care providers offer stem cell treatment for the management of chronic conditions, such as tendinopathy and arthritis, as well as an adjunct during surgical procedures, such as rotator cuff repairs, other tendon repairs, spine surgery and fracture nonunion.

However, the science related to the effectiveness of stem cell treatment in humans has lacked strong evidence and currently should be considered in its infancy. While there are scattered publications with statistically significant results using higher levels of evidence methods, these are frequently underpowered studies to show results beyond chance. Furthermore, some studies include curious findings, such as failed tendon healing in the non-treatment group that is dramatically different from previously published literature, while the healing rate in the stem cell treatment group matches the results of previous literature.

Science demands reproducibility, and to date, most studies are not reproducible when the stem cell treatment cohort is highly advantageous. This was similarly demonstrated in the platelet-rich plasma (PRP) literature during the past decade, and has helped fuel the idea that growth factors and proteins alone are not enough to change outcomes, but adding stem cells may be the key ingredient to unleash the full biologic potential of healing.

Regenerate normal issue

The concept of “regenerative medicine” was initially discussed in the early 1990s. Leland R. Kaiser, PhD, defined regenerative medicine as “a new branch of medicine that attempts to change the course of chronic disease and in many instances, regenerate tired and failing organ systems.” Today, we have yet to develop methods of regenerating normal tissue such as cartilage and tendons. Many patients do not realize there is no technique today to regenerate normal hyaline cartilage to resurface an arthritic joint and there is no reliable technique to regenerate the normal sharpey fiber connection between tendon and bone after the development of tendinopathy or tendon tear. In 2017, regenerative medicine is sold as a product when it is still a vision. Much of this would not be too disturbing if it were not for the high prices charged for these services.

Ethically, stem cell treatments have been demonstrated to be safe. Stem cells from the patient are harvested, then delivered to the affected site. However, the other components of ethical behavior as described by Niemansburg and colleagues are skeptical at best. Rarely are risks discussed with patients, other than the possibility the treatment may not be effective. There is no discussion of possible long-term risks, which are unknown at this time. Selection of participants is primarily based on financial resources, not evidence-based studies, as the treatments are not approved by the FDA and are not covered by insurance. Patient expectations are high, but rarely are they informed that regeneration of normal tissue is unlikely and the primary effect of treatment is pain relief or palliation of symptoms.

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In September 2016, the FDA held a hearing on the regulation of human cells, tissues and cellular and tissue-based products. The purpose of the meeting was to discuss the need and method to regulate treatments involving human cells and tissues. The FDA defines this area as HCT/Ps, which are articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion or transfer into human recipients.

The FDA first announced a proposed approach to the regulation of HCT/Ps in 1997, but the regulatory framework became effective 8 years later. The key factors in the regulation included the use of the HCT/Ps in the same surgical procedure and minimal manipulation of human cells, tissues, and cellular and tissue-based products. At that time, the regulatory guidelines did not restrict or penalize the marketing of this therapy, which frequently included unproven information about the capacity of stem cell treatment to regenerate normal tissues or to treat or cure diseases. Arguments against FDA involvement include that it lacks the authority to regulate the treatments because stem cell treatment and regenerative medicine behavior fall under the category of practicing medicine, which the FDA does not regulate.

Small step ahead

The use of PRP, stem cells and other blood and human tissue products is a small step in the goal of regenerating diseased, degenerated or injured tissues. The science of tissue engineering, combining pluripotential cells, growth factors, synthetic or human tissue scaffolds, and stable mechanical and electrical environments, will ultimately define the ability to regenerate parts of the normal human body.

The environment related to stem cells is rich with false claims of curing chronic diseases, avoiding or preventing proven medical and surgical treatments without reasonable scientific evidence and high fees. While the current political climate in Washington is focused on reducing government involvement at the federal level, this industry appears to be on a collision course with greater government involvement, oversite, enforcement and penalties through the FDA.

Disclosure: Romeo reports he receives royalties, is on the speaker’s bureau and a consultant for Arthrex; does contracted research for Arthrex and DJO Surgical; receives institutional grants from AANA and MLB; and receives institutional research support from Arthrex, Ossur, Smith & Nephew, ConMed Linvatec, Athletico and Miomed.