James Sherley, Asymmetrex, considers the potential benefits to stem cell medicine and stem cell science
Presently, in stem cell science and stem cell medicine, there exists a high degree of prejudice against private medical practices that offer stem cell treatments. When describing these private stem cell clinics, many reports written by disapproving stem cell scientists and stem cell medicine clinicians refer to the treating physicians as charlatans exploiting patients’ desperation and ignorance for money. Additionally, they’re regarded as unknowing pawns, themselves exploited by unsavory purveyors of poorly defined purported stem cell preparations. These reports warn that the supplied preparations may not only be ineffective, but they also may not contain any stem cells at all.
In contrast to this pejorative view held by well-known scientists and physicians in the field of stem cell biomedicine, many patients and patient advocate groups actively demand freedom for private stem cell clinics to operate without interference. The general sentiment being that regulatory agencies, like the US Food and Drug Administration (FDA) might restrict private clinics from exploring potentially beneficial novel stem cell treatments.
One factor responsible for this opposing view by patients is impatience with the generally slow, often protracted, and highly expensive regulatory path that new medical treatments must travel before receiving approval for general use. But there is also a fundamental distinction at play that could be seen as giving considerable credence to patients’ call for unregulated operation of private stem cell clinics. That distinction is the difference in the core principles that motivate stem cell medicine versus those that motivate stem cell science. Whereas stem cell medicine is successful when a treatment is followed by an improvement in the health and well-being of individual patients, stem cell science has the goal of assembling a body of scientific evidence that reliably predicts that a treatment will provide a measurable reduction of illness for a significant fraction of similarly affected patients.
The history of medicine is filled with important medical advances that began with the observations of individual physicians while treating small groups of patients, or even a single patient. Though it can be argued that such initial medical discoveries and insights were later substantiated with larger numbers of patients across more medical practices and hospitals, the rich history of routine medical care should not be overlooked in the present controversy. So, in the absence of significant treatment-related safety issues, physicians, acting diligently to relieve the pain and suffering of their patients by stem cell-based treatments, are in fact an important component of stem cell medical research.
The basic concept of the clinical trial, comparing the outcomes for groups of patients receiving different treatments, has existed for as long as the concept of medicine itself, which has existed for millennia. However, the regulation of medical treatments in the US by the FDA began only a little more than a century ago; and the agency’s current degree of authority has been in place only since 1988. FDA regulators have the charge of ensuring that new medical treatments are developed and approved through science-based clinical trials. What’s more, these studies are trials that have the goal of yielding safe and effective treatments that will be either widely effective or effective for well-defined patient populations. Similarly charged regulatory agencies exist in many other countries worldwide.
The polemics against private stem cell clinics rarely acknowledge that many physicians who have introduced stem cell treatments into their private practices do so with the goal of providing the newest advances in medicine to their patients. Their intentions are good and ethical, and they seek to provide safe therapies that may alleviate pain and ailments that resist other available therapies. Today, unfortunately, many of these innovative physicians are still unwarrantedly stereotyped by the past highly derogatory image of “stem cell tourism.”
In the US, the term “stem cell tourism” came into usage in 2009 to describe private stem cell clinics, located “off shore” in nearby locales like some Caribbean island countries, that were in fact owned and controlled by concerns in the US. These clinics were established to evade FDA regulations that prohibited treatment with stem cell preparations; and some are reported to have extracted exorbitant fees from desperate patients for ineffective and possibly dangerous treatments.
Stem cell medicine is now in a new day with a rapidly growing number of private stem cell clinics that warrant more productive responses than only alarmist polemics. A 2009 report surveying the number of private stem cell clinics in the US with public websites listed only 19. A similar report this year, only seven years later, identified more than 400. This explosion in number was very likely fueled by the recent 2014 issuance of an FDA guidance that permits treatments that use “minimally manipulated” human cells and tissues. Many interpret this definition to include uncultured autologous stem cell-containing tissue fractions from bone marrow and fat, which are readily accessible by approved medical procedures developed for bone marrow transplantation therapies and medical cosmetics. Also included are readily harvested allogeneic stem cell sources like cord blood, amniotic fluid, and amniotic and placental cell membranes.
Continuing to ignore or prohibiting this remarkable development in medical care could result in a regrettable loss of a powerful means to accelerate progress in stem cell medicine. Instead, all the key stakeholders – patients and patient advocates, physicians, suppliers, and regulators – should work together to promote at least two improvements in private stem cell clinical practice. These two improvements are systems for quality assurance and treatment outcome dissemination. First, quality control standards should be established for stem cell treatment preparations. At a minimum, these standards should include determinations of: 1) the total nucleated cell count; 2) the viable nucleated cell count; and 3) the positive cell fraction for at least one stem cell-associated biomarker.
Standards 1 and 2 could be readily determined at the point of care by medical personnel in private clinics. Standard 3 might require that a small portion of treatment preparations are preserved and sent to commercial laboratories that perform biomarker detection assays. Treatments would not be required to wait for the completion of these analyses. Analysis results would be used retrospectively to monitor the quality and properties of treatment preparations and prospectively to design future treatments.
A pervasive quality control limitation, for both unregulated private clinics and approved clinical trials, is the lack of biomarkers with sufficient specificity to count tissue stem cells for treatment dose determinations. However, based on predictions from historical stem cell fraction data, results with biomarkers that identify both stem cells and committed progenitors cells could provide a degree of confidence that stem cells were actually present in treatment samples. Industry suppliers of allogeneic stem cell treatment preparations must be required to supply similar quality certifications for each of their supplied lots of stem cells.
Patients must be educated to demand these three minimal quality certifications. This new patient demand should incentivize private clinic physicians to guarantee the certifications for autologous treatment samples that they harvest themselves, and also to require them from their suppliers of allogeneic stem cell treatment preparations. When physicians refuse to purchase uncertified stem cell preparations because their patients demand certification, suppliers will be incentivized to certify their production process accordingly. A treatment supply system incentivized in this manner by informed patients could eventually operate entirely on an unenforced basis. However, an important regulatory role for agencies like the FDA would be to act as independent certification-auditing agents.
Once the quality of stem cell treatment samples is assured, a door opens for the second improvement, which is implementing both standardized and ad hoc methods for private clinics to document and report their treatment outcomes with respect to the three quality standards and clinical features of their patients. Such elemental case reports may be organized and reported in the medical literature by individual clinics, by local clinic consortia, or by national and international efforts organized and supported by government, corporate, or private agencies. The well-worn complex incentives of biomedical research enterprises can be expected to drive this important activity.
When adopted, the two recommended improvements would immediately improve the quality of medical care delivered to stem cell treatment patients. They would also allow the large and growing volume of stem cell medicine now practiced in private clinics to contribute more effectively to advancing both stem cell science and stem cell medicine.
*James L. Sherley, M.D., Ph.D., is the Founder & Director of Asymmetrex, a company providing the first-ever adult tissue stem cell counting technology