Unless you have been in hibernation, you know the promise of stem cells, their origin, and the hopes that stem cell therapies hold for the abating, or even outright curing, of a dizzying array of conditions. The 3 main sources for human stem cells are embryonic, umbilical cord, and adult stem cells. The mere mention of stem cells, especially of embryonic origin, evokes other multipotentialities rooted in emotion, politics, ethics, regulations, and purveyors.
The aforementioned aside, wound care practitioners want to know about the potential of stem cell therapy for their patients and for their competencies as a professional. Essentially, a stem cell is undifferentiated and has the potential to differentiate into a specialized function, such as mesenchyme, and, ultimately, connective tissue-the tissue of interest for wound care practitioners.
This month's continuing education activity discusses the potential of stem cell therapy for use in wound care and provides a review of the literature and some constructs for potential delivery systems for topical therapy to chronic wounds. As wound care practitioners, we first need to know the origin of the stem cells for a given patient, which raises several questions. If the stem cells are autologous, does the patient have to undergo a painful bone biopsy? And if so, what are the bedside ramifications? If the stem cells come from other sources, have they been examined by the common standards and practices for therapeutics, such as clinical trials, the Food and Drug Administration (FDA), and institutional review boards? Finally, if the practices are investigational, have they gone through the various phases of research protocols?
Research usually begins with animal and laboratory studies, which usually last about 4 to 5 years. Proof of concept is a major goal of phase I trials. Given that these are in vivo (animal models) and in vitro research protocols, strength-of-evidence ratings are low, and although the investigators may demonstrate statistical significance, clinical significance is the goal.
Phase I clinical trials are used for safety and efficacy and usually involve small numbers (approximately 30) of patients. The dosage and delivery systems are also tested during this phase. In the case of stem cells, the vehicle for delivery, gel, dressing, or other modalities is tested as well.
Phase II clinical trials are used to expand the work done in the previous phase but with more patients, usually about 100, for statistical and clinical significance. At this point, an investigational drug could be used for research. The main objective during this phase is to see if the stem cell therapy actually works. Strength-of-evidence ratings are better in this phase, and these trials may involve multiple organizations under the direction of a principle investigator.
Phase III clinical trials are used to conduct randomization single- and double-blind placebo trials and to compare stem cells to another therapy, for example. It is these studies that give the highest strength-of-evidence ratings. And, it is during this stage that the FDA will potentially grant approval for further use.
Phase IV trials usually involve postmarketing studies to delineate additional information, including the drug's risks, benefits, and optimal use in the clinical environment.
It is important to remember that, in all of the phases of clinical trials, which can take years and millions of dollars to complete, patient safety is the sine qua non of patient-oriented clinical research and patient care. Although the review by Brower et al on stem cell therapy is educational and looks to the advances in wound care, we must always consider the clinical research issues, strength-of-evidence ratings, cost, efficacy, and clinical outcomes. As progressive clinicians, we must embrace the future, but maintain our core values.
Richard "Sal" Salcido, MD
National Institutes of Health. Understanding clinical trials. http://clinicaltrials.gov/ct2/info/understand
. Last accessed September 26, 2011.