Tuesday, November 5, 2024
Subscribe American Journal of Medicine Free Newsletter
CommentaryAlpert's EditorialsStem Cell Therapy: The Phoenix in Clinical Medicine?

Stem Cell Therapy: The Phoenix in Clinical Medicine?

Dr. Joseph S. Alpert

The Phoenix is a mythical bird with brightly colored plumage known in ancient Greek for the legend of its rebirth. After a long life, the Phoenix dies in a fire of its own making and then rises again reborn from the ashes. This myth parallels current feverish beliefs concerning the ability of stem cell therapy to regenerate tissues in diseased organs. Investigation into stem cell therapy has become one of the most intriguing areas of basic science and clinical research during the last decade. The concept of stem cell-based tissue regeneration has raised ample hopes in the eyes of health care practitioners and patients seeking repair of injuries to a variety of organs damaged by serious illnesses, which in the recent past were considered “incurable” or “irreversible.” The hope has been that such regenerative therapy would reduce associated morbidity and mortality rates. The news media and the general public have already taken an enthusiastic attitude towards this new and exciting concept of clinical therapeutics. In 2010, the US Department of Health and Human Services published an optimistic report entitled “2020: A New Vision—A Future for Regenerative Medicine.”1 However, despite this enthusiasm, a number of clinical studies have reported inconsistent findings at this point, warning of a long road before these therapies can become part of daily clinical practice.23456

Recently, the New England Journal of Medicine published 2 articles involving stem cell therapy for 5 patients with macular degeneration. In both reports, the injected stem cells were derived by laboratory manipulation from the patient’s own cells, that is, autologous.78 In the first report, Mandai et al7 reported that a sheet of stem cells derived from the patient’s skin fibroblasts were surgically placed under the retina with resultant engraftment. They noted that although the sheet of cells remained intact and viable 1 year later, there was no improvement in vision, and instead, macular edema had developed. In the second report, Kuriyan et al8 examined 3 patients who had been treated at a self-proclaimed “stem cell clinic” in the community. Each had received intraocular injections of alleged stem cells derived from the patient’s own adipose tissue. These patients suffered loss of vision associated with intraocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, and retinal detachment or lens displacement. In an accompanying editorial, George Q. Daley from Children’s Hospital and Harvard Medical School referred to the treatment received by the 3 patients whose vision deteriorated as “careless” and a “wanton misapplication of cellular therapy.”3

A number of clinical studies have employed stem cell modalities in patients with ischemic heart disease and reduced left ventricular function.456 The commonest population studied involved individuals with acute, subacute, or chronic myocardial infarction (>30 days post infarction). Adult stem cells in the form of cardiac progenitor cells, mesenchymal stem cells, adipose-derived stem cells, and bone marrow-derived stem cells are being used in 14 ongoing clinical trials.6 A simplistic view of the hypothesis for these trials is that the administered pluripotent cells would grow and differentiate into functioning myocytes when implanted into the myocardium, thereby replacing dying cardiomyocytes and improving overall ventricular function. Endothelial progenitor cells have also been tested in a smaller number of trials, under the assumption that this biological therapy would lead to neovascularization with subsequent improvement in myocardial perfusion and function. At this point in time, over 2000 patients with ischemic heart disease have been entered into clinical trials employing one form or another of stem cell therapy.5 Perhaps due to the biological nature of these infusions, and thus, the inherent variation in the constituent products, the results of these clinical trials have been in conflict with each other. Among 20 published trials of ischemic heart disease, 13 trials showed no significant improvement in left ventricular function.5 Even in trials where benefit has been demonstrated, the improvement has been quite modest.

A small number of adverse events have been observed in early trials of cell therapy. Theoretically, possible side effects that might result from stem cell injection include failure of retaining stem cells in the desired location, tumorigenesis, and adverse immunological responses if an allogeneic source of stem cells is used. To date, very few of these potential problems have been reported in the clinical trials performed, leading to the impression that this biologic therapy is safe, although not completely proven as yet to result in marked long-term amelioration of cardiac function. One meta-analysis did show that injection of bone marrow cells into the myocardium seemed apparently safe, with minimal adverse effects.9

The mixed results obtained so far involving stem cell therapy support the importance of an interplay between basic science investigators and clinical researchers to maximize the likelihood of success for future testing of one or more of the various cellular therapeutic modalities. Considerably more basic science and clinical investigation will be required before this new modality can be recommended for patients with a variety of illnesses. Future work in this area will require standardization of the protocols, with rigorous attention paid to patient medical condition, timing of administration, quantity of the biologic material infused, the various stem cell sources employed, and the technique(s) of cell delivery or infusion, including not only the cells but also any necessary matrix or growth factors that will enable the cells to engraft in the right place and synchronize with the host cells.10 One interesting discovery is that cardiosphere cells secrete vesicles containing a bundle of biological active factors, that is, exosomes, which have healing power, providing the potential for bypassing cell injection.11 Although 4 clinical trials have entered Phase III, from a clinical point of view, large scale, double-blind randomized studies with standardized cell preparations, and matured techniques of delivery will be needed to effectively evaluate the potential clinical benefit of this new therapy.

With respect to the large and growing population of so-called “stem cell clinics” that offer patients with serious diseases–for example, macular degeneration, spinal cord injury, amyotrophic lateral sclerosis, and multiple sclerosis–“proven success” at considerable personal cost, Daley stated it well in his recent editorial: “The International Society for Stem Cell Research has recently released guidelines for clinical translation of stem cells.12 The guidelines highlight the stark distinction between innovative treatments … proven in rigorous clinical trials … and the unproven interventions that are offered by practitioners who are naïve regarding the biologic complexities of stem cells or by charlatans peddling the modern equivalent of snake oil.”3

To read this article in its entirety please visit our website.

-Joseph S. Alpert, MD, Qin M. Chen, PhD

This article originally appeared in the September 2017 issue of The American Journal of Medicine.

Latest Posts

lupus

Sarcoidosis with Lupus Pernio in an Afro-Caribbean Man

A 54-year-old man of Afro-Caribbean ancestry presented with a 2-month history of nonproductive cough, 10-day history of constant subjective fevers, and a 1-day history...
Flue Vaccine

Flu Vaccination to Prevent Cardiovascular Mortality (video)

0
"Influenza can cause a significant burden on patients with coronary artery disease," write Barbetta et al in The American Journal of Medicine. For this...
varicella zoster

Varicella Zoster Virus-Induced Complete Heart Block

0
Complete heart block is usually caused by chronic myocardial ischemia and fibrosis but can also be induced by bacterial and viral infections. The varicella...
Racial justice in healthcare

Teaching Anti-Racism in the Clinical Environment

0
"Teaching Anti-Racism in the Clinical Environment: The Five-Minute Moment for Racial Justice in Healthcare" was originally published in the April 2023 issue of The...
Invisible hand of the market

The ‘Invisible Hand’ Doesn’t Work for Prescription Drugs

0
Pharmaceutical innovation has been responsible for many “miracles of modern medicine.” Reliance on the “invisible hand” of Adam Smith to allocate resources in the...
Joseph S. Alpert, MD

New Coronary Heart Disease Risk Factors

0
"New Coronary Heart Disease Risk Factors" by AJM Editor-in Chief Joseph S. Alpert, MD was originally published in the April 2023 issue of The...
Cardiovascular risk from noncardiac activities

Cardiac Risk Related to Noncardiac & Nonsurgical Activities

0
"Assessment of Cardiovascular Risk for Noncardiac and Nonsurgical Activities" was originally published in the April 2023 issue of The American Journal of Medicine. Cardiovascular risk...