Editors' ChoiceStem Cells

Your Cells or Mine?

See allHide authors and affiliations

Science Translational Medicine  12 Dec 2012:
Vol. 4, Issue 164, pp. 164ec227
DOI: 10.1126/scitranslmed.3005445

Bone marrow–derived mesenchymal stem cells (MSCs) are being studied as a potential therapy for a wide range of diseases, from graft-versus-host disease to acute lung injury to myocardial infarction. MSCs are thought to be “immunoprivileged” due in part to their lack of expression of major histocompatibility class II antigens and do not require matching prior to administration. However, there has been some concern that use of allogeneic MSCs could provoke alloimmunization and thus limit the cells’ long-term therapeutic efficacy. On the other hand, unlike autologous MSCs, which need to be harvested from the patient’s own bone marrow and expanded in tissue culture before transplantation, allogeneic MSCs can be prepared in advance from healthy unrelated donors and thus may be a more feasible therapeutic option in urgent or emergent situations. Against this backdrop, Hare and colleagues set out to compare allogeneic and autologous MSCs for the treatment of ischemic cardiomyopathy (weakness of the heart muscle due to chronic coronary artery disease) in a phase I/II study.

In this small study, 31 patients with ischemic cardiomyopathy were randomized to receive either autologous or allogeneic MSCs at a range of doses via transendocardial injection. There was no difference between the two groups in the primary endpoint, the 30-day incidence of treatment-emergent serious adverse events (SAEs). Likewise, after 1 year there was no difference in the rate of SAEs between the two groups, although the numeric trends favored the allogeneic group in most categories (such as rate of arrhythmias). Autologous MSCs improved the distance walked in 6 min and quality-of-life scores, and both autologous and allogeneic cells improved some echocardiographic measures of left ventricular remodeling (although not function). Importantly, allogeneic MSCs did not seem to provoke substantial alloimmunization, nor was there any evidence of ectopic tissue formation or tumorigenicity 1 year after transplantation.

The field of cell-based therapies is still in its infancy, and many important questions about the optimal approach to therapy remain unanswered. Although the treatment effects observed in this phase I/II trial were not particularly dramatic and the trial was not powered to provide conclusive evidence of safety, the Hare et al. study shows that both allogeneic and autologous MSCs may have potential as cellular therapies for treating ischemic cardiomyopathy. Given the promising preclinical data for MSCs in many settings, larger-scale clinical studies are warranted to provide more definitive evidence of both their safety and efficacy.

J. M. Hare et al., Comparison of allogeneic vs autologous bone marrow-derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: The POSEIDON randomized trial. JAMA, published online 6 November 2012 (10.1001/jama.2012.25321). [PubMed]

Stay Connected to Science Translational Medicine

Navigate This Article