Ann Thorac Surg 2002;74:24
© 2002 The Society of Thoracic Surgeons
Original article: cardiovascular
Invited commentary
David K.C. Cooper, MDa
a Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA
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In this very interesting paper from Dr Ray Chiu’s group, Saito and colleagues report that intravenously-injected mouse bone marrow stromal cells successfully engrafted into the bone marrow of rats in the absence of any immunosuppressive therapy. Furthermore, following ligation of one of the rat’s coronary arteries, mouse cells could be detected in the infarcted myocardium. In similarly treated rats that had not undergone coronary ligation, mouse cells could not be identified in the heart. The conclusion drawn is that the marrow stromal cells were adult stem cells with a unique tolerance to immunologic injury. This allowed their engraftment in a xenogeneic environment while preserving their ability to be recruited to an injured myocardium (via the bloodstream) and to undergo differentiation to form a stable cardiac chimera. These results are certainly remarkable but, as with all experimental studies, leave many questions unanswered.
How did the mouse cells escape immunologic injury? The authors invoke the "danger model" hypothesis that is currently topical, and suggest that the cells might not have presented "danger signals" to the rat recipient, and thus escaped immune destruction. However, one would anticipate that the presence of any foreign cells would be interpreted by the host as being potentially dangerous. Why were xenogeneic cells chosen for infusion, and not allogeneic or autologous cells? The authors discuss the logistic disadvantages of the use of autologous cells, but do not adequately explain why they chose xenogeneic over allogeneic cells. One could hypothesize that xenogeneic cells are so different that they escape an immune response, but this has not been the case in other mouse-to-rat models. Their failure to be injured by the host, therefore, must presumably be related to the nature of the "stem cells" used. Was the number of mouse cells detected in the infarcted rat myocardium sufficient to have a clinically-useful effect on its recovery or on the strength of its coordinated myocardial contractions? No truly quantitative data are provided but, from the paper’s excellent histochemical figures, the answer is "probably not." Nevertheless, despite the intriguing and, as yet, unanswered questions, the study provides some encouragement that we shall one day not only be able to treat myocardial infarction by a cell therapy approach, but that we may also be able to overcome the barriers to xenotransplantation.
Related Article
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Xenotransplant cardiac chimera: immune tolerance of adult stem cells
- Takayuki Saito, Jin-Qiang Kuang, Bindu Bittira, Abdulaziz Al-Khaldi, and Ray C.-J. Chiu
Ann. Thorac. Surg. 2002 74: 19-24.
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