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J Thorac Cardiovasc Surg 2004;127:1293-1300
© 2004 The American Association for Thoracic Surgery
Cardiopulmonary support and physiology |
a Department of Cardiothoracic Surgery and Anaesthesiology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
b Department of Cardiology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
c Department of Clinical Immunology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
d Center for Allogenic Stem Cell Transplantation and Clinical Research Center, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden
Received for publication November 6, 2002; revisions received June 13, 2003; accepted for publication July 13, 2003.
* Address for reprints: Göran Dellgren, MD, Departments of Cardiothoracic Surgery and Anaesthesiology, Huddinge University Hospital, S-141 86 Stockholm, Sweden
goran.dellgren{at}thsurg.hs.sll.se
OBJECTIVE: It is thought that adult human mesenchymal stem cells do not induce immunoreactivity even to xenografts. We wanted to study whether adult human mesenchymal stem cells survive and engraft in experimentally induced ischemic rat myocardium.
METHODS: Bone marrow–derived adult human mesenchymal stem cells (2.5 x 106) were injected into the myocardium of 4 Sprague-Dawley rats. One week after injection, peripheral blood rat lymphocytes were added to adult human mesenchymal stem cells in a mixed lymphocyte reaction. Furthermore, an infarction was created by left anterior descending artery ligation of 8 Sprague-Dawley rats, 4 of which were immunosuppressed with tacrolimus (0.1 mg/kg/d) and 4 RNU athymic rats. One week after left anterior descending artery ligation, 2.5 to 3.5 x 106 adult human mesenchymal stem cells were injected around the infarcted area. The adult human mesenchymal stem cells were identified with fluorescence in situ hybridization technique and myocardial antigens by immunohistochemistry. The immune response was studied by hematoxylin and eosin staining and by antibodies directed toward macrophages.
RESULTS: Significant rat lymphocyte proliferation was observed when adult human mesenchymal stem cells were added to peripheral blood from Sprague-Dawley rats previously exposed to adult human mesenchymal stem cells. No reactivity was seen in lymphocytes from untreated Sprague-Dawley rats and athymic rats. Adult human mesenchymal stem cells could only be identified in the myocardium of athymic rats. Further, in normal Sprague-Dawley rats, there was a significant myocardial infiltration of round cells, mostly macrophages, in the area of injection of adult human mesenchymal stem cells. In RNU rats, this reaction was less intense.
CONCLUSION: Adult human mesenchymal stem cells did not induce xenoreactivity in vitro in previously unexposed immunocompetent Sprague-Dawley rats. However, although mesenchymal stem cells are transplantable across allogeneic barriers, transplant rejection can occur in a xenogenic model. When transplanted into an immunoincompetent host, adult human mesenchymal stem cells showed persistent engraftment.
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