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Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium
Open accessAbstract
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 10(6)) 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 10(6) 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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Cited by
Human mesenchymal stem cells modulate allogeneic immune cell responses
Aggarwal, S., & Pittenger, M. F. (2005) · Blood · doi:10.1182/blood-2004-04-1559 · Cited by 4,511
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Rasmusson, I. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.03.019 · Cited by 374
Milan, P. B., Lotfibakhshaiesh, N., Joghataie, M. T., Ai, J., Pazouki, A., Kaplan, D. L., Kargozar, S., Amini, N., Hamblin, M. R., Mozafari, M., et al. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.08.053 · Cited by 166
Immune properties of mesenchymal stem cells
Sotiropoulou, P. A., & Papamichail, M. (2007) · Methods in Molecular Biology · doi:10.1007/978-1-59745-536-7_16 · Cited by 57
Torres Crigna, A., Uhlig, S., Elvers-Hornung, S., Klüter, H., & Bieback, K. (2020) · Cells · doi:10.3390/cells9112419 · Cited by 46
Metadata
- Authors
- Grinnemo, K. H., Månsson, A., Dellgren, G., Klingberg, D., Wardell, E., Drvota, V, Tammik, C., Holgersson, J., Ringdén, O., Sylvén, C., & Le Blanc, K.
- Venue
- The Journal of Thoracic and Cardiovascular Surgery
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 127
- Issue
- 5
- Pages
- 1293-1300
- ISSN
- 0022-5223 (ISSN-L)
- OpenAlex
- W2031812736
- Cited by
- 294
- References
- 0
- FWCI
- 11.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Grinnemo, K. H., Månsson, A., Dellgren, G., Klingberg, D., Wardell, E., Drvota, V, Tammik, C., Holgersson, J., Ringdén, O., Sylvén, C., & Le Blanc, K. (2004). Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infarcted rat myocardium. The Journal of Thoracic and Cardiovascular Surgery. https://doi.org/10.1016/j.jtcvs.2003.07.037
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