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Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats.
- Source :
-
Journal of the American Heart Association [J Am Heart Assoc] 2016 Feb 18; Vol. 5 (2). Date of Electronic Publication: 2016 Feb 18. - Publication Year :
- 2016
-
Abstract
- Background: Transplantation of allogeneic mesenchymal stromal cells (MSCs) is a promising treatment for heart failure. We have shown that epicardial placement of cell sheets markedly increases donor cell survival and augments therapeutic effects compared with the current methods. Although immune rejection of intramyocardially injected allogeneic MSCs have been suggested, allogeneic MSCs transplanted on the heart surface (virtual space) may undergo different courses. This study aimed to elucidate immunologic response against epicardially placed allogeneic MSCs, rejection or acceptance of these cells, and their therapeutic effects for heart failure.<br />Methods and Results: At 4 weeks after coronary artery ligation, Lewis rats underwent epicardial placement of MSC sheets from syngeneic Lewis or allogeneic Fischer 344 rats or sham treatment. At days 3 and 10 after treatment, similar ratios (≈50% and 30%, respectively) of grafted MSCs survived on the heart surface in both MSC sheet groups. By day 28, survival of syngeneic MSCs was substantially reduced (8.9%); survival of allogeneic MSCs was more extensively reduced (0.2%), suggesting allorejection. Correspondingly, allogeneic MSCs were found to have evoked an immunologic response, albeit low level, as characterized by accumulation of CD4(+) T cells and upregulation of interleukin 6. Despite this alloimmune response, the allogeneic MSC sheet achieved myocardial upregulation of reparative factors, enhanced repair of the failing myocardium, and improved cardiac function to the equivalent degree observed for the syngeneic MSC sheet.<br />Conclusions: Allogeneic MSCs placed on the heart surface evoked an immunologic response; however, this allowed sufficient early phase donor cell survival to induce equivalent therapeutic benefits to syngeneic MSCs. Further development of this approach toward clinical application is warranted.<br /> (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)
- Subjects :
- Animals
CD4-Positive T-Lymphocytes immunology
Cell Survival
Cells, Cultured
Disease Models, Animal
Graft Rejection immunology
Graft Survival
Heart Failure immunology
Heart Failure pathology
Heart Failure physiopathology
Interleukin-6 immunology
Male
Myocardial Infarction immunology
Myocardial Infarction pathology
Myocardial Infarction physiopathology
Myocardium pathology
Rats, Inbred F344
Rats, Inbred Lew
Recovery of Function
Stroke Volume
Time Factors
Transplantation, Homologous
Ventricular Function, Left
Heart Failure surgery
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells immunology
Myocardial Infarction surgery
Myocardium immunology
Regeneration
Subjects
Details
- Language :
- English
- ISSN :
- 2047-9980
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of the American Heart Association
- Publication Type :
- Academic Journal
- Accession number :
- 26896478
- Full Text :
- https://doi.org/10.1161/JAHA.115.002815