Allogeneic Mesenchymal Stromal Cells Transplanted Onto the Heart Surface Achieve Therapeutic Myocardial Repair Despite Immunologic Responses in Rats

Autor: Yasunori Shintani, Kenta Yashiro, Ken Suzuki, Anthony N. Warrens, Masahiro Kaneko, Nobuko Tano, Manabu Shiraishi, Chiho Ikebe, Steven R. Coppen, Yuki Ichihara
Rok vydání: 2016
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Graft Rejection
Male
Time Factors
Translational Studies
medicine.medical_treatment
Myocardial Infarction
heart failure
Ventricular Function
Left
Myocardial infarction
Cells
Cultured
mesenchymal stem cell
Original Research
Cardiovascular Surgery
biology
Graft Survival
immunologic response
Cardiology and Cardiovascular Medicine
Cell Survival
Mesenchymal Stem Cell Transplantation
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
Regeneration
Transplantation
Homologous
Interleukin 6
cell transplantation
business.industry
Interleukin-6
Regeneration (biology)
Myocardium
Mesenchymal stem cell
Cell Therapy
Mesenchymal Stem Cells
Stroke Volume
Recovery of Function
medicine.disease
Rats
Inbred F344
Transplantation
Disease Models
Animal
030104 developmental biology
allotransplantation
Rats
Inbred Lew
Heart failure
Immunology
biology.protein
Cancer research
business
Allotransplantation
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: Background Transplantation of allogeneic mesenchymal stromal cells ( MSC s) 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 MSC s have been suggested, allogeneic MSC s transplanted on the heart surface (virtual space) may undergo different courses. This study aimed to elucidate immunologic response against epicardially placed allogeneic MSC s, rejection or acceptance of these cells, and their therapeutic effects for heart failure. 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 MSC s survived on the heart surface in both MSC sheet groups. By day 28, survival of syngeneic MSC s was substantially reduced (8.9%); survival of allogeneic MSC s was more extensively reduced (0.2%), suggesting allorejection. Correspondingly, allogeneic MSC s were found to have evoked an immunologic response, albeit low level, as characterized by accumulation of CD 4 + 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. Conclusions Allogeneic MSC s 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 MSC s. Further development of this approach toward clinical application is warranted.
Databáze: OpenAIRE
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