Contribution of Mesenchymal Progenitor Cells to Tissue Repair in Rat Cardiac Allografts Undergoing Chronic Rejection
| Autor: | Noboru Mitsuhashi, Gordon D. Wu, Lora Barsky, Mark L. Barr, Hui Zhu, Michael E. Bowdish, Yang-Sun Jin |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Graft Rejection
Pulmonary and Respiratory Medicine Transplantation Heterotopic Green Fluorescent Proteins Biology Mesenchymal Stem Cell Transplantation Cell Movement Genes Reporter Transduction Genetic medicine Animals Regeneration Transplantation Homologous Myocytes Cardiac Progenitor cell Fibroblast Transplantation Reverse Transcriptase Polymerase Chain Reaction Myogenesis Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Fibroblasts Flow Cytometry Immunohistochemistry Rats Inbred F344 Rats Cell biology Retroviridae medicine.anatomical_structure Rats Inbred Lew Chronic Disease Immunology Heart Transplantation Surgery Bone marrow Cardiology and Cardiovascular Medicine Myofibroblast Homing (hematopoietic) Transforming growth factor |
| Zdroj: | The Journal of Heart and Lung Transplantation. 24:2160-2169 |
| ISSN: | 1053-2498 |
| Popis: | Background Mesenchymal progenitor cells (MPC) have recently been demonstrated to actively migrate into cardiac allografts during chronic rejection. This study examines the role of MPC in tissue repair of heart allografts in a rat model of chronic rejection. Methods The potential of a rat MPC line (Ap8c3) to differentiate to myofibroblasts and cardiomyocytes was studied in differentiation cultures. Ap8c3 cells tagged with an enhanced green fluorescent protein (eGFP) reporter gene were engrafted into Fischer 344 (F344) recipients of Lewis (LEW) cardiac allografts. Development of intragraft MPC into scar-forming fibroblasts and cardiomyocytes was studied using immunohistochemistry. Results Ap8c3 cells contain fibroblast progenitors (FP) positive for P07 antibody. Transforming growth factor (TGF)-β stimulation promoted FP to terminally differentiate into myofibroblasts, which express α-smooth muscle actin (αSMA). In cardiac differentiation culture, Ap8c3 cells were induced by 5-azatiditin (5-aza) to form tropomyosin + myotubes, and to express mRNA encoding for cardiac troponin I (TnI) and α-myosin heavy chain (αMHC). Transfusion of eGFP + Ap8c3 cells to F344 recipients resulted in migration of eGFP + cells into LEW heart allografts, as well as homing of the eGFP + MPC to bone marrow. The majority of eGFP + cells in the heart allografts appeared to be vimentin-expressing fibroblasts. Foci of eGFP + myocardium were also detected in all heart allografts, with eGFP + cardiomyocytes representing 4.8 ± 1.2% of the allografted eGFP + cells. Conclusions The data suggest that rat MPC participate in tissue repair in heart allografts by giving rise to scar-forming myofibroblasts and cardiomyocytes. |
| Databáze: | OpenAIRE |
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