Cardiac repair with injectable cell sheet fragments of human amniotic fluid stem cells in an immune-suppressed rat model.
Direct intramyocardial injection of the desired cell types in a dissociated form is a common route of cell transplantation for repair of damaged myocardium. However, following injection of dissociated cells, a massive loss of transplanted cells has been reported. In this study, human amniotic fluid stem cells (hAFSCs) were used as the cell source for the fabrication of cell sheet fragments, using a thermo-responsive methylcellulose hydrogel system. The fabricated hAFSC sheet fragments preserved the endogenous extracellular matrices (ECM) and retained their cell phenotype. Test samples were xenogenically transplanted into the peri-ischemic area of an immune-suppressed rat model at 1 week after myocardial infarction (MI) induction. There were four treatment groups (n>=10): sham; saline; dissociated hAFSCs; and hAFSC sheet fragments. The results obtained in the echocardiography revealed that the group treated with hAFSC sheet fragments had a superior heart function to those treated with saline or dissociated hAFSCs. Due to their inherent ECM, hAFSC sheet fragments had a better ability of cell retention and proliferation than dissociated hAFSCs upon transplantation to the host myocardium. Additionally, transplantation of hAFSC sheet fragments stimulated a significant increase in vascular density, consequently contributing towards improved wall thickness and a reduction in the infarct size, when compared with dissociated hAFSCs. Our histological findings and qPCR analyses suggest that the transplanted hAFSCs can be differentiated into cardiomyocyte-like cells and cells of endothelial lineages and modulate expression of multiple angiogenic cytokines and cardiac protective factor with the potential to promote neo-vascularization, which evidently contributed to the improvement of ventricular function.
Yeh
Yi-Chun
YC
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, ROC.
Lee
Wen-Yu
WY
Yu
Chu-Leng
CL
Hwang
Shiaw-Min
SM
Chung
Min-Fan
MF
Hsu
Li-Wen
LW
Chang
Yen
Y
Lin
Wei-Wen
WW
Tsai
Ming-Song
MS
Wei
Hao-Ji
HJ
Sung
Hsing-Wen
HW
D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D007165:Immunosuppression Therapy; D007267:Injections; D008747:Methylcellulose / Q000737:chemistry; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology; D018919:Neovascularization, Physiologic; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000166:cytology*
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D008747:Methylcellulose