Cellular cardiomyoplasty with human amniotic fluid stem cells: in vitro and in vivo studies.
Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n > or = 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, when compared with the saline injection group. Survival and proliferation of the transplanted hAFSCs were revealed by immunohistochemical staining. Expressions of the cardiac-specific markers such as Nkx2.5, alpha-actinin, and cardiac Troponin T were observed in the transplanted hAFSCs. Additionally, Cx43 was clearly expressed at the borders of the transplanted/transplanted and host/transplanted cells, an indication of enhancement of cell connection. The results demonstrated that hAFSCs induce angiogenesis, have cardiomyogenic potential, and may be used as a new cell source for cellular cardiomyoplasty.
Yeh
Yi-Chun
YC
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Wei
Hao-Ji
HJ
Lee
Wen-Yu
WY
Yu
Chu-Leng
CL
Chang
Yen
Y
Hsu
Li-Wen
LW
Chung
Min-Fan
MF
Tsai
Ming-Song
MS
Hwang
Shiaw-Min
SM
Sung
Hsing-Wen
HW
D000185:Actinin / Q000378:metabolism; D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D018421:Cardiomyoplasty / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D020107:Troponin T; D042461:Vascular Endothelial Growth Factor A; D000185:Actinin