A plant-derived remedy for repair of infarcted heart.
BACKGROUND
Myocardial infarction (MI) due to coronary artery disease remains one of the leading causes of premature death. Replacement of infarcted heart tissue with regenerating myocardium from endogenous progenitor pools or exogenously introduced stem cells remains a therapeutic ideal. Their impracticality mainly lies in their low efficiency in cardiogenic differentiation (CD). Our recent studies with an acute MI animal model have already demonstrated the therapeutic effect of the MeOH extract of Geum japonicum (EGJ), providing clear evidence of myocardial regeneration.


RESULTS
The present study further isolated the active component contained in EGJ using bioassay-guided isolation and investigated its efficacy in the treatment of infarcted heart in animal MI models. We demonstrated that substantial repair of infarcted heart in animal MI models by EGJ can be mimicked by the isolated candidate compound (cardiogenin) in MI animal models. Clear evidence of newly regenerated endogenous mesenchymal stem cells (MSCs) derived cardiomyocytes was observed throughout the infarct zone, accompanied by significantly improved functional performance of the heart. Transplantation of MSCs pretreated with EGJ or cardiogenin into a MI animal model also resulted in substantial regeneration of functional myocardium, implying that the activated MSCs carry all the necessary blueprints for myocardial regeneration. Signaling pathways specific to cell survival, CD identified in embryonic heart induction and angiogenesis were activated in both cardiogenin-treated MSCs and cardiogenin-induced regenerating myocardium.


CONCLUSIONS
This study has demonstrated the therapeutic effects of cardiogenin in infarcted heart repair, and identified the associated signalling pathways for effective cardiogenic differentiation of MSCs, cell survival and angiogenesis. These findings should enable new treatment strategies for MI to be developed immediately.
Cheng
Lei
L
Key Laboratory for Regenerative Medicine of Ministry of Education of China, The Chinese University of Hong Kong, Hong Kong SAR, China.
Chen
Hao
H
Yao
Xinsheng
X
Qi
Guoqing
G
Liu
Hongwei
H
Lee
Kwongman
K
Lee
Kaho
K
Zhang
Jieting
J
Chen
Shihui
S
Lin
Xiaoli
X
Zhao
Wenchao
W
Li
Jiankuan
J
Li
Ming
M
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004452:Echocardiography; D020869:Gene Expression Profiling; D031986:Geum; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D046228:Microarray Analysis; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology
D055415:Bone Morphogenetic Protein 4; D018994:Myosin Light Chains; D010936:Plant Extracts; D011993:Recombinant Fusion Proteins; D012503:Saponins; C539477:cardiogenin; C107184:myosin light chain 2; D024722:Cardiac Myosins