G-CSF for stem cell therapy in acute myocardial infarction: friend or foe?
Stem cell-based therapy has emerged as a potential therapeutic option for patients with acute myocardial infarction. The ability of granulocyte colony-stimulating factor (G-CSF) to mobilize endogenous stem cells as well as to protect cardiomyocytes at risk via paracrine effects has attracted considerable attention. In the past decade, a number of clinical trials were carried out to study the efficacy of G-CSF in cardiac repair. These trials showed variable outcomes in terms of improved cardiac contractile function and suppressed left ventricular negative remodelling. Critical examinations of these results have raised doubts concerning the effectiveness of G-CSF in modulating functional recovery. However, these cumulative clinical experiences are helpful in the understanding of mechanisms and roles of signalling pathways in regulating homing and engraftment of bone marrow stem cells to the infarcted heart. In this review, we discuss some of the observations that may have influenced the clinical outcomes. Improving strategies that target the critical aspects of G-CSF-driven cardiac therapy may provide a better platform to augment clinical benefits in future trials.
Shim
Winston
W
Research and Development Unit, National Heart Centre Singapore , 17, Third Hospital Avenue, Mistri Wing, Singapore 168752. winston.shim.s.n@nhcs.com.sg
Mehta
Ashish
A
Lim
Sze Yun
SY
Zhang
Guangqin
G
Lim
Chong Hee
CH
Chua
Terrance
T
Wong
Philip
P
D053687:Adult Stem Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D000818:Animals; D002986:Clinical Trials as Topic; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D053612:Janus Kinases / Q000502:physiology; D008297:Male; D008955:Models, Cardiovascular; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects / Q000502:physiology
D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016179:Granulocyte Colony-Stimulating Factor; D053612:Janus Kinases