In the adult mesenchymal stem cell population, source gender is a biologically relevant aspect of protective power.
BACKGROUND
Acute treatment with bone marrow mesenchymal stem cells (MSC) reduces myocardial infarct size by multiple mechanisms, including the paracrine release of protective growth factors. Female MSCs produce more growth factor when stressed; therefore, we hypothesized that myocardial protection provoked by female MSCs would be greater than that elicited by male MSCs.


METHODS
Hearts were subjected to 25 min of warm global ischemia, 40 min of reperfusion, and randomly assigned into one of three groups: (1) vehicle treated; (2) male MSC treated; and (3) female MSC treated. Myocardial function was continuously recorded and in separate experiments, male and female MSC growth factor production was assessed by ELISA.


RESULTS
All indices of functional recovery were significantly higher in the stem cell infused rat heart compared with control hearts. Interestingly, female MSC treated rat hearts demonstrated significantly greater recovery of left ventricular developed pressure, +dP/dT, and -dP/dT than male MSC treated hearts at end reperfusion. In addition, male MSCs produced significantly greater tumor necrosis factor alpha, and significantly less vascular endothelial growth factor than female MSCs.


CONCLUSIONS
This study is the first to demonstrate that, in the adult mesenchymal population, source gender is a biologically relevant aspect of ultimate stem cell function in the heart.
Crisostomo
Paul R
PR
Department of Surgery, Indiana University School of Medicine, Indianapolis, Ind, USA. pcrisost@iupui.edu
Markel
Troy A
TA
Wang
Meijing
M
Lahm
Tim
T
Lillemoe
Keith D
KD
Meldrum
Daniel R
DR
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A