Epicardial deposition of endothelial progenitor and mesenchymal stem cells in a coated muscle patch after myocardial infarction in a murine model.
OBJECTIVE
To assess, using an in vivo engraftment strategy combining bone marrow cell (BMC) transplantation and tissue cardiomyoplasty, the functional outcome of distinct vascular progenitor cell therapy (endothelial progenitor (EPC) and mesenchymal stem (MSC) cells) at distance of myocardium infarction (MI). The study was also designed to test whether scaffold mixing progenitors with unfractionated BMC could improve progenitor recruitment in the damaged myocardium.


METHODS
To track engrafted progenitor cells in vivo, cultured murine MSC and EPC were transduced with eGFP lentiviruses. Thirty days after cryogenical induction of MI, C57BL/6J mice were randomized to receive muscle patch placement coated or not (control group), labeled EPC or MSC mixed to the ration of 1:10, or not with unfractionated BMC. Two weeks after transplantation, cardiac function was recorded and heart sections were examined to detect GFP-labeled progenitor cells and analyze cell differentiation.


RESULTS
This study showed that either type of mono cell therapy improved angiogenesis and cell survival in the scar but only MSC exhibited the capacity to invade the scar. We found no evidence of myocardial or vascular regeneration from progenitor cells. Engraftment of the progenitors/unfractionated BMC mix increased repopulation and thickness of the scar.


CONCLUSIONS
Combined therapy with unfractionated BMC and expanded MSC appeared thus promising for scar repopulation.
Derval
Nicolas
N
Cardiovascular Surgery and Cardiology Department, Hôpital Haut-Lévêque, Avenue de Magellan, Pessac 33604, France.
Barandon
Laurent
L
Dufourcq
Pascale
P
Leroux
Lionel
L
Lamazière
Jean-Marie Daniel
JM
Daret
Danièle
D
Couffinhal
Thierry
T
Duplàa
Cécile
C
D000009:Abdominal Muscles / Q000637:transplantation; D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006321:Heart / Q000502:physiology; D016130:Immunophenotyping; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D010496:Pericardium / Q000473:pathology*; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods*