The host immune response is essential for the beneficial effect of adult stem cells after myocardial ischemia.
OBJECTIVE
Multipotent adult progenitor cells (MAPCs) are adult stem cells derived from bone marrow. We investigated the capacity of MAPCs to aid in tissue healing after myocardial ischemia in mice with different levels of immune competence.


METHODS
Adult murine C57BL/6 MAPCs were labeled with firefly luciferase and DsRed2 fluorescent protein and injected into the myocardium of immunocompetent C57BL/6 or T-, B- and natural killer-cell severe combined immunodeficient C57BL/6 Rag2/IL-2Rgammac(-/-) mice at the time of myocardial infarction (MI). Mice were sequentially analyzed using in vivo whole body bioluminescent imaging for MAPC persistence and high-resolution ultrasound biomicroscopy to assess cardiac function.


RESULTS
Luciferase signals emitted from donor MAPCs were significantly higher in Rag2/IL-2Rgammac(-/-) mice compared with C57BL/6 recipients of labeled MAPCs. At 100, 200, and 365 days after MI, left ventricular contractile function was significantly improved (and normalized) in C57BL/6 MAPC recipients. In contrast, despite a greater degree of MAPC persistence compared with C57BL/6 recipients, no cardiac improvement occurred in Rag2/IL-2Rgammac(-/-) recipients of MAPCs. The improved cardiac contractile performance in response to syngeneic MAPC infusion correlated with a prominent increase of vascular density in infarcted and peri-infarcted myocardium, which was dependent upon host immune competency.


CONCLUSIONS
These data indicate that immune competence of the recipient modulates the therapeutic impact of the adult nonhematopoietic stem cells infused after acute MI injury and that a more vigorous immune response is advantageous for therapeutic myocardial repair after MI.
Tolar
Jakub
J
Cancer Center and Department of Pediatrics, Division of Hematology-Oncology, Blood and Marrow Transplantation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA. tolar003@umn.edu
Wang
Xiaohong
X
Braunlin
Elizabeth
E
McElmurry
Ron T
RT
Nakamura
Yasuhiro
Y
Bell
Scott
S
Xia
Lily
L
Zhang
John
J
Hu
Qingsong
Q
Panoskaltsis-Mortari
Angela
A
Zhang
Jianyi
J
Blazar
Bruce R
BR
D053687:Adult Stem Cells; D000818:Animals; D017690:Cell Transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D017202:Myocardial Ischemia / Q000276:immunology / Q000628:therapy*