TY - JOUR
T1 - The host immune response is essential for the beneficial effect of adult stem cells after myocardial ischemia
AU - Tolar, Jakub
AU - Wang, Xiaohong
AU - Braunlin, Elizabeth
AU - McElmurry, Ron T.
AU - Nakamura, Yasuhiro
AU - Bell, Scott
AU - Xia, Lily
AU - Zhang, John
AU - Hu, Qingsong
AU - Panoskaltsis-Mortari, Angela
AU - Zhang, Jianyi
AU - Blazar, Bruce R.
N1 - Funding Information:
This work was supported in part by American Heart Association Scientist Development Grant and Children's Cancer Research Fund (J.T.); National Institutes of Health (NIH) grants RO1 HL67828 (J.Z.), RO1 HL71970 (J.Z.), RO1 HL55209 (B.R.B.), RO1 HL52952 and RO1 HL49997 (B.R.B.). Authors declare no conflicts of interest.
PY - 2007/4
Y1 - 2007/4
N2 - 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-2Rγc-/- 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-2Rγc-/- 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-2Rγc-/- 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. Conclusion: 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.
AB - 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-2Rγc-/- 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-2Rγc-/- 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-2Rγc-/- 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. Conclusion: 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.
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U2 - 10.1016/j.exphem.2006.12.005
DO - 10.1016/j.exphem.2006.12.005
M3 - Article
C2 - 17379078
AN - SCOPUS:33947331495
SN - 0301-472X
VL - 35
SP - 682
EP - 690
JO - Experimental Hematology
JF - Experimental Hematology
IS - 4
ER -
