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. 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.
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. 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.
Authors: C L Ebens; J A McGrath; K Tamai; A Hovnanian; J E Wagner; M J Riddle; D R Keene; T E DeFor; R Tryon; M Chen; D T Woodley; K Hook; J Tolar Journal: Br J Dermatol Date: 2019-06-28 Impact factor: 9.302
Authors: Jakub Tolar; Akemi Ishida-Yamamoto; Megan Riddle; Ron T McElmurry; Mark Osborn; Lily Xia; Troy Lund; Catherine Slattery; Jouni Uitto; Angela M Christiano; John E Wagner; Bruce R Blazar Journal: Blood Date: 2008-10-27 Impact factor: 22.113
Authors: Steven L Highfill; Ryan M Kelly; Matthew J O'Shaughnessy; Qing Zhou; Lily Xia; Angela Panoskaltsis-Mortari; Patricia A Taylor; Jakub Tolar; Bruce R Blazar Journal: Blood Date: 2009-05-20 Impact factor: 22.113
Authors: Andrew Wilber; Fernando Ulloa Montoya; Luke Hammer; Branden S Moriarity; Aron M Geurts; David A Largaespada; Catherine M Verfaillie; R Scott McIvor; Uma Lakshmipathy Journal: Stem Cells Int Date: 2011-10-02 Impact factor: 5.443