Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis (2024)

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Endothelial progenitor cells (EPCs) home to sites of tissue injury and differentiate into mature endothelial cells. Their transfer feasibility has been proven in models of hindlimb ischemia and myocardial infarction. We investigated, the effect of delivery of spleen-derived EPC in a rat model of inflammatory-mediated myocardial damage. Male Lewis rats (N=25) were immunized against myosin. Healthy donor Lewis rats were sacrificed, their spleens harvested, separated on Ficoll gradient centrifugation, and grown on fibronectin coated plates with endothelial cell medium for 5 days. Ten days after myosin immunization, spleen cell derived EPC were collected, and labeled 2 x 10(7) cells per rat were injected into the femoral vein of diseased rats. Cell transplantation was repeated twice, 2 and 4 weeks after initial cell transfer. Rats with inflammatory-mediated cardiomyopathy exhibited a significant mobilization of EPC from the bone marrow to the periphery and their ability to adhere to fib...

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Cardiosphere-Derived Cells Attenuate Inflammation, Preserve Systolic Function, and Prevent Adverse Remodeling in Rat Hearts With Experimental Autoimmune Myocarditis

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Despina Sanoudou

Background: Cardiosphere-derived cells (CDCs) have yielded promising efficacy signals in early-phase clinical trials of ischemic and nonischemic cardiomyopathy. The potential efficacy of CDCs in acute myocarditis, an inflammatory cardiomyopathy without effective therapy, remains unexplored. Given that CDCs produce regenerative, cardioprotective, anti-inflammatory, and anti-fibrotic effects (all of which could be beneficial in acute myocarditis), we investigated the efficacy of intracoronary delivery of CDCs in a rat model of experimental autoimmune myocarditis. Methods: Lewis rats underwent induction of experimental autoimmune myocarditis by subcutaneous footpad injection of purified porcine cardiac myosin supplemented with Mycobacterium tuberculosis on days 1 and 7. On day 10, rats were randomly assigned to receive global intracoronary delivery of 500 000 CDCs or vehicle. Global intracoronary delivery was performed by injection of cells or vehicle into the left ventricular (LV) cav...

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Journal of Molecular and Cellular Cardiology

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Human embryonic stem cell-derived cardiomyocytes survive and mature in the mouse heart and transiently improve function after myocardial infarction

2007 •

Krista Den Ouden

Regeneration of the myocardium by transplantation of cardiomyocytes is an emerging therapeutic strategy. Human embryonic stem cells (HESC) form cardiomyocytes readily but until recently at low efficiency, so that preclinical studies on transplantation in animals are only just beginning. Here, we show the results of the first long-term (12 weeks) analysis of the fate of HESC-derived cardiomyocytes transplanted intramyocardially into healthy, immunocompromised (NOD-SCID) mice and in NOD-SCID mice that had undergone myocardial infarction (MI). Transplantation of mixed populations of differentiated HESC containing 20-25% cardiomyocytes in control mice resulted in rapid formation of grafts in which the cardiomyocytes became organized and matured over time and the noncardiomyocyte population was lost. Grafts also formed in mice that had undergone MI. Four weeks after transplantation and MI, this resulted in significant improvement in cardiac function measured by magnetic resonance imaging...

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Journal of cellular and molecular medicine

Immuno-modification of enhancing stem cells targeting for myocardial repair

2015 •

Richard Sievers

Despite the controversy in mechanism, rodent and clinical studies have demonstrated beneficial effects of stem/progenitor cell therapy after myocardial infarction (MI). In a rat ischaemic reperfusion MI model, we investigated the effects of immunomodification of CD 34(+) cells on heart function and myocardial conduction. Bispecific antibody (BiAb), consisting of an anti-myosin light chain antibody and anti-CD45 antibody, injected intravenously was used to direct human CD34(+) cells to injured myocardium. Results were compared to echocardiography guided intramyocardial (IM) injection of CD34(+) cells and PBS injected intravenously. Treatment was administered 2 days post MI. Echocardiography was performed at 5 weeks and 3 months which demonstrated LV dilatation prevention and fractional shortening improvement in both the BiAb and IM injection approaches, with BiAb achieving better results. Histological analyses demonstrated a decrease in infarct size and increase in arteriogenesis in ...

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Successful implantation of intravenously administered stem cells correlates with severity of inflammation in murine myocarditis (2024)

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