biostudies-literatureHatzistergos KENIA NIH HHSNHLBI NIH HHS913-22https://www.ebi.ac.uk/biostudies/studies/S-EPMC3408082biostudies-literatureUnknown107(7)The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes.Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire.Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I.MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.Circulation researchBone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.PMC3408082U54-HL081028HL065455R01-HL084275R01 HL094849-01HL094849P20 HL101443-01U54 HL081028U54 HL081028-01R01 HL094849R01 HL084275-01A2R01 HL065455R01 AG025017R01 HL084275R01 HL065455-01R01 AG025017-01P20 HL101443Dulce RMargitich ISHatzistergos KEQuevedo HOskouei BNZambrano JPMcNiece IValdes DPattany PMMazhari RRevilla CHare JMHeldman AWHu QFeigenbaum GSBoyle AJRodriguez JEfalseBone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes.Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire.Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit(+) CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4(+) CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit(+) CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I.MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.2010-01-01T00:00:00Z2010 Oct2020-10-31T09:18:31Z2019-03-26T23:49:24ZS-EPMC34080822067123810.1161/circresaha.110.22270310.1161/CIRCRESAHA.110.222703