Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation

By K. Hatzistergos, Henry C. Quevedo, Behzad N. Oskouei, Qinghua Hu, Gary S. Feigenbaum, Irene S. Margitich, R. Mazhari, A. Boyle, J. Zambrano, Jose E Rodriguez and 7 more. Circulation Research, 2010

713 citations recorded by the source corpus.

Rationale: 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. Objective: 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. Methods And Results: 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. Conclusions: MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics.

Subfields: Genetics, Molecular Biology, Surgery

View Paper: https://www.semanticscholar.org/paper/d424560aaf6b9542681a99f2cbaf0366d5a0a634

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In Genetics

1. J. Karp
2. A. Caplan
3. Andrea Augello
4. C. De Bari
5. D. Prockop

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Citations in the corpus

• Harnessing the Mesenchymal Stem Cell Secretome for the Treatment of Cardiovascular Disease (2012, background): “…potential mechanisms for how exogenous-culture-expanded MSCs may contribute to cardiovascular repair: MSC transdifferentiation into cardiomyocytes (Hatzistergos et al., 2010), fusion of MSCs with native cells (Noiseux et al., 2006), MSC-induced stimulation of endogenous CSCs via direct cell-cell…”
• Comparison of Allogeneic vs Autologous Bone Marrow–Derived Mesenchymal Stem Cells Delivered by Transendocardial Injection in Patients With Ischemic Cardiomyopathy (2012, background): “entiation, but also by stimulating endogenous cardiac stem cells to proliferate, undergo lineage commitment, and form transient amplifying cells.(32,44) Our pilot study is limited primarily by the lack of a placebo group and its open-label design.”
• Mesenchymal stem cell perspective: cell biology to clinical progress (2019, background): “Numerous preclinical and clinical trials have demonstrated that injection of MSCs into the border zone between infarcted and viable cardiac tissue results in a powerful antifibrotic effect, reduced tissue injury and augmentation of viable and perfused tissue.141–145 The improved contractile cardiac ”