Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation.
Circ Res
; 107(7): 913-22, 2010 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-20671238
ABSTRACT
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 ANDRESULTS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myocytes, Cardiac
/
Mesenchymal Stem Cell Transplantation
/
Mesenchymal Stem Cells
/
Myocardial Infarction
Limits:
Animals
Language:
En
Journal:
Circ Res
Year:
2010
Type:
Article
Affiliation country:
United States