Human Mesenchymal Stem Cells Differentiate to a Cardiomyocyte Phenotype in the Adult Murine Heart

TLDR

Cellular cardiomyoplasty has been proposed as an alternative strategy to augment function in diseased myocardium. The study examined whether adult bone marrow–derived hMSCs can differentiate into cardiomyocytes after transplantation into adult mouse hearts. hMSCs were isolated from healthy human donors, labeled with lacZ, and injected into the left ventricle of adult CB17 SCID/beige mice. Engrafted hMSCs survived beyond one week, acquired cardiomyocyte markers (desmin, β‑MHC, α‑actinin, cTnT, phospholamban) with sarcomeric organization, and did not express these markers in vitro, indicating in situ differentiation into cardiomyocytes.

Abstract

Background — Cellular cardiomyoplasty has been proposed as an alternative strategy for augmenting the function of diseased myocardium. We investigated the potential of human mesenchymal stem cells (hMSCs) from adult bone marrow to undergo myogenic differentiation once transplanted into the adult murine myocardium. Methods and Results — A small bone marrow aspirate was taken from the iliac crest of healthy human volunteers, and hMSCs were isolated as previously described. The stem cells, labeled with lacZ , were injected into the left ventricle of CB17 SCID/ beige adult mice. At 4 days after injection, none of the engrafted hMSCs expressed myogenic markers. A limited number of cells survived past 1 week and over time morphologically resembled the surrounding host cardiomyocytes. Immunohistochemistry revealed de novo expression of desmin, β-myosin heavy chain, α-actinin, cardiac troponin T, and phospholamban at levels comparable to those of the host cardiomyocytes; sarcomeric organization of the contractile proteins was observed. In comparison, neither cardiac troponin T nor phospholamban was detected in the myotubes formed in vitro by MyoD-transduced hMSCs. Conclusions — The purified hMSCs from adult bone marrow engrafted in the myocardium appeared to differentiate into cardiomyocytes. The persistence of the engrafted hMSCs and their in situ differentiation in the heart may represent the basis for using these adult stem cells for cellular cardiomyoplasty.