Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages

Objectives: Marrow stromal cells are mesenchymal stem cells able to differe ntiate into cardiomyocytes in vitro. We tested the hypothesis that marrow s tromal cells, when implanted into myocardium, can undergo milieu-dependent differentiation and express cardiomyogenic phenotypes in vivo. Methods: Isogenic adult rats were used as donors and recipients to simulate autologous transplantation. Marrow stromal cells isolated from donor leg b ones were culture-expanded, labeled with 4',6-diamidino-2-phenylindole, and then injected into the myocardium of the recipients. The hearts were harve sted from 4 days to 12 weeks after implantation, and the implant sites were examined to identify the phenotypes of the labeled marrow stromal cells. Results: Viable cells labeled with 4',6-diamidino-2-phenylindole can be ide ntified in host myocardium at all time points after implantation. Implanted marrow stromal cells show the growth potential in a myocardial environment . After 4 weeks, donor cells derived from marrow stromal cells demonstrate myogenic differentiation with the expression of sarcomeric myosin heavy cha in and organized contractile proteins. Positive staining for connexin 43 in dicates the formation of gap junctions, which suggests that cells derived f rom marrow stromal cells, as well as native cardiomyocytes, are connected b y intercalated disks. Conclusions: Different cell sources have been used as donor cells for cellu lar cardiomyoplasty. Our findings indicate that marrow stromal cells can al so be used as donor cells. In an appropriate microenvironment they will exh ibit cardiomyogenic phenotypes and may replace native cardiomyocytes lost b y necrosis or apoptosis. Because marrow stromal cells can be obtained repea tedly by bone marrow aspiration and expanded vastly in vitro before being i mplanted or used as autologous implants, and because their use does not cal l for immunosuppression, the clinical use of marrow stromal cells for cellu lar cardiomyoplasty appears to be most advantageous.