Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages.
OBJECTIVE
Marrow stromal cells are mesenchymal stem cells able to differentiate into cardiomyocytes in vitro. We tested the hypothesis that marrow stromal 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 bones were culture-expanded, labeled with 4;,6-diamidino-2-phenylindole, and then injected into the myocardium of the recipients. The hearts were harvested 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 identified 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 chain and organized contractile proteins. Positive staining for connexin 43 indicates the formation of gap junctions, which suggests that cells derived from marrow stromal cells, as well as native cardiomyocytes, are connected by intercalated disks.


CONCLUSIONS
Different cell sources have been used as donor cells for cellular cardiomyoplasty. Our findings indicate that marrow stromal cells can also be used as donor cells. In an appropriate microenvironment they will exhibit cardiomyogenic phenotypes and may replace native cardiomyocytes lost by necrosis or apoptosis. Because marrow stromal cells can be obtained repeatedly by bone marrow aspiration and expanded vastly in vitro before being implanted or used as autologous implants, and because their use does not call for immunosuppression, the clinical use of marrow stromal cells for cellular cardiomyoplasty appears to be most advantageous.
Wang
J S
JS
Division of Cardiothoracic Surgery, McGill University, the Division of Hematology Oncology, Jewish General Hospital/McGill University, Montreal, Quebec, Canada.
Shum-Tim
D
D
Galipeau
J
J
Chedrawy
E
E
Eliopoulos
N
N
Chiu
R C
RC
D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000166:cytology*; D010641:Phenotype; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling / Q000379:methods; D014182:Transplantation, Autologous