In vitro preprogramming of marrow stromal cells for myocardial regeneration.
Ann Thorac Surg
; 74(4): 1154-9; discussion 1159-60, 2002 Oct.
Article
em En
| MEDLINE
| ID: mdl-12400761
ABSTRACT
BACKGROUND:
We have previously reported that marrow stromal stem cells (MSCs), when implanted into myocardium, can undergo milieu-dependent differentiation to express phenotypes similar to the cells in the immediate microenvironment. We tested the hypothesis that by in vitro preprogramming of MSCs, we may be able to guide their differentiation to express a therapeutically desirable phenotype that is different from those in their microenvironment.METHODS:
MSCs were isolated from isogenic Lewis rats, culture expanded, and labeled with beta-gal using retrovirus carrying the lac-Z gene. A subset of the transfected MSCs was then treated with 5-aza-2'deoxycytidine (5-aza). Three weeks after the left ventricles were cryoinjured, either 5-aza-pretreated (n = 10) or untreated (n = 8) MSCs were injected into the myocardial scar. The hearts were harvested 4 to 8 weeks later and stained immunohistochemically for phenotypic markers.RESULTS:
The labeled MSCs within the scars that were 5-aza pretreated appeared to be morphologically distinct from the untreated ones. The treated cells (8/10 rats) appeared more myotube-like, with elongated nuclei, linearly aligned with one another, and stained positive for the cardiomyocyte-specific marker troponin I-C. Untreated MSCs (5/8 rats), in contrast, were poorly differentiated, and some appeared to express other phenotypes seen in the scar tissue.CONCLUSIONS:
Our findings indicate that in cellular cardiomyoplasty using MSCs, one may select different strategies to achieve specific therapeutic goals. By milieu-dependent differentiation, unmodified MSCs may augment myocardial angiogenesis and myogenesis, whereas converting scar into myogenic tissue may be facilitated by preprogramming of MSCs before implantation.
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Base de dados:
MEDLINE
Assunto principal:
Regeneração
/
Células da Medula Óssea
/
Coração
Limite:
Animals
Idioma:
En
Revista:
Ann Thorac Surg
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Canadá