Eric Daniels

Expression of cardiomyocytic markers on adipose tissue-derived cells in a murine model of acute myocardial injury

Animal and early clinical studies have provided evidence suggesting that intracoronary administration of autologous bone marrow-derived cells results in improved outcome following myocardial infarction. Animal studies with cultured marrow stromal cells (MSC) have provided similar data. Cells with properties that are similar to MSC have been identified in adipose tissue. Other groups have demonstrated in vivo differentiation of adipose tissue-derived cells (ADC) into cells exhibiting biochemical and functional markers of cardiac myocytes, including spontaneous beating. Based on these observations, the objective of the present study was to determine whether ADC might undergo similar differentiation in vivo in the context of myocardial injury.ADC were isolated from subcutaneous adipose tissue of Rosa26 mice (which express the beta-galactosidase transgene in almost every tissue) and injected into the intraventricular chamber of B6129S recipient mice immediately following induction of myocardial cryoinjury. Groups of recipients were euthanized at 24 hours, 7 and 14 days post surgery and examined for the presence of donor-derived cells within the heart.Beta-gal positive cells were identified in the infarcts of ADC-treated animals. No staining was observed in uninjured myocardium or in infarcts of control animals. Immunohistochemical analysis revealed co-expression of beta-gal with Myosin Heavy Chain, Nkx2.5 and with Troponin I. Co-expression of beta-galactosidase with Connexin 43, CD31, von Willebrand factor, MyoD or CD45 was not detected.Thus, these data indicate that adipose tissue contains a population of cells that has the ability to engraft injured myocardium and that this engraftment is associated with expression of cardiomyocytic markers by donor-derived cells.

The use of adult stem cells in regenerative medicine

The cellular component of the tissue engineering paradigm is arguably the most important piece of the complex task of regenerating or repairing damaged or diseased tissue. Critical to the development of clinical strategies is the need for reliable sources of multipotent cells that can be obtained with limited morbidity. The adult stem cell population may be well suited for this task. The next several years will bring many phase I and II studies using adult stem cells as the cellular foundation for engineered tissue constructs. Future research should be directed toward better characterization of this cell population, including identifying unique markers and mapping out lineage development. For now, the ideal source of adult stem cells remains uncertain, but as questions are answered, adult stem cell biology will likely transition from bench top to clinical reality.