Stem cells for cardiac regeneration and possible roles of the transforming growth factor-β superfamily

Abstract

Heart failure is a leading cause of death worldwide. Studies of stem cell biology are essential for developing efficient treatments. Recently, we established and characterized c-kit-positive cardiac stem cells from the adult rat heart. Using a MethoCult culture system with a methyl-cellulose-based medium, stem-like left-atrium-derived pluripotent cells could be regulated to differentiate into skeletal/cardiac myocytes or adipocytes with almost 100% purity. Microarray and pathway analyses of these cells showed that transforming growth factor-β1 (TGF-β1) and noggin were significantly involved in the differentiation switch. Furthermore, TGF-β1 may act as a regulator for this switch because it simultaneously inhibits adipogenesis and activates myogenesis in a dose-dependent manner. However, the effect of TGF-β varies with developmental stage, dosage, and timing of treatment. In the present review, the findings of recent studies, in particular the use of c-kit-positive cardiac stem cells, are discussed. The effects of the TGF-β superfamily on differentiation, especially on adipogenesis and/or myogenesis, have important implications for future regenerative medicine.

Cell Shape and Cardiosphere Differentiation: A Revelation by Proteomic Profiling

“…Makkar et al reported that cardiosphere-derived cells were used for phase 1 clinical trials, and they warrant a phase 2 study [42]. Readers can refer to review articles for details about other types of cardiac stem cells [21, 22, 43–48]. …”

“…In human biopsies, 80% of cardiosphere-derived stem cells from the myocardial infarcted patients were c-kit and MDR-1 double positive [64]. The role of c-kit may change according to its expression level [22]. …”

3D-Culture System for Heart Regeneration and Cardiac Medicine

“…Furthermore, the addition of noggin resulted in the downregulation of adipogenesis and produced high yields of beating cardiomyocytes. Further discussion regarding the results of this report has been described elsewhere [50, 51]. Dissection of the in vivo function of noggin and/or TGF- β is an ongoing area of research.…”

“…iPS cells derived from patients or iPS cells engineered with a disease gene are differentiated into myocytes and are now being used to model diseases in vitro [52]. At present, only channelopathies, such as LQTS-type 2 [53] and LQTS-type 3 [54], have been well studied because of the comparatively easy functional analysis needed for characterization [51]. However, more complicated diseases will require culture methods that more closely model the native tissue environment.…”

Molecular Analysis of Long-Term Cultured Cardiac Stem Cells for Cardiac Regeneration

“…The results suggested that these CSCs retained multiple developmental potential to some extent. Consequently, we investigated these CSCs in detail, hoping to establish the regeneration method by using c-Kit-positive cardiac cells [1][2][3][4][5][6][7][8][9][10][11][12].…”