Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells

Abstract

Abstract-Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. Key Words: cardiomyocytes Ⅲ adipose tissue Ⅲ differentiation Ⅲ stem cells Ⅲ cell therapy C ardiomyocyte differentiation mainly takes place during neonatal and perinatal life. In adult life, the regenerative potential of cardiac tissue is limited and is not sufficient to prevent from the degeneration occurring in pathological conditions such as myocardial infarction. 1 Cell transplantation seems to be an alternative to overcome this problem. 2 This led to numerous investigations to identify a putative source of transplanted cells and to better understand cardiomyocyte proliferation and differentiation in order to drive the fate of stem cells toward this process. Different sources, ie, embryonic, fetal, and adult cells have been investigated and tested. 3-8 Among them, mesenchymal stem cells (MSCs) isolated from bone marrow are accepted to give rise to connective tissue cell types. Their differentiation toward cardiomyocyte was obtained in vitro and in vivo. However, immortalized MSCs and treatment with the DNA demethylation agent 5-azacytidine was necessary to reveal their cardiogenic potential in vitro. 6 Adipose tissues are mesodermic tissues, which develop during perinatal and postnatal life. 9 They are strongly involved in various metabolic disorders such as obesity. Tremendous changes in adipose mass are achieved through highly controlled processes such as angiogenesis, precursor recruitment, proliferation, differentiation, dedifferentiation, and apoptosis as well. More recently, differentiation of cells derived or purified from adipose tissue toward phenotypes different from adipocyte was described. 10 -13 However, the characterization of cells with such potential remains to be done. The present statement is that adipose tissue consists of mature adipocytes and the stroma vascular fraction (SVF). SVF is a heterogeneous cell population. Among them the identified ones are vascular cells (endothelial, smooth muscle cell, circulating blood cells) and an undefined fibroblast-like cell population recently described as a multipotential stem cell population for various mesodermic lineage. 10 -13 This led us to test the in vitro cardiomyogenic potential of cells purified from adipose tissue. In the results reported in this study, adipose-derived cells (SVF cells) from primary culture spontaneously differentiate into cells with morphological, molecular, and functional properties of cardiomyocytes. Materials and Methods AnimalsSix-week-old adult male C57Bl/6N mice (Harlan, France) were housed in conventional animal quarters (SPS barrier facility). Mice were killed by cervical dislocation under CO 2 anesthesia. All procedures were performed according to SELASA norms.

In vitro cardiomyogenic differentiation of adipose‐derived stromal cells using transforming growth factor‐β1

“…15,27,[31][32][33] Contracting cells with CMC features were seen during adipose stromal cell culture due to spontaneous differentiation, but the frequency was very low (0.02-0.07%). 7 The present study demonstrates that TGF-b1 promotes ADSC cardiomyogenic differentiation in vitro. The differentiated cells expressed troponin I, cardiac MHC, and a-sarcomeric actin (Figures 2-5).…”

“…Embryonic stem cells, 1 bone marrow-derived mesenchymal stem cells (BMMSCs), [2][3][4][5] umbilical cord blood cells, 6 and adipose-derived stromal cells (ADSCs) 7,8 can differentiate into cardiomyocytes (CMCs). Autologous BMMSCs have been the most investigated in clinical studies to treat ischemic myocardium.…”

Endothelial cells guided by immobilized gradients of vascular endothelial growth factor on porous collagen scaffolds

“…Some of the extensively investigated cell types include bone marrow-derives adult stem cells [7,8] and embryonic stem cells [9][10][11]. Some of the other cell types that carry some doubts in terms of their capability for the purpose of myocardial regeneration are the adipose-derived adult stem cells [12,13] and the adult skeletal myoblasts [14]. Two recently explored area of cell source are the resident cardiac progenitor cells and induced pluripotent stem cells (iPS).…”

Perspectivas futuras de tratamiento en la insuficiencia cardíaca: del trasplante de células a la regeneración cardíaca

“…Las células mesenquimales se pueden obtener a partir de varios tejidos, principalmente médula ósea y tejido graso (también conocido como fracción de estroma vascular). Las cé-lulas mesenquimales, tanto de la grasa como de la mé-dula ósea, han demostrado su capacidad para diferenciarse in vitro en células de músculo cardíaco y, a la vez, en células endoteliales, haciéndolas especialmente atractivas no sólo por que pueden regenerar el miocardio, sino por que contribuyen a la neoangiogénesis y vasculogénesis [42][43][44] . En modelos experimentales de infarto de miocardio en rata y en cerdo, se han empleado células mesenquimales de médula ósea que demostraron su capacidad de mejorar la función cardíaca 45 y diferenciarse en células musculares cardíacas 46 .…”