TGF-β1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro

Abstract

The adult mammalian heart has limited regenerative capacity and was generally considered to contain no dividing cells. Recently, however, a resident population of progenitor cells has been identified, which could represent a new source of cardiomyocytes. Here, we describe the efficient isolation and propagation of human cardiomyocyte progenitor cells (hCMPCs) from fetal heart and patient biopsies. Establishment of hCMPC cultures was remarkably reproducible, with over 70% of adult atrial biopsies resulting in robustly expanding cell populations. Following the addition of transforming growth factor beta, almost all cells differentiated into spontaneously beating myocytes with characteristic cross striations. hCMPC-derived cardiomyocytes showed gap-junctional communication and action potentials of maturing cardiomyocytes. These are the first cells isolated from human heart that proliferate and form functional cardiomyocytes without requiring coculture with neonatal myocytes. Their scalability and homogeneity are unique and provide an excellent basis for developing physiological, pharmacological, and toxicological assays on human heart cells in vitro.

Human Cardiac Progenitor Cell Grafts as Unrestricted Source of Supernumerary Cardiac Cells in Healthy Murine Hearts

“…This could imply that c-kit pos and Sca-1 pos progenitor cells, so far considered rather different cell population with overlapping figures [27] could represent two phenotypic stages of the same original population, in which c-kit expression could mark the more immature, slowly dividing progenitor cell pool, identified also in niches in vivo [20], while a more mature, actively growing and potentially cardiogenic progenitor cell population (a transit-amplifying population?) can be identified by the Sca-1 expression, as already demonstrated both in vitro and in vivo [13,14,25,28]. The hCPC phenotype was homogeneous in all preparations from the 13 donor cardiac patients and stable also in long-term conventional cultures (Sca-1 pos cells are able to uphold their phenotype for more than 50 passages).…”

“…Concerning myocardium, muscle and nonmuscle cell population from multipotent progenitors located in the first and second heart fields contribute to cardiogenesis [9,10], tangling the identification of the resident progenitor cells actually involved in myocardial homeostasis throughout lifetime [11]. Cells expressing c-kit/CD117 have been acknowledged as the ''true cardiomyocyte progenitors'' [12]; however, Sca-1 has been recently shown to be a marker identifying a murine [13] and a human [14] heart cell population with cardiomyogenic potential, since both could generate new cardiomyocytes in vitro and in vivo on specific treatments [13][14][15][16]. Indeed, Sca-1 is a very efficient marker to isolate and to enrich for progenitor cells from various tissues [2,17] and has been associated with multipotency and self-renewal in bone marrow, skeletal muscle, dermis, heart, and liver [18].…”

Newt cells secrete extracellular vesicles with therapeutic bioactivity in mammalian cardiomyocytes

“…Activation of the PI3K/AKT pathway, which is known to promote both cardiomyocyte proliferation and survival (Figure 3(a)) [38], peaked at 12 h and subsided 24 h after A1-CM exposure (Figure 3(b)). Conversely, there was a significant reduction in the expression of genes associated with cellular differentiation, including bone morphogenetic protein (BMP) signalling ( Z  = −1.13) and TGF-β signalling ( Z  = −1.89) pathways [39]. Also shown are the p -values for each of the identified signalling pathways as well as the ratio of genes significantly up- or down-regulated relative to all genes associated with that pathway.…”

The difference between ballistocardiography and stem cells

“…So let us focus on the horizon, forget the obstacles and enjoy the hype for as long as it lasts. [2][3][4][5][6][7][8] One of the key issues with respect to the stem cell confusion is the terminology. Therefore, the work by Qian et al is important as they try to provide some insight into the various kinds of endothelial progenitor cells (EPCs).…”

“…Our work on cardiomyocyte progenitor cells proved the opposite, showing there are different progenitor cells in the heart compared with bone marrow. 7,8 Whether the niche is crucial to keep the cells undifferentiated or decide fate in pathological circumstances is still unclear.…”