Browsing by Subject "differentiation"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item Adipose Tissue-Derived Mesenchymal Stem Cells(MDPI, 2021-12-06) Bunnell, Bruce A.The long-held belief about adipose tissue was that it was relatively inert in terms of biological activity. It was believed that its primary role was energy storage; however, that was shattered with the discovery of adipokines. Scientists interested in regenerative medicine then reported that adipose tissue is rich in adult stromal/stem cells. Following these initial reports, adipose stem cells (ASCs) rapidly garnered interest for use as potential cellular therapies. The primary advantages of ASCs compared to other mesenchymal stem cells (MSCs) include the abundance of the tissue source for isolation, the ease of methodologies for tissue collection and cell isolation, and their therapeutic potential. Studies conducted both in vitro and in vivo have demonstrated that ASCs are multipotent, possessing the ability to differentiate into cells of mesodermal origins, including adipocytes, chondrocytes, osteoblast and others. Moreover, ASCs produce a broad array of cytokines, growth factors, nucleic acids (miRNAs), and other macromolecules into the surrounding milieu by secretion or in the context of microvesicles. The secretome of ASCs has been shown to alter tissue biology, stimulate tissue-resident stem cells, change immune cell activity, and mediate therapeutic outcomes. The quality of ASCs is subject to donor-to-donor variation driven by age, body mass index, disease status and possibly gender and ethnicity. This review discusses adipose stromal/stem cell action mechanisms and their potential utility as cellular therapeutics.Item Molecular Regulation of Cardiac Stem Cell Growth and Differentiation by Extrinsic Factors and Novel Intracellular Signaling Pathways(2008-05-01) Bartosh, T.J.; Rouel S. Roque; Harold Sheedlo; Robert WordingerT. J. Bartosh, Molecular regulation of cardiac stem cell growth and differentiation by extrinsic factors and novel intracellular signaling pathways. Doctors of Philosophy (Biomedical Sciences), May 2008, 293 pp., 4 tables, 59 illustrations, bibliography, 353 titles. Insufficient myocardial regeneration following ischemic injury provokes cardiac dysfunction, adverse tissue remodeling, and ultimately heart failure. Stem cell replacement therapy appears to be a promising strategy for improving cardiac function, however, challenges involving inadequate stem cell differentiation, engraftment, and survival following transplantation currently impede the efficacy of regeneration protocols. These limitations emphasize the significance of identifying extrinsic factors and corresponding molecular mechanisms regulating cardiac cell differentiation. Recent reports recognizing a stem cell component in the adult heart (i.e. cardiac stem cells, CSC) have provided additional targets and/or tools for myocardial repair. This investigation verified the presence of CSC in the adult dog heart, described methods to generate three dimensional (3D) cardiac microtissues (‘cardiospheres’) from CSC, and revealed features of cardiospheres potentially useful for identifying extrinsic procardiogenic factors, evaluating myocardial response to stress, and delivering functional CSC into the damaged heart. Specifically, cardiosphere formation was facilitated by culturing CSC in growth medium on a poly-L-ornithine substratum. Cardiospheres are comprised of interior cells that exhibited characteristics of CSC; differentiating cardiomyocytes at the periphery with organized contractile machinery; and/or vascular cells capable of forming vessel-like networks. Upon co-culture with neonatal cardiomycocytes, spheres developed foci of contracting regions. Furthermore, cardiospheres exhibited increased resistance to oxidative stress and survived subcutaneous injections without undergoing neoplastic transformation further supporting their ability to effectively promote myocardial regeneration. Retionic acid (RA), the active form of vitamin A, augmented expression of myocyte-specific proteins in cardiospheres, thus, RA may improve the success of cardiac regenerative therapies and provide an appropriate stimulus to model underlying mechanisms fundamental for CSC differentiation. The tendency for cultured stem cells to undergo various levels of multi-lineage commitment is, however, cumbersome for deciphering precise cues that direct cell fate decisions. In this study, the molecular pathways important for RA-induced cardiac differentiation were examined using h9c2 cardioblasts as a stable cell model. In h9c2 cells, RA treatment promoted transcriptional enhancement of the muscle-enriched gene regulatory protein MEF2C, morphological alterations indicative of differentiation, and a robust increase in expression of myocyte differentiation genes including cardiac myosin heavy chain (cMHC) and ventricular myosin light chain-2 (vMLC2). These changes were preceded by rapid events involving elevation of intracellular Ca^2+ and phosphorylation of p38 MAPK. The effects of RA were attenuated using CA^2+ buffering agents or chemical inhibitors of L-type Ca^2+ channels (LTCC) and the phosphatase calcinuerin, but not by RA receptor antagonists. Furthermore, overexpression of dominant negative (dn) MEF2C, dnp38 MAPK, or CAIN, a physiological calcineruin inhibitor, abrogated MEF2 activity and RA-induced differentiation. These results imply that RA promotes cardiomyocyte differentiation, independent of RA response element activation, via induction of CA^2+ -regulated signaling pathways by activating the LTCC-calcineurin/38MAPK-MEF2 axis. Taken together, these findings enhance our understanding of extrinsic factors and molecular mechanisms indispensable for myocyte differentiation and subsequently provide novel therapeutic targets and cellular tools for regeneration and repair of damaged myocardium.Item The Enigmatic Protein Kinase C-eta(MDPI, 2019-02-13) Basu, AlakanandaProtein kinase C (PKC), a multi-gene family, plays critical roles in signal transduction and cell regulation. Protein kinase C-eta (PKCeta) is a unique member of the PKC family since its regulation is distinct from other PKC isozymes. PKCeta was shown to regulate cell proliferation, differentiation and cell death. It was also shown to contribute to chemoresistance in several cancers. PKCeta has been associated with several cancers, including renal cell carcinoma, glioblastoma, breast cancer, non-small cell lung cancer, and acute myeloid leukemia. However, mice lacking PKCeta were more susceptible to tumor formation in a two-stage carcinogenesis model, and it is downregulated in hepatocellular carcinoma. Thus, the role of PKCeta in cancer remains controversial. The purpose of this review article is to discuss how PKCeta regulates various cellular processes that may contribute to its contrasting roles in cancer.