scholarly journals Epigenetic Regulation of Mesenchymal Stem Cells: A Focus on Osteogenic and Adipogenic Differentiation

2011 ◽  
Vol 2011 ◽  
pp. 1-18 ◽  
Author(s):  
Chad M. Teven ◽  
Xing Liu ◽  
Ning Hu ◽  
Ni Tang ◽  
Stephanie H. Kim ◽  
...  

Stem cells are characterized by their capability to self-renew and terminally differentiate into multiple cell types. Somatic or adult stem cells have a finite self-renewal capacity and are lineage-restricted. The use of adult stem cells for therapeutic purposes has been a topic of recent interest given the ethical considerations associated with embryonic stem (ES) cells. Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Owing to their ease of isolation and unique characteristics, MSCs have been widely regarded as potential candidates for tissue engineering and repair. While various signaling molecules important to MSC differentiation have been identified, our complete understanding of this process is lacking. Recent investigations focused on the role of epigenetic regulation in lineage-specific differentiation of MSCs have shown that unique patterns of DNA methylation and histone modifications play an important role in the induction of MSC differentiation toward specific lineages. Nevertheless, MSC epigenetic profiles reflect a more restricted differentiation potential as compared to ES cells. Here we review the effect of epigenetic modifications on MSC multipotency and differentiation, with a focus on osteogenic and adipogenic differentiation. We also highlight clinical applications of MSC epigenetics and nuclear reprogramming.

Author(s):  
Vikash Chandra ◽  
Pratheesh Mankuzhy ◽  
Taru Sharma G.

Background: The consistent, self-renewal capability and wide-ranging differentiation potential during specific physiologic conditions mark stem cells as a novel candidate not only for biomedical research and regenerative therapy but also as an alternative source in research related to life sciences. This vital and distinct characteristic of stem cells, enable them to offer unprecedented hope in treating many diseases and disorders, which are otherwise difficult to treat. Several efforts are still being undertaken to enhance the efficiency of MSCs for better therapeutic applications. Objective: In recent past several studies have been conducted regarding isolation of stem cells from diverse sources and are being used clinically in veterinary regenerative therapy. But till date only a few systemic studies are available. This study provides a comprehensive analysis of the findings from basic and applied research conducted in stem cell therapeutics with particular emphasis on animals. Result: On the basis of their sources, stem cells can be classified as adult or embryonic stem (ES) cells. Physiologically, the ES cells have capability to differentiate into all body cells and develop into normal adult organism; whereas, adult stem cells serve as repair system by restoring damaged tissues of the body. The adult stem cells referred as Mesenchymal stem cells (MSCs) can be derived from various adult body organs whereas embryos give rise to embryonic stem cells. MSCs, passes unique property of proliferation, trans-differentiation and secretion of important biomolecules to create microenvironment; which is immunosuppressive and stimulate native MSCs of damaged tissue. MSCs being immunocompromised cells can be used in autologous as well as in allogenic mode. Conclusion: In Veterinary therapeutics, MSCs equipped with engineering and pharmaceutical modifications offer a potentially candidate in the treatment of wound healing, nerve injury, bone/ligament injury etc. and also bear a great hope in improvement of udder health and milk production in animals.


2021 ◽  
Author(s):  
Kannan Govindaraj ◽  
Sakshi Khurana ◽  
Marcel Karperien ◽  
Janine Nicole Post

The master transcription factor SOX9 is a key player during chondrocyte differentiation, cartilage development, homeostasis and disease. Modulation of SOX9 and its target gene expression is essential during chondrogenic, osteogenic and adipogenic differentiation of human mesenchymal stem cells (hMSCs). However, lack of sufficient knowledge about the signaling interplay during differentiation remains one of the main reasons preventing successful application of hMSCs in regenerative medicine. We previously showed that Transcription Factor - Fluorescence Recovery After Photobleaching (TF-FRAP) can be used to study SOX9 dynamics at the single cell level. We showed that changes in SOX9 dynamics are linked to its transcriptional activity. Here, we investigated SOX9 dynamics during differentiation of hMSCs into the chondrogenic, osteogenic and adipogenic lineages. We show that there are clusters of cells in hMSCs with distinct SOX9 dynamics, indicating that there are a number of subpopulations present in the heterogeneous hMSCs. SOX9 dynamics data at the single cell resolution revealed novel insights about its activity in these subpopulations (cell types). In addition, the response of SOX9 to differentiation stimuli varied in these subpopulations. Moreover, we identified donor specific differences in the number of cells per cluster in undifferentiated hMSCs, and this correlated to their differentiation potential.


2009 ◽  
Vol 18 (5-6) ◽  
pp. 581-590 ◽  
Author(s):  
Koichi Oishi ◽  
Hirofumi Noguchi ◽  
Hiroshi Yukawa ◽  
Shuji Hayashi

Somatic stem cells can be isolated from a variety of sources. Although some studies have suggested that somatic stem cells may represent a cell population that is very similar to embryonic stem (ES) cells, it remains unclear whether somatic stem cells retain the potential to differentiate into any cell type derived from the three germ layers. In this study, we investigated the transdifferentiation potential of somatic stem cells using adipose tissue-derived stem/progenitor cells (ASCs; mesodermal stem cells) and pancreatic stem cells (endodermal stem cells). Previous reports from other groups describe the protocol that has been used to differentiate ASCs or mesenchymal stem cells (MSCs) in bone marrow into insulin-producing cells. Induction 1: ASCs were cultured for 3 days in ultra-low attachment plates under serum-free conditions. Induction 2: ASCs were cultured for 24 h with L-DMEM, and reinduced with serum-free H-DMEM for another 10 h. Unlike previous reports, we did not get ASCs to express any pancreas-specific genes, including insulin-1 or insulin-2. Pancreatic stem cells were induced to differentiate into adipo/osteogenic by the following protocols. Induction protocol 1: ACSs were cultured for 7 days with medium containing indometacin, dexamethasone, hydrocortisone, and insulin for adipogenic differentiation. Induction protocol 2: The cells were cultured for 7 days with medium containing dexamethasone, ascorbate-2-phosphate, and β-glycerophosphate for osteogenic differentiation. Although these approaches have been widely used for adipo/osteogenic differentiation from MSCs, adipo/osteogenic differentiation from pancreatic stem cells was not observed. These data suggest that it is not easy for somatic stem cells to transdifferentiate into other germ cell types, at least, under these conditions.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ivana Catacchio ◽  
Simona Berardi ◽  
Antonia Reale ◽  
Annunziata De Luisi ◽  
Vito Racanelli ◽  
...  

In contrast to the pluripotentembryonic stem cells(ESCs) which are able to give rise to all cell types of the body, mammalianadult stem cells(ASCs) appeared to be more limited in their differentiation potential and to be committed to their tissue of origin. Recently, surprising new findings have contradicted central dogmas of commitment of ASCs by showing their plasticity to differentiate across tissue lineage boundaries, irrespective of classical germ layer designations. The present paper supports the plasticity of thebone marrow stem cells(BMSCs), bringing the most striking and the latest evidences of the transdifferentiation properties of thebone marrow hematopoietic and mesenchymal stem cells(BMHSCs, and BMMSCs), the two BM populations of ASCs better characterized. In addition, we report the possible mechanisms that may explain these events, outlining the clinical importance of these phenomena and the relative problems.


2021 ◽  
Vol 2 ◽  
pp. 2
Author(s):  
Vikash Chandra ◽  
Mudasir Bashir Gugjoo ◽  
Amarpal ◽  
G. Taru Sharma

Stem cells are wonder cells that function silently in an individual to grow and/to regenerate. There are various stem cell types; some especially embryonic stem cells (ESCs) favor individual development while more advanced cells like adult stem cells play mostly repair and tissue matrix secretion role. Among various adult stem cell types, mesenchymal stem cells play an important role to maintain tissue homeostasis. These cells are available in almost all the tissue types and exhibit features similar to the ESCs. These cells are immunoevasive, immune modulatory, and/anti-inflammatory, and bear properties of self-renewal (although limited), multiplication, and differentiation. In addition, these cells are able to migrate and home-in to the distant tissues. All these features make these cells potential candidates for therapeutic applications and drug development. There are various studies that have favored their role in therapeutics and drug development, although more studies and further insights are desired to make stem cell therapy a definitive therapeutic option.


2021 ◽  
pp. 19-21
Author(s):  
Pradeep Kumar Radhakrishnan ◽  
Roshini Ambat ◽  
Sushamma Vikraman ◽  
Geetha Nagasree N ◽  
Hariharan Hariharan ◽  
...  

Mesenchymal stem cells (MSCs) are multipotent adult stem cells widely distributed in the bone marrow, umbilical cord, fat, and other tissues and have high proliferation, multi-differentiation, and immunoregulatory abilities. They can inhibit the proliferation of immune cells and the secretion of inammatory factors [26]. Compared with MSCs from other sources, human umbilical cord MSCs (hUCMSCs) have many advantages, such as a wide source, easy access to materials, strong proliferation ability, low immunogenicity, and great differentiation potential. They are most likely to become pluripotent stem cells with clinical application prospects. Wharton's jelly mesenchymal stem cells – WJMSC- provide three classic advantages – ease of collection with no legal or ethical issues, high differentiating potential and low immunogenicity. Shorter doubling time (21) and an extensive ex vivo expansion capacity provides yet another privileged status to these cells compared with embryonic stem cells. Therapeutic potential of these cells lie in their immuno-modulatory properties involving both innate and adaptive immunity. Graft vs Host disease (GvHD), Post transplant scenarios and autoimmune disorders could witness a revolution in treatment approach with greater understanding of the mechanism action of these cells. Regenerative medicine should get an immense benet from proper understanding and utilization of these cells.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Elham Zomorodian ◽  
Mohamadreza Baghaban Eslaminejad

While small bone defects heal spontaneously, large bone defects need surgical intervention for bone transplantation. Autologous bone grafts are the best and safest strategy for bone repair. An alternative method is to use allogenic bone graft. Both methods have limitations, particularly when bone defects are of a critical size. In these cases, bone constructs created by tissue engineering technologies are of utmost importance. Cells are one main component in the manufacture of bone construct. A few cell types, including embryonic stem cells (ESCs), adult osteoblast, and adult stem cells, can be used for this purpose. Mesenchymal stem cells (MSCs), as adult stem cells, possess characteristics that make them good candidate for bone repair. This paper discusses different aspects of MSCs that render them an appropriate cell type for clinical use to promote bone regeneration.


Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.


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