scholarly journals Connexin43 is Dispensable for Early Stage Human Mesenchymal Stem Cell Adipogenic Differentiation But is Protective against Cell Senescence

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 474 ◽  
Author(s):  
Qing Shao ◽  
Jessica L. Esseltine ◽  
Tao Huang ◽  
Nicole Novielli-Kuntz ◽  
Jamie E. Ching ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Gap Junctional Intercellular Communication ◽  
Cx43 Expression ◽  
Junction Protein

In the last couple of decades, there has been a growing optimism surrounding the potential transformative use of human mesenchymal stem cells (MSCs) and human-induced pluripotent stem cells (iPSCs) for regenerative medicine and disease treatment. In order for this to occur, it is first essential to understand the mechanisms underpinning their cell-fate specification, which includes cell signaling via gap junctional intercellular communication. Here, we investigated the role of the prototypical gap junction protein, connexin43 (Cx43), in governing the differentiation of iPSCs into MSCs and MSC differentiation along the adipogenic lineage. We found that control iPSCs, as well as iPSCs derived from oculodentodigital dysplasia patient fibroblasts harboring a GJA1 (Cx43) gene mutation, successfully and efficiently differentiated into LipidTox and perilipin-positive cells, indicating cell differentiation along the adipogenic lineage. Furthermore, the complete CRISPR-Cas9 ablation of Cx43 from iPSCs did not prevent their differentiation into bona fide MSCs or pre-adipocytes, strongly suggesting that even though Cx43 expression is upregulated during adipogenesis, it is expendable. Interestingly, late passage Cx43-ablated MSCs senesced more quickly than control cells, resulting in failure to properly differentiate in vitro. We conclude that despite being upregulated during adipogenesis, Cx43 plays no detectable role in the early stages of human iPSC-derived MSC adipogenic differentiation. However, Cx43 may play a more impactful role in protecting MSCs from premature senescence.

scholarly journals Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Taeui Hong ◽  
Moon Young Kim ◽  
Dat Da Ly ◽  
Su Jung Park ◽  
Young Woo Eom ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Mitochondrial Biogenesis ◽  
Biological Activities ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Fate ◽  
Mitochondrial Functions

Abstract Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.

scholarly journals Co-expression of MDM2 and CDK4 in transformed human mesenchymal stem cells induces dedifferentiated liposarcoma potency

2018 ◽  
Author(s):  
Yu Jin Kim ◽  
Minjung Sung ◽  
Dan Bi Yu ◽  
Mingi Kim ◽  
Ji-Young Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Growth ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Dedifferentiated Liposarcoma ◽  
Cell Growth And Migration ◽  
Well Differentiated ◽  
And Migration

AbstractAmplification and overexpression of MDM2 and CDK4 are well-known diagnostic criteria of well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS). Although it was reported that depletion of MDM2 or CDK4 decreased proliferation in DDLPS cell lines, it remains unclear whether MDM2 and CDK4 induce WDLPS/DDLPS tumorigenesis. We examined whether MDM2 and/or CDK4 produce WDLPS/DDLPS using transformed human bone marrow stem cells (BMSCs), 2H and 5H, with five oncogenic hits (overexpression of hTERT, TP53 degradation, RB inactivation, c-MYC stabilization, and overexpression of HRASv12). In vitro functional experiments revealed that co-overexpression of MDM2 and CDK4 plays key roles in tumorigenesis by increasing cell growth and migration and inhibiting adipogenic differentiation potency compared to sole expression of MDM2 or CDK4. Using mouse xenograft models, we found that co-overexpression of MDM2 and CDK4 in 5H cells with five additional oncogenic mutations can develop proliferative DDLPS in vivo. Our results suggest that co-overexpression of MDM2 and CDK4 induces DDLPS tumour potency in transformed human BMSCs by accelerating cell growth and migration and blocking adipogenetic potential incooperation with multiple genetic factors.

In Vitro Effect of 30 nm Silver Nanoparticles on Adipogenic Differentiation of Human Mesenchymal Stem Cells

2016 ◽  
Vol 12 (3) ◽  
pp. 525-535 ◽  
Author(s):  
Wei He ◽  
Arne Kienzle ◽  
Xujie Liu ◽  
Werner E. G. Müller ◽  
Tarek A. Elkhooly ◽  
...  
Keyword(s):  
Stem Cells ◽  
Silver Nanoparticles ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells

scholarly journals Ca2+-activated mitochondrial biogenesis and functions improve stem cell fate in Rg3-treated human mesenchymal stem cells

2020 ◽  
Author(s):  
Taeui Hong ◽  
Moon Young Kim ◽  
Dat Da Ly ◽  
Su Jung Park ◽  
Young Woo Eom ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Mitochondrial Biogenesis ◽  
Biological Activities ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Fate ◽  
Mitochondrial Functions

Abstract Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.

scholarly journals Ca2+-Activated Mitochondrial Biogenesis and Functions Improve Stem Cell Fate in Rg3-Treated Human Mesenchymal Stem Cells

2020 ◽  
Author(s):  
Taeui Hong ◽  
Moon Young Kim ◽  
Dat Da Ly ◽  
Su Jung Park ◽  
Young Woo Eom ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Mitochondrial Biogenesis ◽  
Biological Activities ◽  
Adipogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Stem Cell Fate ◽  
Mitochondrial Functions

Abstract Although mitochondrial functions are essential for cell survival, their critical roles in stem cell fate, including proliferation, differentiation, and senescence, remain elusive. Ginsenoside Rg3 exhibits various biological activities and reportedly increases mitochondrial biogenesis and respiration. Herein, we observed that Rg3 increased proliferation and suppressed senescence of human bone marrow-derived mesenchymal stem cells. Osteogenic, but not adipogenic, differentiation was facilitated by Rg3 treatment. Rg3 suppressed reactive oxygen species production and upregulated mitochondrial biogenesis and antioxidant enzymes, including superoxide dismutase. Consistently, Rg3 strongly augmented basal and ATP synthesis-linked respiration with high spare respiratory capacity. Rg3 treatment elevated cytosolic Ca2+ concentration contributing to mitochondrial activation. Reduction of intracellular or extracellular Ca2+ levels strongly inhibited Rg3-induced activation of mitochondrial respiration and biogenesis. Taken together, Rg3 enhances capabilities of mitochondrial and antioxidant functions mainly through a Ca2+-dependent pathway, which improves the proliferation and differentiation potentials and prevents the senescence of human mesenchymal stem cells.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

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.

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