Mesenchymal Stem Cells Obtained from Synovial Fluid Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells on a Matrigel Coating Exhibited Enhanced Proliferation and Differentiation Potential

Hereditary hemorrhagic telangiectasia is a rare disease with autosomal dominant inheritance. More than 80% hereditary hemorrhagic telangiectasia patients carry heterozygous mutations of Endoglin or Activin receptor-like kinase-1 genes. Endoglin plays important roles in vasculogenesis and human vascular disease. In this report, we found a novel missense mutation (c.88T > C) of Endoglin gene in a hereditary hemorrhagic telangiectasia 1 patient. Induced pluripotent stem cells of the patient were generated and differentiated into endothelial cells. The hereditary hemorrhagic telangiectasia-induced pluripotent stem cells have reduced differentiation potential toward vascular endothelial cells and defective angiogenesis with impaired tube formation. Endoplasmic reticulum retention of the mutant Endoglin (Cys30Arg, C30R) causes less functional protein trafficking to cell surface, which contributes to the pathogenesis of hereditary hemorrhagic telangiectasia. Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 genetic correction of the c.88T > C mutation in induced pluripotent stem cells revealed that C30R mutation of Endoglin affects bone morphogenetic protein 9 downstream signaling. By establishing a human induced pluripotent stem cell from hereditary hemorrhagic telangiectasia patient peripheral blood mononuclear cells and autologous correction on mutant hereditary hemorrhagic telangiectasia-induced pluripotent stem cells, we were able to identify a new disease-causing mutation, which facilitates us to understand the roles of Endoglin in vascular development and pathogenesis of related vascular diseases.

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Human Amniotic Mesenchymal Stem Cell-Derived Induced Pluripotent Stem Cells May Generate a Universal Source of Cardiac Cells

Stem Cells and Development ◽

10.1089/scd.2011.0435 ◽

2012 ◽

Vol 21 (15) ◽

pp. 2798-2808 ◽

Cited By ~ 26

Author(s):

Xiaohu Ge ◽

I-Ning E. Wang ◽

Ildiko Toma ◽

Vittorio Sebastiano ◽

Jianwei Liu ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Cardiac Cells ◽

Induced Pluripotent

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HIF-1α Affects the Neural Stem Cell Differentiation of Human Induced Pluripotent Stem Cells via MFN2-Mediated Wnt/β-Catenin Signaling

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.671704 ◽

2021 ◽

Vol 9 ◽

Author(s):

Peng Cui ◽

Ping Zhang ◽

Lin Yuan ◽

Li Wang ◽

Xin Guo ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Induced Pluripotent Stem Cells ◽

Neural Stem Cell ◽

Pluripotent Stem Cells ◽

Stem Cell Differentiation ◽

Differentiation Potential ◽

Developmental Potential ◽

Induced Pluripotent

Hypoxia-inducible factor 1α (HIF-1α) plays pivotal roles in maintaining pluripotency, and the developmental potential of pluripotent stem cells (PSCs). However, the mechanisms underlying HIF-1α regulation of neural stem cell (NSC) differentiation of human induced pluripotent stem cells (hiPSCs) remains unclear. In this study, we demonstrated that HIF-1α knockdown significantly inhibits the pluripotency and self-renewal potential of hiPSCs. We further uncovered that the disruption of HIF-1α promotes the NSC differentiation and development potential in vitro and in vivo. Mechanistically, HIF-1α knockdown significantly enhances mitofusin2 (MFN2)-mediated Wnt/β-catenin signaling, and excessive mitochondrial fusion could also promote the NSC differentiation potential of hiPSCs via activating the β-catenin signaling. Additionally, MFN2 significantly reverses the effects of HIF-1α overexpression on the NSC differentiation potential and β-catenin activity of hiPSCs. Furthermore, Wnt/β-catenin signaling inhibition could also reverse the effects of HIF-1α knockdown on the NSC differentiation potential of hiPSCs. This study provided a novel strategy for improving the directed differentiation efficiency of functional NSCs. These findings are important for the development of potential clinical interventions for neurological diseases caused by metabolic disorders.

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Correction: Efficient Commitment to Functional CD34+ Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem Cells

PLoS ONE ◽

10.1371/annotation/ebddb7ce-712c-4f9d-8412-20dc827c30b9 ◽

2012 ◽

Vol 7 (8) ◽

Author(s):

Yulin Xu ◽

Lizhen Liu ◽

Lifei Zhang ◽

Shan Fu ◽

Yongxian Hu ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Induced Pluripotent Stem Cells ◽

Progenitor Cells ◽

Pluripotent Stem Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Induced Pluripotent

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Stem Cells - biological update and cell therapy progress

Medicine and Pharmacy Reports ◽

10.15386/cjmed-483 ◽

2015 ◽

Vol 88 (3) ◽

pp. 265-271 ◽

Cited By ~ 16

Author(s):

Mihai Girlovanu ◽

Sergiu Susman ◽

Olga Soritau ◽

Dan Rus-Ciuca ◽

Carmen Melincovici ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Therapy ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Molecular Mechanisms ◽

Embryonic Stem ◽

Type I ◽

Differentiation Potential ◽

Induced Pluripotent

In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected.Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs).Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research.The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases.Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues.This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine.

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