scholarly journals Tolloid‐Like 1 Negatively Regulates Hepatic Differentiation of Human Induced Pluripotent Stem Cells Through Transforming Growth Factor Beta Signaling

2020 ◽  
Vol 4 (2) ◽  
pp. 255-267
Author(s):  
Ayumi Kiso ◽  
Yukiko Toba ◽  
Susumu Tsutsumi ◽  
Sayaka Deguchi ◽  
Keisuke Igai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Induced Pluripotent Stem Cells ◽  
Transforming Growth Factor Beta ◽  
Pluripotent Stem Cells ◽  
Transforming Growth Factor ◽  
Hepatic Differentiation ◽  
Growth Factor Beta ◽  
Induced Pluripotent

scholarly journals Stage-Specific Role of Amelx Activation in Stepwise Ameloblast Induction from Mouse Induced Pluripotent Stem Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 7195
Author(s):  
Xinchao Miao ◽  
Kunimichi Niibe ◽  
Maolin Zhang ◽  
Zeni Liu ◽  
Praphawi Nattasit ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Induced Pluripotent Stem Cells ◽  
Transcriptional Activation ◽  
Pluripotent Stem Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Calcium Deposition ◽  
Surface Ectoderm ◽  
Induced Pluripotent

Amelogenin comprises ~90% of enamel proteins; however, the involvement of Amelx transcriptional activation in regulating ameloblast differentiation from induced pluripotent stem cells (iPSCs) remains unknown. In this study, we generated doxycycline-inducible Amelx-expressing mouse iPSCs (Amelx-iPSCs). We then established a three-stage ameloblast induction strategy from Amelx-iPSCs, including induction of surface ectoderm (stage 1), dental epithelial cells (DECs; stage 2), and ameloblast lineage (stage 3) in sequence, by manipulating several signaling molecules. We found that adjunctive use of lithium chloride (LiCl) in addition to bone morphogenetic protein 4 and retinoic acid promoted concentration-dependent differentiation of DECs. The resulting cells had a cobblestone appearance and keratin14 positivity. Attenuation of LiCl at stage 3 together with transforming growth factor β1 and epidermal growth factor resulted in an ameloblast lineage with elongated cell morphology, positivity for ameloblast markers, and calcium deposition. Although stage-specific activation of Amelx did not produce noticeable phenotypic changes in ameloblast differentiation, Amelx activation at stage 3 significantly enhanced cell adhesion as well as decreased proliferation and migration. These results suggest that the combination of inducible Amelx transcription and stage-specific ameloblast induction for iPSCs represents a powerful tool to highlight underlying mechanisms in ameloblast differentiation and function in association with Amelx expression.

scholarly journals Chondrogenic Differentiation from Induced Pluripotent Stem Cells Using Non-Viral Minicircle Vectors

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 582 ◽  
Author(s):  
Yeri Alice Rim ◽  
Yoojun Nam ◽  
Narae Park ◽  
Hyerin Jung ◽  
Kijun Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Transforming Growth Factor Beta ◽  
Pluripotent Stem Cells ◽  
Transforming Growth Factor ◽  
Cartilage Regeneration ◽  
Bone Morphogenetic Protein 2 ◽  
Viral Gene ◽  
Morphogenetic Protein ◽  
Induced Pluripotent

Human degenerative cartilage has low regenerative potential. Chondrocyte transplantation offers a promising strategy for cartilage treatment and regeneration. Currently, chondrogenesis using human pluripotent stem cells (hiPSCs) is accomplished using human recombinant growth factors. Here, we differentiate hiPSCs into chondrogenic pellets using minicircle vectors. Minicircles are a non-viral gene delivery system that can produce growth factors without integration into the host genome. We generated minicircle vectors containing bone morphogenetic protein 2 (BMP2) and transforming growth factor beta 3 (TGFβ3) and delivered them to mesenchymal stem cell-like, hiPSC-derived outgrowth (OG) cells. Cell pellets generated using minicircle-transfected OG cells successfully differentiated into the chondrogenic lineage. The implanted minicircle-based chondrogenic pellets recovered the osteochondral defects in rat models. This work is a proof-of-concept study that describes the potential application of minicircle vectors in cartilage regeneration using hiPSCs.

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