scholarly journals Direct Conversion of Human Pluripotent Stem Cells to Osteoblasts With a Small Molecule

2018 ◽  
Vol 44 (1) ◽  
Author(s):  
Heemin Kang ◽  
Yu‐Ru V. Shih ◽  
Shyni Varghese
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Direct Conversion ◽  
Human Pluripotent Stem Cells

scholarly journals Small molecule–driven direct conversion of human pluripotent stem cells into functional osteoblasts

2016 ◽  
Vol 2 (8) ◽  
pp. e1600691 ◽  
Author(s):  
Heemin Kang ◽  
Yu-Ru V. Shih ◽  
Manando Nakasaki ◽  
Harsha Kabra ◽  
Shyni Varghese
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Bone Matrix ◽  
Induced Pluripotent Stem Cell ◽  
Direct Conversion ◽  
Human Pluripotent Stem Cells ◽  
Tissue Specific

The abilities of human pluripotent stem cells (hPSCs) to proliferate without phenotypic alteration and to differentiate into tissue-specific progeny make them a promising cell source for regenerative medicine and development of physiologically relevant in vitro platforms. Despite this potential, efficient conversion of hPSCs into tissue-specific cells still remains a challenge. Herein, we report direct conversion of hPSCs into functional osteoblasts through the use of adenosine, a naturally occurring nucleoside in the human body. The hPSCs treated with adenosine not only expressed the molecular signatures of osteoblasts but also produced calcified bone matrix. Our findings show that the adenosine-mediated osteogenesis of hPSCs involved the adenosine A2bR. When implanted in vivo, using macroporous synthetic matrices, the human induced pluripotent stem cell (hiPSC)–derived donor cells participated in the repair of critical-sized bone defects through the formation of neobone tissue without teratoma formation. The newly formed bone tissues exhibited various attributes of the native tissue, including vascularization and bone resorption. To our knowledge, this is the first demonstration of adenosine-induced differentiation of hPSCs into functional osteoblasts and their subsequent use to regenerate bone tissues in vivo. This approach that uses a physiologically relevant single small molecule to generate hPSC-derived progenitor cells is highly appealing because of its simplicity, cost-effectiveness, scalability, and impact in cell manufacturing, all of which are decisive factors for successful translational applications of hPSCs.

scholarly journals Small-Molecule-Driven Hepatocyte Differentiation of Human Pluripotent Stem Cells

2015 ◽  
Vol 4 (5) ◽  
pp. 939-952 ◽  
Author(s):  
Richard Siller ◽  
Sebastian Greenhough ◽  
Elena Naumovska ◽  
Gareth J. Sullivan
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Hepatocyte Differentiation

scholarly journals Combined small-molecule inhibition accelerates developmental timing and converts human pluripotent stem cells into nociceptors

2012 ◽  
Vol 30 (7) ◽  
pp. 715-720 ◽  
Author(s):  
Stuart M Chambers ◽  
Yuchen Qi ◽  
Yvonne Mica ◽  
Gabsang Lee ◽  
Xin-Jun Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells ◽  
Developmental Timing ◽  
Small Molecule Inhibition

scholarly journals Direct conversion of human pluripotent stem cells into cranial motor neurons using a piggyBac vector

2018 ◽  
Vol 29 ◽  
pp. 189-196 ◽  
Author(s):  
Riccardo De Santis ◽  
Maria Giovanna Garone ◽  
Francesca Pagani ◽  
Valeria de Turris ◽  
Silvia Di Angelantonio ◽  
...  
Keyword(s):  
Stem Cells ◽  
Motor Neurons ◽  
Pluripotent Stem Cells ◽  
Direct Conversion ◽  
Human Pluripotent Stem Cells ◽  
Piggybac Vector

scholarly journals Efficiently generate functional hepatic cells from human pluripotent stem cells by complete small-molecule strategy

2021 ◽  
Author(s):  
Tingcai Pan ◽  
Ning Wang ◽  
Jiaye Zhang ◽  
Fan Yang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factors ◽  
Small Molecules ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Cost Effective ◽  
Human Pluripotent Stem Cells ◽  
Scale Production ◽  
Hepatic Cells ◽  
Cell Based Therapy

Abstract Background: Various methods have been developed to generate hepatic cells from human pluripotent stem cells (hPSCs) that rely on the combined use of multiple expensive growth factors, limiting industrial-scale production and widespread applications. Small molecules offer an attractive alternative to growth factors for producing hepatic cells since they are more economical and relatively stable. Methods: We dissect small-molecule combinations and identify the ideal cocktails to achieve an optimally efficient and cost-effective strategy for hepatic cells differentiation, expansion, and maturation.Results: We demonstrated that small-molecule cocktail CIP efficiently induced definitive endoderm (DE) formation via increased endogenous TGF-β/Nodal signaling. Furthermore, we identified that combining Vitamin C, Dihexa, and Forskolin (VDF) could substitute growth factors to induce hepatic specification. The obtained hepatoblasts (HBs) could subsequently expand and mature into functional hepatocyte-like cells (HLCs) by the established chemical formulas. Thus, we established a stepwise strategy with complete small molecules for efficiently producing scalable HBs and functionally matured HLCs. The small-molecule derived HLCs displayed typical functional characteristics as mature hepatocytes in vitro and repopulating injured liver in vivo. Conclusion: Our current small-molecule based hepatic generation protocol presents an efficient and cost-effective platform for the large-scale production of functional human hepatic cells for cell-based therapy and drug discovery using.

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