Pre-transplantational Control of the Post-transplantational Fate of Human Pluripotent Stem Cell-Derived Cartilage.
Pre-transplantational Control of the Post-transplantational Fate of Human Pluripotent Stem Cell-Derived Cartilage.
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DOI：
10.1016/j.stemcr.2018.06.021
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发表时间：
2018-08-14
影响因子：
5.9
通讯作者：
Nakayama N
中科院分区：
文献类型：
--
作者：
Lee JY;Matthias N;Pothiawala A;Ang BK;Lee M;Li J;Sun D;Pigeot S;Martin I;Huard J;Huang Y;Nakayama N
Cartilage pellets generated from ectomesenchymal progeny of human pluripotent stem cells (hPSCs) in vitro eventually show signs of commitment of chondrocytes to hypertrophic differentiation. When transplanted subcutaneously, most of the surviving pellets were fully mineralized by 8 weeks. In contrast, treatment with the adenylyl cyclase activator, forskolin, in vitro resulted in slightly enlarged cartilage pellets containing an increased proportion of proliferating immature chondrocytes that expressed very low levels of hypertrophic/terminally matured chondrocyte-specific genes. Forskolin treatment also enhanced hyaline cartilage formation by reducing type I collagen gene expression and increasing sulfated glycosaminoglycan accumulation in the developed cartilage. Chondrogenic mesoderm from hPSCs and dedifferentiated nasal chondrocytes responded similarly to forskolin. Furthermore, forskolin treatment in vitro increased the frequency at which the cartilage pellets maintained unmineralized chondrocytes after subcutaneous transplantation. Thus, the post-transplantational fate of chondrocytes originating from hPSC-derived chondroprogenitors can be controlled during their genesis in vitro. Forskolin/cAMP suppresses/delays BMP-induced chondrocyte maturation in vitro Forskolin supports chondrocyte proliferation and hyaline chondrogenesis in vitro Forskolin suppresses osteogenesis and BMP signaling gene expression in cartilage In vitro forskolin treatment improves in vivo maintenance of uncalcified cartilage In this article, Naoki Nakayama and colleagues show that suppression of hypertrophic differentiation and terminal maturation of chondrocytes by forskolin/cAMP treatment during in vitro chondrogenesis from human pluripotent stem cell-derived chondroprogenitors leads to the formation of cartilage consisting of an increased proportion of proliferating, immature chondrocytes with significantly improved ability to be maintained in an unmineralized state in vivo.
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影响因子：
11.8
作者：
Ionescu, Andreia;Kozhemyakina, Elena;Nicolae, Claudia;Kaestner, Klaus H.;Olsen, Bjorn R.;Lassar, Andrew B.
通讯作者：
Lassar, Andrew B.
DOI：
10.1083/jcb.126.6.1611
发表时间：
1994-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Amizuka N;Warshawsky H;Henderson JE;Goltzman D;Karaplis AC
通讯作者：
Karaplis AC
影响因子：
2.7
作者：
Guo, J;Chung, UI;Kronenberg, HM
通讯作者：
Kronenberg, HM
影响因子：
4
作者：
Hatakeyama, Y;Tuan, RS;Shum, L
通讯作者：
Shum, L
影响因子：
4
作者：
Fischer, Jennifer;Aulmann, Antje;Richter, Wiltrud
通讯作者：
Richter, Wiltrud