Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem （iPS） cells from mouse mature adipocytes by forced expression of six transcription...Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem （iPS） cells from mouse mature adipocytes by forced expression of six transcription factors （Oct4, Sox2, c-Myc, Klf4, Rarγ, and Lrh1） with a piggyBac transposon-based strategy. The resulting iPS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1, and remained pluripotent on a 2i media. In vitro differen- tiation of the iPS cells showed that the cell derivatives of all three germ layers could be readily obtained through forma- tion of embryoid bodies. Most importantly, these adipocyte- derived iPS cells were capable of producing chimera with high frequencies when reintroduced into early-stage em- bryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming tech- nology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.展开更多
Objective： To explore the therapeutic ef- fect of osteogenically induced adipose-derived stem cells （ADSCs） on vascular deprivation-induced osteonecrosis of the femoral head （ONFH） in rabbit model. Methods： Vas...Objective： To explore the therapeutic ef- fect of osteogenically induced adipose-derived stem cells （ADSCs） on vascular deprivation-induced osteonecrosis of the femoral head （ONFH） in rabbit model. Methods： Vascular deprivation-induced ONFH was established by intramuscular injection of methylpre- dnisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation in adult New Zealand white rabbits. Eight weeks afLer the establishment of vascular dep- rivation-induced ONFH, animals were randomly divided into three equal groups. In Group A （control）, no therapy was given. In Group B, core decompression was performed by drilling a hole （1.2 mm in diameter） from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter. In Group C, 1 x 107 osteogenically induced ADSCs were resus- pended in 0.5 ml PBS, and then injected directly into the femoral head. Femoral head specimens were obtained at postoperative 8 weeks. The bone formation and three-di- mensional microstructure of the femoral head was evaluated by micro-computed tomography scans （u-CT）. Immunohistochemical analysis was performed to detect the expression ofosteocalcin. Angiogenesis and repair of the femoral head were observed histologically. Results： In trabecular bone at the proximal femur region, the trabecular volume was higher in Group C （130.70 mm3± 4.33 mm3） than that in Groups A （101.07 mm3±7.76 mm3） and B （107.89 mm3±8.6g mm3, P〈0.01）. Bone volume was significantly increased in Group C （40.09 mm3±6.35 mm3） than in Groups A （29.65 mm3±4.61 mm3） and B （31.80 mm3± 4.01 mm3, P〈0.01）. The trabecular number was higher in Groups C （1.58±0.25） than other two groups （1.15±0.18, 1.16± 0.21, P〈0.01）. Bone mineral density showed statistically significant difference between Groups C and A or B （375.38± 23.06） mg HA/ccm, vs （313.73 ± 19.30） mg HA/ccm and （316.09± 16.45） mg HA/ccm, P〈0.01）. Histological examination indicated that there was more new bone formation in Group C than in other groups. Conclusion： Treatment with autologous osteogenically induced ADSCs transplantation results in an enhanced osteogenesis and microstructure of the vascular deprivation-induced osteonecrosis in rabbits.展开更多
基金supported in part by the National Basic Research Program of China(2011CB504004,2010CB945500)the Strategic Program of Stem Cell(XDA01020303)+1 种基金the Knowledge Innovation Program of the Chinese Academy of Sciencesthe National Natural Science Foundation of China(90813033)as well as The Guangdong Key High-end Foreign Experts Program Fund
文摘Mature adipocytes are terminally differentiated somatic cells. Here, we report the successful generation of induced pluripotent stem （iPS） cells from mouse mature adipocytes by forced expression of six transcription factors （Oct4, Sox2, c-Myc, Klf4, Rarγ, and Lrh1） with a piggyBac transposon-based strategy. The resulting iPS cells were pluripotent as evidenced by the fact that they stained positive for alkaline phosphatase, expressed high levels of key pluripotency markers including Oct4, Nanog, and SSEA1, and remained pluripotent on a 2i media. In vitro differen- tiation of the iPS cells showed that the cell derivatives of all three germ layers could be readily obtained through forma- tion of embryoid bodies. Most importantly, these adipocyte- derived iPS cells were capable of producing chimera with high frequencies when reintroduced into early-stage em- bryos and transmitted through the germ line. This study demonstrates that the new six-factor reprogramming tech- nology facilitates the reset of the terminally differentiated adipocytes to the ground state of pluripotency, enabling us to fully explore the potential of mature adipocytes as a viable cell source for regenerative medicine.
基金This work is supported by a grant from the National Natural Science Foundation of China （30960390） and Doctoral Innovation Fund of Xinjiang Medical University （DC2010-12）.
文摘Objective： To explore the therapeutic ef- fect of osteogenically induced adipose-derived stem cells （ADSCs） on vascular deprivation-induced osteonecrosis of the femoral head （ONFH） in rabbit model. Methods： Vascular deprivation-induced ONFH was established by intramuscular injection of methylpre- dnisolone, and vascular occlusion of the capital femoral epiphysis by electrocoagulation in adult New Zealand white rabbits. Eight weeks afLer the establishment of vascular dep- rivation-induced ONFH, animals were randomly divided into three equal groups. In Group A （control）, no therapy was given. In Group B, core decompression was performed by drilling a hole （1.2 mm in diameter） from the outer cortex 2.5 cm distal to the proximal end of the greater trochanter. In Group C, 1 x 107 osteogenically induced ADSCs were resus- pended in 0.5 ml PBS, and then injected directly into the femoral head. Femoral head specimens were obtained at postoperative 8 weeks. The bone formation and three-di- mensional microstructure of the femoral head was evaluated by micro-computed tomography scans （u-CT）. Immunohistochemical analysis was performed to detect the expression ofosteocalcin. Angiogenesis and repair of the femoral head were observed histologically. Results： In trabecular bone at the proximal femur region, the trabecular volume was higher in Group C （130.70 mm3± 4.33 mm3） than that in Groups A （101.07 mm3±7.76 mm3） and B （107.89 mm3±8.6g mm3, P〈0.01）. Bone volume was significantly increased in Group C （40.09 mm3±6.35 mm3） than in Groups A （29.65 mm3±4.61 mm3） and B （31.80 mm3± 4.01 mm3, P〈0.01）. The trabecular number was higher in Groups C （1.58±0.25） than other two groups （1.15±0.18, 1.16± 0.21, P〈0.01）. Bone mineral density showed statistically significant difference between Groups C and A or B （375.38± 23.06） mg HA/ccm, vs （313.73 ± 19.30） mg HA/ccm and （316.09± 16.45） mg HA/ccm, P〈0.01）. Histological examination indicated that there was more new bone formation in Group C than in other groups. Conclusion： Treatment with autologous osteogenically induced ADSCs transplantation results in an enhanced osteogenesis and microstructure of the vascular deprivation-induced osteonecrosis in rabbits.
