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Ye X.,Tongji University | Yin X.,Shanghai Minhang Central Hospital | Yang D.,Medical University | Tan J.,Tongji University | Liu G.,Tongji University
Tissue Engineering - Part C: Methods | Year: 2012

Tissue engineering approaches using the combination of porous ceramics and bone marrow mesenchymal stem cells (BMSCs) represent a promising bone substitute for repairing large bone defects. Nevertheless, optimal conditions for constructing tissue-engineered bone have yet to be determined. It remains unclear if transplantation of predifferentiated BMSCs is superior to undifferentiated BMSCs or freshly isolated bone marrow mononucleated cells (BMNCs) in terms of new bone formation in vivo. The aim of this study was to investigate the effect of in vitro osteogenic differentiation (β-glycerophosphate, dexamethasone, and l-ascorbic acid) of human BMSCs on the capability to form tissue-engineered bone in unloaded conditions after subcutaneous implantation in nude mice. After isolation from human bone marrow aspirates, BMNCs were divided into three parts: one part was seeded onto porous beta-tricalcium phosphate ceramics immediately and transplanted in a heterotopic nude mice model; two parts were expanded in vitro to passage 2 before cell seeding and in vivo transplantation, either under osteogenic conditions or not. Animals were sacrificed for micro-CT and histological evaluation at 4, 8, 12, 16, and 20 weeks postimplantation. The results showed that BMSCs differentiated into osteo-progenitor cells after induction, as evidenced by the altered cell morphology and elevated alkaline phosphatase activity and calcium deposition, but their clonogenicity, proliferating rate, and seeding efficacy were not significantly affected by osteogenic differentiation, compared with undifferentiated cells. Extensive new bone formed in the pores of all the scaffolds seeded with predifferentiated BMSCs at 4 weeks after implantation, and maintained for 20 weeks. On the contrary, scaffolds containing undifferentiated BMSCs revealed limited bone formation only in 1 out of 6 cases at 8 weeks, and maintained for 4 weeks. For scaffolds with BMNCs, woven bone was observed sporadically only in one case at 8 weeks. Overall, this study suggests that ectopic osteogenesis of cell/scaffold composites is more dependent on the in vitro expansion condition, and osteo-differentiated BMSCs hold the highest potential concerning in vivo bone regeneration. © 2012. Mary Ann Liebert, Inc.

Gu W.,Shanghai Minhang Central Hospital | Gu W.,Shanghai JiaoTong University | Zhang F.,Shanghai JiaoTong University | Xue Q.,Shanghai JiaoTong University | And 3 more authors.
Neurological Research | Year: 2012

It has been demonstrated that bone mesenchymal stromal cells (BMSCs) stimulate neurite outgrowth from dorsal root ganglion (DRG) neurons. The present in vitro study tested the hypothesis that BMSCs stimulate the neurite outgrowth from spinal neurons by secreting neurotrophic factors. Spinal neurons were cocultured with BMSCs, fibroblasts and control medium in a non-contact system. Neurite outgrowth of spinal neurons cocultured with BMSCs was significantly greater than the neurite outgrowth observed in neurons cultured with control medium or with fibroblasts. In addition, BMSC-conditioned medium increased the length of neurites from spinal neurons compared to those of neurons cultured in the control medium or in the fibroblasts-conditioned medium. BMSCs expressed brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). The concentrations of BDNF and GDNF in BMSCconditioned medium were 132±12 and 70±6 pg ml -1, respectively. The addition of anti-BDNF and anti-GDNF antibodies to BMSC-conditioned medium partially blocked the neurite-promoting effect of the BMSC-conditioned medium. In conclusion, our results demonstrate that BMSCs promote neurite outgrowth in spinal neurons by secreting soluble factors. The neurite-promoting effect of BMSCs is partially mediated by BDNF and GDNF. © W. S. Maney & Son Ltd 2012.

Gu W.,Shanghai JiaoTong University | Zhang F.,Shanghai JiaoTong University | Xue Q.,Shanghai JiaoTong University | Ma Z.,Shanghai Minhang Central Hospital | And 2 more authors.
Neuropathology | Year: 2010

It has been demonstrated that transplantation of bone marrow mesenchymal stem cells (BMSCs) improves recovery of injured spinal cord in animal models. However, the mechanism of how BMSCs promote repair of injured spinal cord remains under investigation. The present study investigated the neural differentiation of BMSCs, the lesion volume and axonal regrowth of injured spinal cord after transplantation. Seven days after spinal cord injury, 3 × 105 BMSCs or PBS (control) was delivered into the injury epicenter of the spinal cord. At 8 weeks after spinal cord injury, transplantation of BMSCs reduced the volume of cavity and increased spared white matter as compared to the control. BMSCs did not express the cell marker of neurons, astrocytes and oligodendrocytes in injured spinal cord. Transmission electron microscopic examination displayed an increase in the number of axons in BMSC rats. The effect of BMSCs on growth of neuronal process was further investigated by using a coculture system. The length and the number of neurites from spinal neurons significantly increased when they cocultured with BMSCs. PCR and immunochemical analysis showed that BMSCs expressed brain-derived neurotrophic factor (BDNF) and glia cell line-derived neurotrophic factor (GDNF). These findings demonstrate that transplantation of BMSCs reduces lesion volume and promotes axonal regrowth of injured spinal cord. © 2009 Japanese Society of Neuropathology.

Li H.,Tongji University | Gong Q.,Shanghai Minhang Central Hospital | Shao J.,Shanghai Minhang Central Hospital | Liu X.,Tongji University | Zhao Y.,Tongji University
Pakistan Journal of Medical Sciences | Year: 2014

Results: Among diabetes patients, patients with OSAS have lower glycated hemoglobin, platelet count, thrombocytocrit, MMSE score and lowest mean arterial oxygen than non-OSAS patients; cognitive dysfunction state and glycemic control of patients are related to their diabetic duration, and then along with increase of diabetic duration, glycemic control becomes poor, so that cognitive dysfunction becomes more and more obvious.Conclusion: Along with increased diabetic duration in type 2 diabetes accompanied with OSAS, glycemic control becomes poor, so that cognitive dysfunction more easily occurs. Meanwhile, coagulation function of blood system in OSAS patients with diabetes is impacted to some extent.Objective: To investigate cognitive dysfunction of type 2 diabetes patients accompanied with obstructive sleep apnea syndrome (OSAS), and to analyze its relevant characteristics.Methods: Total 115 type 2 diabetes patients were divided into OSAS group (O group, n=83) and non-OSAS group (N group, n=32); Physical examination patients (C1 group, n=64) and OSAS patients without diabetes (C2 group, n=47) served as the control group. Apnea-hypopnea index (AHI), nocturnal lowest saturation of pulse oxygen (LSPO2) and simple mental state examination scale (MMSE) were evaluated. © 2014, Professional Medical Publications. All rights reserved.

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