Beijing Institute for Neuroscience, Capital Medical University, Beijing 100069, China.
J Biomed Mater Res A. 2013 Feb;101(2):599-606. doi: 10.1002/jbm.a.34331. Epub 2012 Oct 23.
The neurogenesis amount in central nervous system (CNS) stimulated by the injury or diseases is so small that neural stem cells (NSCs) cannot specifically differentiate into the ideal phenotypes to repair the injured CNS. The transplanted exogenous NSCs also have such problems as poor survival and insufficient neuronal differentiation. In this study, the behavior of NSCs from the spinal cord of adult rats was compared at the neurosphere level after the respective addition of the brain-derived neurotrophic factor (BDNF) daily, the BDNF-loaded plasma-collagen matrix, the plasma-collagen matrix alone, or the defined medium alone. The results suggested that the BDNF, either in the control release form or in the soluble form, initiated NSCs proliferation and differentiation by activating receptors Trk B and p75NTR. BDNF also increased the differentiation percentage of adult NSCs into neurons and supported the long-term cell survival and growth. The BDNF was stably released by the plasma-collagen matrix for up to 21 days. The plasma-collagen matrix alone showed its biocompatibility with cells by facilitating the adhesion, survival, and differentiation of NSCs. The NSCs in the defined medium alone group showed poor survival and a very low level of neuronal differentiation and proliferation abilities than above three groups. This study suggested that the BDNF-loaded plasma-collagen matrix may provide a promising means to resolve either the poor survival and insufficient neuronal differentiation of transplanted exogenous NSCs, or stimulating the intrinsic NSCs to proliferate and differentiate into neurons so as to repair the injured adult CNS.
中枢神经系统(CNS)在受到损伤或疾病刺激时,其神经发生量非常小,以至于神经干细胞(NSCs)无法特异性地分化为理想的表型来修复受损的 CNS。移植的外源性 NSCs 也存在诸如生存能力差和神经元分化不足等问题。在这项研究中,比较了成年大鼠脊髓来源的 NSCs 在分别添加每日脑源性神经营养因子(BDNF)、BDNF 负载的血浆胶原基质、单独的血浆胶原基质或单独的定义培养基后,在神经球水平上的行为。结果表明,BDNF 以控制释放形式或可溶性形式激活受体 Trk B 和 p75NTR,启动 NSCs 增殖和分化。BDNF 还增加了成年 NSCs 向神经元分化的百分比,并支持细胞的长期存活和生长。BDNF 可通过血浆胶原基质稳定释放长达 21 天。单独的血浆胶原基质通过促进 NSCs 的黏附、存活和分化显示出其与细胞的生物相容性。单独的定义培养基中的 NSCs 比以上三组的存活能力差,神经元分化和增殖能力非常低。本研究表明,BDNF 负载的血浆胶原基质可能为解决移植的外源性 NSCs 生存能力差和神经元分化不足,或刺激内源性 NSCs 增殖和分化为神经元,从而修复成年损伤的 CNS 提供一种有前途的方法。
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