Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord
Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord
复制标题
DOI：
10.1006/exnr.2002.7981
复制
发表时间：
2002-10-01
影响因子：
5.3
通讯作者：
Whittemore, SR
中科院分区：
文献类型：
--
作者：
Cao, QL;Howard, RM;Whittemore, SR
移植到成年正常和损伤脊髓的多能神经干细胞的分化仅限于神经胶质谱系，提示在移植前体外向神经元谱系诱导和/或改变宿主环境可能是启动和增加神经元分化所必需的。在本研究中，我们研究了神经限制性前体(NRP)移植到正常和挫伤的成年大鼠脊髓中的分化情况。在有FGF2和NT3存在的情况下，NRPs通过多个传代增殖，而在存在维甲酸和不存在FGF2的情况下，NRPs在体外仅分化为神经元。分化的NRP表达GABA、甘氨酸、谷氨酸和ChAT。未分化NRP植入成年正常脊髓2周~2个月后，所有动物均可见大量存活细胞。大多数分化为BetaIII-微管蛋白阳性神经元。一些移植的NRP表达GABA，少数是谷氨酸和ChAT阳性。NRPs也被移植到成年大鼠脊髓挫伤的震中。移植后2周至2个月，部分移植的NRPs仍有未分化的Nestin阳性细胞。少量MAP2或βIII微管蛋白阳性神经元。然而，没有观察到GABA、谷氨酸或ChAT的表达。这些结果表明，NRPs在正常成年大鼠脊髓中可以分化为不同类型的神经元，但在损伤的脊髓中这种分化被抑制。为了促进神经元的替换，可能需要对损伤脊髓的微环境进行操作。(C)2002年埃尔塞维尔科学公司(美国)。
Differentiation of pluripotent neural stem cells engrafted into the adult normal and injured spinal cord is restricted to the glial lineage, suggesting that in vitro induction toward a neuronal lineage prior to transplantation and/or modification of the host environment may be necessary to initiate and increase the differentiation of neurons. In the present study, we investigated the differentiation of neuronal-restricted precursors (NRPs) grafted into the normal and contused adult rat spinal cord. NRPs proliferated through multiple passages in the presence of FGF2 and NT3 and differentiated into only neurons in vitro in the presence of retinoic acid and the absence of FGF2. Differentiated NRPs expressed GABA, glycine, glutamate, and ChAT. Two weeks to 2 months after engraftment of undifferentiated NRPs into adult normal spinal cord, large numbers of surviving cells were seen in all of the animals. The majority differentiated into betaIII-tubulin-positive neurons. Some transplanted NRPs expressed GABA and small numbers were glutamate- and ChAT-positive. NRPs were also transplanted into the epicenter of the contused adult rat spinal cord. Two weeks to 2 months after transplantation, some engrafted NRPs remained undifferentiated nestin-positive cells. Small numbers were MAP2- or betaIII-tubulin-positive neurons. However, the expression of GABA, glutamate, or ChAT was not observed. These results show that NRPs can differentiate into different types of neurons in the normal adult rat spinal cord, but that such differentiation is inhibited in the injured spinal cord. Manipulation of the microenvironment in the injured spinal cord will likely be necessary to facilitate neuronal replacement. (C) 2002 Elsevier Science (USA).