Overexpression of Bcl-2 promotes survival and differentiation of neuroepithelial stem cells after transplantation into rat aganglionic colon.
Overexpression of Bcl-2 promotes survival and differentiation of neuroepithelial stem cells after transplantation into rat aganglionic colon.
复制标题
Bcl-2过表达促进神经上皮干细胞移植至大鼠无神经节结肠后的存活和分化
DOI：
10.1186/scrt155
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发表时间：
2013-01-16
影响因子：
7.5
通讯作者：
Wu R
中科院分区：
文献类型：
--
作者：
Liu W;Yue W;Wu R
神经干细胞移植是一种很有前途的工具，在各种动力障碍的肠神经系统的恢复。然而，移植后有限的细胞活力限制了其再生能力。本研究旨在探讨过表达抗凋亡基因Bcl-2的神经上皮干细胞（neuroepithelial stem cell，NESC）移植对大鼠无神经节结肠移植细胞存活、分化和功能的影响。从胚胎大鼠（胚胎11.5天）的神经管中分离NESC，并操作以过表达Bcl-2基因。移植到苯扎氯铵诱导的大鼠无神经节结肠后，移植细胞在结肠切片中可见。分别在移植后1、4和8周评估植入细胞的凋亡和分化。移植后8周，通过测量肌肉条对电场刺激的反应来评估结肠的神经元功能。与载体NESC移植组相比，Bcl-2-NESC移植在1周时减少了移植物内的细胞凋亡。我们的研究结果还表明，Bcl-2的过度表达在移植的NESC促进分化为PGP9.5阳性和神经元型一氧化氮合酶阳性神经元在8周的评估。此外，Bcl-2-NESC移植组结肠条的电刺激松弛也显著增加。转基因过表达Bcl-2的NESC移植可能对增强移植细胞在成人肠道环境中的存活和神经发生以及改善广泛的胃肠动力障碍后干细胞治疗的功效具有价值。
Neural stem cell transplantation is a promising tool for the restoration of the enteric nervous system in a variety of motility disorders. However, limited cell viability after transplantation has restricted its regenerative capacity. The aim of this study was to evaluate the effect of transplantation of neuroepithelial stem cell (NESC) overexpressing anti-apoptotic gene Bcl-2 on the survival, differentiation and function of grafted cells in rat aganglionic colon. NESCs were isolated from neural tube of embryonic rat (embryonic day 11.5) and manipulated to overexpress the Bcl-2 gene. After transplantation into the benzalkonium chloride-induced rat aganglionic colon, grafted cells were visualized in colonic sections. Apoptosis and differentiation of the implanted cells were assessed 1, 4 and 8 weeks post transplantation, respectively. Eight weeks post transplantation, neuronal function of the colon was assessed by measuring the response of muscle strips to electrical field stimulation. Transplantation with Bcl-2-NESCs reduced apoptosis within the transplant at 1 week compared with the vector-NESC grafted group. Our findings also indicated that overexpression of Bcl-2 in the transplanted NESCs enhanced differentiation into PGP9.5-positive and neuronal nitric oxide synthase-positive neurons at 8-week assessment. Moreover, electrical field stimulation-induced relaxation of colonic strips was also significantly increased in the Bcl-2-NESC grafted group. Transplantation of NESCs genetically modified to overexpress Bcl-2 may have value for enhancing survival and neurogenesis of grafted cells in the adult gut environment and for improving the efficacy of stem cell therapy following a broad range of gastrointestinal motility disorders.
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影响因子：
3.3
作者：
FREEMAN, TB;SANBERG, PR;KORDOWER, JH
通讯作者：
KORDOWER, JH
影响因子：
3.3
作者：
Holm, KH;Cicchetti, F;Isacson, O
通讯作者：
Isacson, O
DOI：
10.1097/00004647-200110000-00011
发表时间：
2001-10-01
影响因子：
6.3
作者：
Manoonkitiwongsa, PS;Jackson-Friedman, C;Lyden, PD
通讯作者：
Lyden, PD
影响因子：
29.4
作者：
Micci, MA;Kahrig, KM;Pasricha, PJ
通讯作者：
Pasricha, PJ
影响因子：
2.4
作者：
SATO, A;YAMAMOTO, M;SAKATA, K
通讯作者：
SAKATA, K