Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain
Transplantation of neural progenitors enhances production of endogenous cells in the impaired brain
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DOI：
10.1038/sj.mp.4002084
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发表时间：
2008-02-01
影响因子：
11
通讯作者：
Yanai, J.
中科院分区：
文献类型：
--
作者：
Ben-Shaanan, T. L.;Ben-Hur, T.;Yanai, J.
移植神经祖细胞已被证明可以逆转多种神经行为缺陷。虽然他们的作用，取代受伤的细胞和恢复受损的电路已被证明，它被广泛接受，这不是唯一的机制，因为治疗可以发生，即使当移植的细胞数量不足时被发现。我们假设，移植的神经祖细胞发挥其治疗作用的一个主要机制是通过增强内源性细胞的生产。因此，在同种异体移植模型中，产前暴露于海洛因的遗传异质性（HS）小鼠通过将其母亲暴露于海洛因（妊娠第9-18天10 mg kg（-1）海洛因），使其海马神经行为功能出现缺陷。海马损伤通过Morris迷宫中的表现缺陷来证实（P < 0.009），并且观察到齿状回中的内源性细胞的产生减少39%。在出生后第35天，他们接受了HS衍生的神经祖细胞移植，然后重复注射溴脱氧尿苷。移植使内源性细胞产生恢复到正常水平（P < 0.006），并逆转了行为缺陷（P < 0.03），尽管只有0.0334%的移植神经祖细胞存活，并且它们主要分化为星形胶质细胞。一项免疫学研究表明，巨噬细胞和T细胞的存在是移植细胞缺乏的可能解释。这项研究表明，神经祖细胞的治疗作用的一种机制，内源性细胞的生产的增强，通过使用神经祖细胞或通过类似的细胞诱导技术，指向未来的临床应用在这个方向。
Grafting of neural progenitors has been shown to reverse a wide variety of neurobehavioral defects. While their role of replacing injured cells and restoring damaged circuitries has been shown, it is widely accepted that this cannot be the only mechanism, as therapy can occur even when an insufficient number of transplanted cells are found. We hypothesized that one major mechanism by which transplanted neural progenitors exert their therapeutic effect is by enhancing endogenous cells production. Consequently, in an allographic model of transplantation, prenatally heroin-exposed genetically heterogeneous (HS) mice were made defective in their hippocampal neurobehavioral function by exposing their mothers to heroin (10 mg kg(-1) heroin on gestation days 9-18). Hippocampal damage was confirmed by deficient performance in the Morris maze (P < 0.009), and decreased production of endogenous cells in the dentate gyrus by 39% was observed. On postnatal day 35, they received an HS-derived neural progenitors transplant followed by repeated bromodeoxyuridine injections. The transplant returned endogenous cells production to normal levels (P < 0.006) and reversed the behavioral defects (P < 0.03), despite the fact that only 0.0334% of the transplanted neural progenitors survived and that they differentiated mainly to astrocytes. An immunological study demonstrated the presence of macrophages and T cells as a possible explanation for the paucity of the transplanted cells. This study suggests one mechanism for the therapeutic action of neural progenitors, the enhancement of the production of endogenous cells, pointing to future clinical applications in this direction by use of neural progenitors or by analogous cell-inducing techniques.