Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks

Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks
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DOI:
10.1016/j.expneurol.2004.06.023
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发表时间:
2004-11-01
影响因子:
5.3
通讯作者:
Weiss, ML
Weiss, ML
中科院分区:
医学2区
文献类型:
--
作者:
Medicetty, S;Bledsoe, AR;Weiss, ML

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以前的工作表明,猪脐带基质(pUCM)细胞是一种原始干细胞,这些细胞可以在中枢或外周注射到未接受免疫抑制治疗的大鼠后恢复。为了确定脑移植后pUCM细胞的安全性和增殖潜力,将约150个pUCM细胞移植到先前接受神经毒素6-羟基多巴胺(6-OHDA)纹状体注射的大鼠的脑中。预先将pUCM细胞工程化以表达增强型绿色荧光蛋白(eGFP);以这种方式,鉴定移植细胞。大鼠未接受免疫抑制治疗。没有术后并发症,动物在移植后茁壮成长。分别于移植后2、4、6、8周处死2只大鼠,观察移植细胞的形态、大小、数量及酪氨酸羟化酶(TH)阳性移植细胞的百分率。移植的pUCM细胞的大小分布是单峰和正常的,平均大小在2- 8周的存活期内显著增加。pUCM细胞的数量从移植后2周存活期的约5400个细胞增加到8周存活期的约20,000个细胞。TH阳性pUCM细胞的百分比从2周存活期的约1%增加到8周存活期的约6%。在任何时间均无明显宿主免疫应答的证据;例如,移植部位无CD-4、CD-8、CD-11b、CD-161细胞蓄积。这些结果表明,pUCM细胞移植和增殖,而不需要免疫抑制。这些发现还表明,一个子集的pUCM细胞可以分化为TH阳性细胞后8周内移植到6-OHDA损伤的大鼠脑。(C)2004爱思唯尔公司All rights reserved.
Previous work indicated that pig umbilical cord matrix (pUCM) cells are a type of primitive stem cell and that these cells could be recovered after central or peripheral injection into rats that did not receive immune suppression therapy. To determine the safety and proliferation potential of pUCM cells after brain transplantation, approximately 150 pUCM cells were transplanted into the brains of rats that previously received a striatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). The pUCM cells were previously engineered to express enhanced green fluorescent protein (eGFP); in this way, the graft cells were identified. The rats did not receive immune suppression therapy. There were no postsurgical complications and the animals thrived following transplantation. At 2, 4, 6, and 8 weeks after transplantation, two rats were sacrificed and the morphology, size and number of graft cells, and the percentage of tyrosine hydroxylase (TH)-positive graft cells were determined. The size distribution of the grafted pUCM cells was unimodal and normal, and the average size increased significantly over the 2- to 8-week survival period. The number of pUCM cells increased from approximately 5400 cells at the 2-week survival period post-transplantation to approximately 20,000 cells at the 8-week survival period. There was an increase in the percentage of TH-positive pUCM cells from approximately 1% at the 2-week survival period to approximately 6% at the 8-week survival period. There was no evidence of a significant host immune response at any time; for example, no accumulation of CD-4, CD-8, CD-11b, CD-161 cells in the transplantation site. These results suggest that pUCM cells engraft and proliferate without requiring immune suppression. These findings also suggest that a subset of pUCM cells can differentiate into TH-positive cells within 8 weeks after transplantation into the 6-OHDA lesioned rat brain. (C) 2004 Elsevier Inc. All rights reserved.