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将自然流产的人类胎儿组织移植到帕金森病啮齿动物模型中。

Transplantation of human fetal tissue from spontaneous abortions to a rodent model of Parkinson's disease.

作者信息

Kondoh T, Pundt L L, Blount J P, Conrad J A, Low W C

机构信息

Department of Neurosurgery, University of Minnesota Medical School, Minneapolis 55455, USA.

出版信息

Cell Transplant. 1996 Jan-Feb;5(1):69-75. doi: 10.1177/096368979600500112.

Abstract

The use of human fetal tissue from elective abortions for cell transplantation therapies has been the subject of considerable controversy. Because of concerns regarding the use of tissue from elective abortions, tissue from spontaneous abortions has been suggested as an alternate donor source. In the present study we have evaluated human fetal tissue from spontaneous abortions to assess its viability, growth potential, and functional expression. Viable cells (Grade I) from a donor (7 wk postconception) were transplanted as a suspension into the striatum of rats with unilateral 6-OHDA lesions of the nigrostriatal pathway. A second group of animals received solid grafts of tissue from a Grade I donor 14 wk postconception. Tissue from Grade II and III specimens were not sufficiently viable for transplantation. Locomotor responses were monitored over a period of 15 wk and revealed an amelioration of rotational asymmetry by animals that received tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor showed no functional improvement. We found numerous graft-derived tyrosine hydroxylase (TH) immunopositive neurons contained within the transplantation site, and a rich plexus of TH-immunopositive fibers extending into the striatum of animals receiving tissue from the 7 wk donor. Animals receiving tissue from the 14 wk donor exhibited tissue necrosis at the transplant site and were devoid of TH-immunopositive neurons. These results suggest that human fetal ventral mesencephalic cells from spontaneous abortions can survive and develop after transplantation, and rectify locomotor deficits associated with experimental parkinsonism if the donor tissue is of the appropriate gestational age at the time of implantation. Our study further suggests, however, that the availability of tissue from spontaneous abortions of sufficient viability is quite limited and may thus restrict its potential use in cell transplantation therapies for Parkinson's disease.

摘要

将选择性流产的人类胎儿组织用于细胞移植治疗一直是颇具争议的话题。由于对使用选择性流产组织存在担忧,有人提出将自然流产的组织作为替代供体来源。在本研究中,我们评估了自然流产的人类胎儿组织,以评估其活力、生长潜力和功能表达。将来自一名供体(受孕后7周)的活细胞(I级)作为悬浮液移植到黑质纹状体通路单侧6-羟基多巴胺损伤的大鼠纹状体中。第二组动物接受了来自受孕后14周I级供体的组织实体移植。来自II级和III级标本的组织活力不足以用于移植。在15周的时间内监测运动反应,结果显示,接受7周供体组织的动物的旋转不对称性有所改善。接受14周供体组织的动物未表现出功能改善。我们发现移植部位有大量移植来源的酪氨酸羟化酶(TH)免疫阳性神经元,并且有丰富的TH免疫阳性纤维丛延伸到接受7周供体组织的动物的纹状体中。接受14周供体组织的动物在移植部位出现组织坏死,且没有TH免疫阳性神经元。这些结果表明,自然流产的人类胎儿腹侧中脑细胞在移植后能够存活并发育,如果供体组织在植入时具有合适的胎龄,则可以纠正与实验性帕金森病相关的运动缺陷。然而,我们的研究进一步表明,具有足够活力的自然流产组织的可用性相当有限,因此可能会限制其在帕金森病细胞移植治疗中的潜在应用。

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