Borlongan C V, Saporta S, Sanberg P R
Division of Neurological Surgery, Departments of Anatomy, Surgery, Neurology, Psychiatry, and Pharmacology, University of South Florida College of Medicine, Tampa, Florida, 33612, USA.
Exp Neurol. 1998 Jun;151(2):203-14. doi: 10.1006/exnr.1998.6790.
Possible biologic treatments for Parkinson's disease, a disorder caused by the deterioration of dopaminergic neurons bridging the nigrostriatal system, have recently focused on fetal cell transplantation. Because of ethical and tissue availability issues concerning fetal cell transplantation, alternative cell sources are being developed. The adrenal medulla has been used as a cell transplant source because of the capacity of the cells to provide catecholamines and to transform into a neuronal phenotype. However, adrenal tissue transplants have shown limited success, primarily because of their lack of long-term viability. Recently, seeding adrenal chromaffin cells on microcarrier beads has been shown to enhance the cell viability following neural transplantation. In the present study, we further investigated whether transplantation of rat adrenal chromaffin cells seeded on microcarrier beads into the striatum of 6-hydroxydopamine-induced hemiparkinsonian rats would result in a sustained functional recovery. Behavioral tests using the apomorphine-induced rotational and elevated body swing tests up to 12 months posttransplantation revealed a significant behavioral recovery in animals that received adrenal chromaffin cells seeded on microcarrier beads compared to animals that received adrenal chromaffin cells alone, medium alone, or beads alone. Histological examination of tissue at 14 months posttransplantation revealed evidence of tyrosine hydroxylase-positive cells and an on-going glial response in animals transplanted with adrenal chromaffin cells seeded on microcarrier beads, in contrast to absence of such immunoreactive responses in the other groups. These findings support a facilitator role for microcarrier beads in transplantation of adrenal chromaffin cells or other cells that are easily rejected by the CNS.
帕金森病是一种由连接黑质纹状体系统的多巴胺能神经元退化引起的疾病,其可能的生物治疗方法近来聚焦于胎儿细胞移植。由于胎儿细胞移植存在伦理和组织可用性问题,人们正在开发替代细胞来源。肾上腺髓质已被用作细胞移植来源,因为这些细胞能够提供儿茶酚胺并转化为神经元表型。然而,肾上腺组织移植的成功率有限,主要是因为它们缺乏长期生存能力。最近研究表明,将肾上腺嗜铬细胞接种在微载体珠上可提高神经移植后的细胞活力。在本研究中,我们进一步研究了将接种在微载体珠上的大鼠肾上腺嗜铬细胞移植到6-羟基多巴胺诱导的偏侧帕金森病大鼠纹状体内是否会导致持续的功能恢复。在移植后长达12个月的时间里,使用阿扑吗啡诱导的旋转和抬高身体摆动试验进行行为测试,结果显示,与单独接受肾上腺嗜铬细胞、单独接受培养基或单独接受珠子的动物相比,接受接种在微载体珠上的肾上腺嗜铬细胞的动物有显著的行为恢复。移植后14个月对组织进行组织学检查发现,接种在微载体珠上的肾上腺嗜铬细胞移植的动物体内有酪氨酸羟化酶阳性细胞的证据以及持续的胶质细胞反应,相比之下,其他组没有这种免疫反应。这些发现支持了微载体珠在肾上腺嗜铬细胞或其他容易被中枢神经系统排斥的细胞移植中起促进作用。