Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease.
Cellular immune response to intrastriatally implanted allogeneic bone marrow stromal cells in a rat model of Parkinson's disease.
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DOI：
10.1186/1742-2094-6-17
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发表时间：
2009-06-05
影响因子：
9.3
通讯作者：
LeWitt PA
中科院分区：
文献类型：
--
作者：
Camp DM;Loeffler DA;Farrah DM;Borneman JN;LeWitt PA
骨髓基质细胞（MSC）是骨髓中的非造血前体细胞，正在研究其在中枢神经系统疾病中的治疗潜力。尽管体外研究表明MSC可能是免疫惰性的，但其移植到同种异体受体后的免疫原性尚不清楚。本研究的主要目的是研究对注射到同种异体受体（6-羟基多巴胺[6-OHDA]-半脑损伤大鼠，帕金森病[PD]的动物模型）纹状体中的MSC的细胞免疫应答，次要目的是确定这些细胞预防这些动物中黑质纹状体多巴胺耗竭和相关运动缺陷的能力。将来自两种同种异体来源（Wistar和ACI大鼠）的5-溴-2-脱氧尿苷（BrdU）标记的MSC植入成年Wistar大鼠的纹状体中，同时将6-OHDA施用到黑质中。在6-OHDA损伤和MSC移植前1 - 2周和后16-20天进行行为学测试。在移植后第22-24天进行T辅助细胞和T细胞毒性淋巴细胞、小胶质细胞/巨噬细胞和主要组织相容性I类和II类抗原的免疫细胞化学染色。用抗BrdU抗体检测MSC。由于移植过程引起的组织损伤产生了局部细胞免疫应答。出乎意料的是，两种来源的同种异体MSC在宿主纹状体中产生了强烈的细胞免疫应答;这种应答的程度在两种同种异体移植系统中相似。尽管有这些免疫反应，BrdU+细胞（推定的MSC）仍然存在于接受MSC的所有动物的纹状体中。与接受ACI MSC的大鼠相比，接受Wistar MSC的大鼠中剩余MSC的数量倾向于增加（p = 0.055）。MSC给药不能防止6-OHDA损伤动物的行为缺陷或多巴胺耗竭。当MSC植入同种异体动物的纹状体中时，引起显著的免疫应答，其不足以在移植后22-24天清除这些细胞。在本研究的实验范例中，MSC不能预防黑质纹状体多巴胺耗竭及其相关的行为缺陷。在PD或其他神经退行性疾病患者中开始使用这些细胞进行试验之前，需要进行其他研究以阐明这种免疫应答对MSC存活和功能的影响。
Marrow stromal cells (MSC), the non-hematopoietic precursor cells in bone marrow, are being investigated for therapeutic potential in CNS disorders. Although in vitro studies have suggested that MSC may be immunologically inert, their immunogenicity following transplantation into allogeneic recipients is unclear. The primary objective of this study was to investigate the cellular immune response to MSC injected into the striatum of allogeneic recipients (6-hydroxydopamine [6-OHDA]-hemilesioned rats, an animal model of Parkinson's disease [PD]), and the secondary objective was to determine the ability of these cells to prevent nigrostriatal dopamine depletion and associated motor deficits in these animals. 5-Bromo-2-deoxyuridine (BrdU) – labeled MSC from two allogeneic sources (Wistar and ACI rats) were implanted into the striatum of adult Wistar rats at the same time as 6-OHDA was administered into the substantia nigra. Behavioral tests were administered one to two weeks before and 16–20 days after 6-OHDA lesioning and MSC transplantation. Immunocytochemical staining for T helper and T cytotoxic lymphocytes, microglia/macrophages, and major histocompatibility class I and II antigens was performed on post-transplantation days 22–24. MSC were detected with an anti-BrdU antibody. Tissue injury due to the transplantation procedure produced a localized cellular immune response. Unexpectedly, both sources of allogeneic MSC generated robust cellular immune responses in the host striatum; the extent of this response was similar in the two allograft systems. Despite these immune responses, BrdU+ cells (presumptive MSC) remained in the striatum of all animals that received MSC. The numbers of remaining MSC tended to be increased (p = 0.055) in rats receiving Wistar MSC versus those receiving ACI MSC. MSC administration did not prevent behavioral deficits or dopamine depletion in the 6-OHDA-lesioned animals. MSC, when implanted into the striatum of allogeneic animals, provoke a marked immune response which is not sufficient to clear these cells by 22–24 days post-transplantation. In the experimental paradigm in this study, MSC did not prevent nigrostriatal dopamine depletion and its associated behavioral deficits. Additional studies are indicated to clarify the effects of this immune response on MSC survival and function before initiating trials with these cells in patients with PD or other neurodegenerative disorders.
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DOI：
10.1007/bf03206631
发表时间：
2004-10-01
期刊：
NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Barker, Roger A;Widner, Hakan
通讯作者：
Widner, Hakan
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
影响因子：
3.8
作者：
Arenas, E
通讯作者：
Arenas, E
影响因子：
12.7
作者：
Brandis, A;Kuder, H;Nikkhah, G
通讯作者：
Nikkhah, G
影响因子：
6.2
作者：
Coyne, Thomas M.;Marcus, Akiva J.;Woodbury, Dale
通讯作者：
Woodbury, Dale