肌萎缩侧索硬化
医学
造血干细胞移植
干细胞
病理
脐带血
神经炎症
移植
造血
免疫学
疾病
生物
内科学
遗传学
作者
Stanley H. Appel,J. Engelhardt,Jenny S. Henkel,L. Siklós,David R. Beers,Albert Yen,Ericka P. Simpson,Yongquan Luo,George Carrum,Helen E. Heslop,Malcolm K. Brenner,Uday Popat
出处
期刊:Neurology
[Ovid Technologies (Wolters Kluwer)]
日期:2008-10-20
卷期号:71 (17): 1326-1334
被引量:135
标识
DOI:10.1212/01.wnl.0000327668.43541.22
摘要
Amyotrophic lateral sclerosis (ALS), an inexorably progressive motoneuron disease, is accompanied by significantly increased markers of inflammation. These inflammatory constituents could protect, harm, do neither, or do both.Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in patients with sporadic ALS to suppress neuroinflammation and improve clinical outcomes after CNS engraftment.Six patients with definite ALS received total body irradiation followed by peripheral blood HSCT infusion from human leukocyte antigen identically matched sibling donors. Disease progression and survival were assessed monthly and compared with matched historic database patients. Autopsy samples from brain and spinal cord were examined immunohistochemically and by quantitative reverse-transcriptase polymerase chain reaction. Donor-derived DNA in brain and spinal cord tissue was evaluated for the extent of chimerism.No clinical benefits were evident. Four patients were 100% engrafted; postmortem tissue examination in two of the 100% engrafted patients demonstrated 16% to 38% donor-derived DNA at sites with motoneuron pathology, which may correspond to the observed increased CD68 or CD1a-positive cells. Neither donor DNA nor increased cell numbers were found in several unaffected brain regions. A third minimally engrafted patient had neither donor DNA nor increased infiltrating cells in the CNS.This study demonstrates that peripheral cells derived from donor hematopoietic stem cells can enter the human CNS primarily at sites of motoneuron pathology and engraft as immunomodulatory cells. Although unmodified hematopoietic stem cells did not benefit these sporadic amyotrophic lateral sclerosis patients, such cells may provide a cellular vehicle for future CNS gene therapy.
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