Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)
Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)
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DOI：
10.1038/sj.bmt.1703650
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发表时间：
2002-08-01
影响因子：
4.8
通讯作者：
Krivit, W
中科院分区：
文献类型：
--
作者：
Koç, ON;Day, J;Krivit, W
Hurler综合征（粘多糖类沉积症IH型）和异染性脑白质营养不良（MLD）患者出现严重的骨骼和神经缺陷，限制了他们的生存。异基因造血干细胞移植的结果在部分纠正的临床表现。我们推测，这些缺陷中的一些可以通过输注同种异体、多潜能、骨髓源性间充质干细胞（MSC）来纠正。对既往接受过HLA相同同胞成功骨髓移植的Hurler综合征（n = 5）或MLD（n = 6）患者输注2-10 × 10（6）/kg从原始供体骨髓穿刺液中分离和扩增的MSC。无输注相关毒性。在大多数受体中，MSC输注后2天、30-60天和6-24个月培养纯化的MSC仍然是宿主类型。在两名患者中，骨髓来源的MSC在MSC输注后60天通过FISH检测含有0.4%和2%的供体MSC。在4例MLD患者中，MSC输注后神经传导速度有显着改善。所有患者的骨密度保持不变或略有改善。MSC输注后，患者的整体健康、精神和身体发育没有临床明显变化。我们的结论是，供体同种异体MSC输注是安全的，并可能与逆转某些组织的疾病病理生理学。骨髓间充质干细胞在Hurler综合征和MLD治疗中的作用有待进一步评估。
Patients with Hurler syndrome (mucopolysaccharidosis type-IH) and metachromatic leukodystrophy (MLD) develop significant skeletal and neurologic defects that limit their survival. Transplantation of allogeneic hematopoietic stem cells results in partial correction of the clinical manifestations. We postulated that some of these defects may be corrected by infusion of allogeneic, multipotential, bone marrow-derived mesenchymal stem cells (MSC). Patients with Hurler syndrome (n = 5) or MLD (n = 6) who previously underwent successful bone marrow transplantation from an HLA-identical sibling were infused with 2-10 X 10(6)/kg MSCs, isolated and expanded from a bone marrow aspirate of the original donor. There was no infusion-related toxicity. In most recipients culture-purified MSCs at 2 days, 30-60 days and 6-24 months after MSC infusion remained of host type. In two patients the bone marrow-derived MSCs contained 0.4 and 2% donor MSCs by FISH 60 days after MSC infusion. In four patients with MLD there were significant improvements in nerve conduction velocities after MSC infusion. The bone mineral density was either maintained or slightly improved in all patients. There was no clinically apparent change in patients' overall health, mental and physical development after MSC infusion. We conclude that donor allogeneic MSC infusion is safe and may be associated with reversal of disease pathophysiology in some tissues. The role of MSCs in the management of Hurler syndrome and MLD should be further evaluated.