Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation
Analysis of Tissues Following Mesenchymal Stromal Cell Therapy in Humans Indicates Limited Long-Term Engraftment and No Ectopic Tissue Formation
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DOI：
10.1002/stem.1118
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发表时间：
2012-07-01
期刊：
影响因子：
5.2
通讯作者：
Le Blanc, K.
中科院分区：
文献类型：
--
作者：
von Bahr, L.;Batsis, I.;Le Blanc, K.
间充质基质细胞（MSC）被探索作为一种新的治疗各种医疗条件。它们在输注后的命运尚不清楚，并且尚未在患者中讨论关于恶性转化和异位组织形成的长期安全性。我们检查了18例接受人类白细胞抗原（HLA）不匹配的MSC的患者的尸检材料，并对15例患者的108份组织样本进行了PCR检测。肉眼或组织学检查未发现异位组织形成或MSC供体来源的恶性肿瘤的迹象。在8名患者的一个或多个组织（包括肺、淋巴结和肠）中检测到MSC供体DNA，水平为1/100至< 1/1，000。MSC供体DNA的检测与从输注到样本收集的时间呈负相关，因为在采样前50天内给予的13次MSC输注中有9次检测到DNA，但在之前给予的8次输注中只有2次检测到DNA。MSC植入和治疗反应之间没有相关性。我们的结论是，骨髓间充质干细胞似乎通过“打了就跑”的机制来介导其功能。缺乏持续的植入限制了MSC治疗的长期风险。干细胞2012;30：1575-1578
Mesenchymal stromal cells (MSCs) are explored as a novel treatment for a variety of medical conditions. Their fate after infusion is unclear, and long-term safety regarding malignant transformation and ectopic tissue formation has not been addressed in patients. We examined autopsy material from 18 patients who had received human leukocyte antigen (HLA)-mismatched MSCs, and 108 tissue samples from 15 patients were examined by PCR. No signs of ectopic tissue formation or malignant tumors of MSC-donor origin were found on macroscopic or histological examination. MSC donor DNA was detected in one or several tissues including lungs, lymph nodes, and intestine in eight patients at levels from 1/100 to < 1/1,000. Detection of MSC donor DNA was negatively correlated with time from infusion to sample collection, as DNA was detected from nine of 13 MSC infusions given within 50 days before sampling but from only two of eight infusions given earlier. There was no correlation between MSC engraftment and treatment response. We conclude that MSCs appear to mediate their function through a "hit and run" mechanism. The lack of sustained engraftment limits the long-term risks of MSC therapy. STEM CELLS 2012;30:1575-1578