Encapsulated mesenchymal stromal cells for in vivo transplantation.
Encapsulated mesenchymal stromal cells for in vivo transplantation.
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DOI：
10.1002/bit.23233
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发表时间：
2011-11
影响因子：
3.8
通讯作者：
Yarmush, Martin L.
中科院分区：
文献类型：
--
作者：
Barminko, Jeffrey;Kim, Jae Hwan;Otsuka, Seiji;Gray, Andrea;Schloss, Rene;Grumet, Martin;Yarmush, Martin L.
关键词：
免疫调节性人间充质基质细胞(HMSC)已被纳入治疗方案，用于治疗动物模型脊髓损伤(SCI)后的继发性炎症反应。然而，hMSC直接植入方法的局限性可能会阻碍将hMSC输注的治疗进展有效地转化为脊髓损伤后的治疗方案。为了绕过这些限制，我们研究了藻酸盐微胶囊在开发hMSC可植入载体方面的有效性。包裹的人骨髓间充质干细胞的活性和分泌功能保持不变，在促炎因子肿瘤坏死因子-α和干扰素-γ的诱导下，人骨髓间充质干细胞分泌抗炎细胞因子。此外，包裹的hMSC在体外和体内都能调节炎症巨噬细胞的功能，即使在没有hMSC与巨噬细胞直接接触的情况下也是如此，并促进了另一种M2巨噬细胞表型。在体外，这一点很明显，巨噬细胞iNOS表达减少，伴随而来的是M2巨噬细胞标志物CD206的增加。最后，采用体重下降模型(NYU模型)致伤SD大鼠T10椎体脊髓，伤后24小时腰椎穿刺置入包裹的hMSC。包裹的人骨髓间充质干细胞主要定位于脊髓的马尾。脊髓损伤后7天脊髓组织的组织学评估表明，仅5×104个包裹的hMSC就能产生更多表达CD206的巨噬细胞，这与我们的体外研究一致。综合研究结果支持将固定化的hMSC纳入中枢神经系统损伤后的组织保护治疗，并表明巨噬细胞向M2亚群的转化至少在一定程度上对组织保护负责。
Immunomodulatory human mesenchymal stromal cells (hMSC) have been incorporated into therapeutic protocols to treat secondary inflammatory responses post-spinal cord injury (SCI) in animal models. However, limitations with direct hMSC implantation approaches may prevent effective translation for therapeutic development of hMSC infusion into post-SCI treatment protocols. To circumvent these limitations, we investigated the efficacy of alginate microencapsulation in developing an implantable vehicle for hMSC delivery. Viability and secretory function were maintained within the encapsulated hMSC population, and hMSC secreted anti-inflammatory cytokines upon induction with the pro-inflammatory factors, TNF-α and IFN-γ. Furthermore, encapsulated hMSC modulated inflammatory macrophage function both in-vitro and in-vivo, even in the absence of direct hMSC-macrophage cell contact and promoted the alternative M2 macrophage phenotype. In-vitro, this was evident by a reduction in macrophage iNOS expression with a concomitant increase in CD206, a marker for M2 macrophages. Finally, Sprague-Dawley rat spinal cords were injured at vertebra T10 via a weight drop model (NYU model) and encapsulated hMSC were administered via lumbar puncture 24 hours post- injury. Encapsulated hMSC localized primarily in the cauda equina of the spinal cord. Histological assessment of spinal cord tissue 7 days post SCI indicated that as few as 5×104 encapsulated hMSC yielded increased numbers of CD206-expressing macrophages, consistent with our in-vitro studies. The combined findings support the inclusion of immobilized hMSC in post-CNS trauma tissue protective therapy, and suggest that conversion of macrophages to the M2 subset is responsible, at least in part, for tissue protection.
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影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
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：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Langrana, Noshir A.
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
DOI：
10.1073/pnas.1008117107
发表时间：
2010-08-03
影响因子：
11.1
作者：
Bartosh, Thomas J.;Ylostalo, Joni H.;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.