The survival of engrafted neural stem cells within hyaluronic acid hydrogels.

The survival of engrafted neural stem cells within hyaluronic acid hydrogels.
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DOI:
10.1016/j.biomaterials.2013.03.095
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发表时间:
2013-07
期刊:
影响因子:
14
通讯作者:
Bulte, Jeff W. M.
Bulte, Jeff W. M.
中科院分区:
工程技术1区
文献类型:
--
作者:
Liang, Yajie;Walczak, Piotr;Bulte, Jeff W. M.

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神经系统疾病的成功细胞治疗高度依赖于移植干细胞的存活,而裸的、未受保护的细胞的总体移植存活率通常仍然很差。我们研究了使用可注射的透明质酸(HA)水凝胶来增强移植的小鼠C17.2细胞、人神经祖细胞(ReNcells)和人胶质限制性前体(GRP)的存活。HA水凝胶的凝胶化性质首先被表征并优化用于脑内注射,导致水凝胶组分混合后延迟注射25分钟。使用生物发光成像(BLI)作为细胞存活的非侵入性读出,我们发现水凝胶可以保护异种移植的细胞,如植入免疫活性大鼠中的C17.2细胞的延长存活所证明的(在第12天p<0.01)。植入免疫活性或免疫缺陷小鼠脑中的人ReN细胞和人GRP的存活在水凝胶支架后也显著改善(ReN细胞,第5天p<0.05; GRP,第7天p<0.05)。然而,在将水凝胶注射到免疫活性小鼠脑中后两周可注意到炎症反应。我们得出结论,水凝胶支架增加移植的神经干细胞的存活,证明进一步优化水凝胶组合物。
Successful cell-based therapy of neurological disorders is highly dependent on the survival of transplanted stem cells, with the overall graft survival of naked, unprotected cells in general remaining poor. We investigated the use of an injectable hyaluronic acid (HA) hydrogel for enhancement of survival of transplanted mouse C17.2 cells, human neural progenitor cells (ReNcells), and human glial-restricted precursors (GRPs). The gelation properties of the HA hydrogel were first characterized and optimized for intracerebral injection, resulting in a 25 min delayed-injection after mixing of the hydrogel components. Using bioluminescence imaging (BLI) as a non-invasive readout of cell survival, we found that the hydrogel can protect xenografted cells as evidenced by the prolonged survival of C17.2 cells implanted in immunocompetent rats (p<0.01 at day 12). The survival of human ReNcells and human GRPs implanted in the brain of immunocompetent or immunodeficient mice was also significantly improved after hydrogel scaffolding (ReNcells, p<0.05 at day 5; GRPs, p<0.05 at day 7). However, an inflammatory response could be noted two weeks after injection of hydrogel into immunocompetent mice brains. We conclude that hydrogel scaffolding increases the survival of engrafted neural stem cells, justifying further optimization of hydrogel compositions.
在两个人类神经干细胞系中神经元生理反应性的差异发展。
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