In Vivo Imaging of Allografted Glial-Restricted Progenitor Cell Survival and Hydrogel Scaffold Biodegradation.
In Vivo Imaging of Allografted Glial-Restricted Progenitor Cell Survival and Hydrogel Scaffold Biodegradation.
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同种异体移植的胶质限制性祖细胞存活和水凝胶支架生物降解的体内成像。
DOI：
10.1021/acsami.1c03415
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发表时间：
2021-05-26
影响因子：
9.5
通讯作者：
Bulte JWM
中科院分区：
文献类型：
--
作者：
Kuddannaya S;Zhu W;Chu C;Singh A;Walczak P;Bulte JWM
移植的胶质限制祖细胞(GRP)有可能局部替代已死亡的星形胶质细胞，并产生重新髓鞘的少突胶质细胞，以避免神经元死亡和功能障碍。然而，大多数中枢神经系统细胞治疗模式受到高初始细胞死亡和宿主抗移植物免疫反应的阻碍。我们发现，机械强度可调的复合透明质酸基水凝胶可以显著改善移植的玻璃纤维蛋白的存活和分化。将表达绿色荧光蛋白和萤火虫荧光素酶的同种异体GRP以优化的水凝胶配方支架植入免疫活性BALB/c小鼠脑内，然后进行体内生物发光成像和化学交换饱和转移磁共振成像(CEST MRI)。我们证明，明胶敏感的CEST MRI可以用于监测移植后5周内水凝胶支架的体内降解情况，而不需要外源性标记。在移植后第32天，GRPs水凝胶支架的移植细胞存活率是裸细胞的4.5倍。组织学分析显示，与裸细胞相比，支架细胞明显促进了细胞的增殖以及低聚2+和GFAP+细胞的分化，并降低了宿主的免疫反应性。因此，移植GRP的水凝胶支架结合细胞存活和水凝胶降解的一系列体内成像具有在神经胶质细胞治疗方面的进一步进展的潜力。
Transplanted glial-restricted progenitor (GRP) cells have potential to focally replace defunct astrocytes and produce remyelinating oligodendrocytes to avert neuronal death and dysfunction. However, most central nervous system cell therapeutic paradigms are hampered by high initial cell death and a host antigraft immune response. We show here that composite hyaluronic acid-based hydrogels of tunable mechanical strengths can significantly improve transplanted GRP survival and differentiation. Allogeneic GRPs expressing green fluorescent protein and firefly luciferase were scaffolded in optimized hydrogel formulations and transplanted intracerebrally into immunocompetent BALB/c mice followed by serial in vivo bioluminescent imaging and chemical exchange saturation transfer magnetic resonance imaging (CEST MRI). We demonstrate that gelatin-sensitive CEST MRI can be exploited to monitor hydrogel scaffold degradation in vivo for ~5 weeks post transplantation without necessitating exogenous labeling. Hydrogel scaffolding of GRPs resulted in a 4.5-fold increase in transplanted cell survival at day 32 post transplantation compared to naked cells. Histological analysis showed significant enhancement of cell proliferation as well as Olig2+ and GFAP+ cell differentiation for scaffolded cells compared to naked cells, with reduced host immunoreactivity. Hence, hydrogel scaffolding of transplanted GRPs in conjunction with serial in vivo imaging of cell survival and hydrogel degradation has potential for further advances in glial cell therapy.
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