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Designer, injectable gels to prevent transplanted Schwann cell loss during spinal cord injury therapy
Science Advances ( IF 11.7 ) Pub Date : 2020-04-01 , DOI: 10.1126/sciadv.aaz1039
Laura M. Marquardt 1, 2 , Vanessa M. Doulames 2 , Alice T. Wang 1 , Karen Dubbin 1 , Riley A. Suhar 1 , Michael J. Kratochvil 1, 3 , Zachary A. Medress 2 , Giles W. Plant 2 , Sarah C. Heilshorn 1
Affiliation  

Transplantation of patient-derived Schwann cells is a promising regenerative medicine therapy for spinal cord injuries; however, therapeutic efficacy is compromised by inefficient cell delivery. We present a materials-based strategy that addresses three common causes of transplanted cell death: (i) membrane damage during injection, (ii) cell leakage from the injection site, and (iii) apoptosis due to loss of endogenous matrix. Using protein engineering and peptide-based assembly, we designed injectable hydrogels with modular cell-adhesive and mechanical properties. In a cervical contusion model, our hydrogel matrix resulted in a greater than 700% improvement in successful Schwann cell transplantation. The combination therapy of cells and gel significantly improved the spatial distribution of transplanted cells within the endogenous tissue. A reduction in cystic cavitation and neuronal loss were also observed with substantial increases in forelimb strength and coordination. Using an injectable hydrogel matrix, therefore, can markedly improve the outcomes of cellular transplantation therapies.



中文翻译:

设计者,可注射的凝胶可防止脊髓损伤治疗期间移植的雪旺氏细胞丢失

患者源性雪旺细胞的移植是一种有希望的脊髓损伤再生医学疗法。然而,无效的细胞递送损害了治疗功效。我们提出了一种基于材料的策略,该策略解决了移植细胞死亡的三种常见原因:(i)注射过程中的膜损伤,(ii)注射部位的细胞渗漏和(iii)由于内源性基质的丧失而导致的细胞凋亡。使用蛋白质工程和基于肽的组装,我们设计了具有模块化细胞粘附和机械性能的可注射水凝胶。在宫颈挫伤模型中,我们的水凝胶基质在成功的Schwann细胞移植中带来了超过700%的改善。细胞和凝胶的联合治疗显着改善了内源性组织内移植细胞的空间分布。还观察到囊泡空化和神经元丢失的减少,前肢力量和协调能力的显着提高。因此,使用可注射的水凝胶基质可以显着改善细胞移植治疗的效果。

更新日期:2020-04-01
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