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ACS Appl Mater Interfaces. 2015 Nov 11;7(44):24629-40. doi: 10.1021/acsami.5b06804. Epub 2015 Nov 3.

A Neuroprotective Sericin Hydrogel As an Effective Neuronal Cell Carrier for the Repair of Ischemic Stroke.

Wang Z1,2, Wang J1, Jin Y3,4, Luo Z1, Yang W1, Xie H1, Huang K5, Wang L1,4,6.

Author information

1
Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
2
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
3
Department of Respiration, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, China 430022.
4
Medical Research Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China 430022.
5
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China 430022.
6
Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, China 430022.

Abstract

Ischemic stroke causes extensive cellular loss that impairs brain functions, resulting in severe disabilities. No effective treatments are currently available for brain tissue regeneration. The need to develop effective therapeutic approaches for treating stroke is compelling. A tissue engineering approach employing a hydrogel carrying both cells and neurotrophic cytokines to damaged regions is an encouraging alternative for neuronal repair. However, this approach is often challenged by low in vivo cell survival rate, and low encapsulation efficiency and loss of cytokines. To address these limitations, we propose to develop a biomaterial that can form a matrix capable of improving in vivo survival of transplanted cells and reducing in vivo loss of cytokines. Here, we report that using sericin, a natural protein from silk, we have fabricated a genipin-cross-linked sericin hydrogel (GSH) with porous structure and mild swelling ratio. The GSH supports the effective attachment and growth of neurons in vitro. Strikingly, our data reveal that sericin protein is intrinsically neurotrophic and neuroprotective, promoting axon extension and branching as well as preventing primary neurons from hypoxia-induced cell death. Notably, these functions are inherited by the GSH's degradation products, which might spare a need of incorporating costly cytokines. We further demonstrate that this neurotrophic effect is dependent on the Lkb1-Nuak1 pathway, while the neuroprotective effect is realized through regulating the Bcl-2/Bax protein ratio. Importantly, when transplanted in vivo, the GSH gives a high cell survival rate and allows the cells to continuously proliferate. Together, this work unmasks the neurotrophic and neuroprotective functions for sericin and provides strong evidence justifying the GSH's suitability as a potential neuronal cell delivery vehicle for ischemic stroke repair.

KEYWORDS:

hydrogel; neuronal cell carrier; neuroprotection; sericin; stroke

PMID:
26478947
DOI:
10.1021/acsami.5b06804
[Indexed for MEDLINE]

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