Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury

Tiange Chen; Yuguo Xia; Liyang Zhang; Tao Xu; Yan Yi; Jianwei Chen; Ziyuan Liu; Liting Yang; Siming Chen; Xiaoxi Zhou; Xin Chen; Haiyu Wu; Jinfang Liu

doi:10.1016/j.mtbio.2023.100606

Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury

Mater Today Bio. 2023 Mar 8:19:100606. doi: 10.1016/j.mtbio.2023.100606. eCollection 2023 Apr.

Authors

Tiange Chen^{1

2

3}, Yuguo Xia^{1

2

3}, Liyang Zhang^{1

2

3}, Tao Xu⁴, Yan Yi^{2

5}, Jianwei Chen⁴, Ziyuan Liu^{1

2}, Liting Yang^{1

2

3}, Siming Chen^{1

2}, Xiaoxi Zhou^{1

2}, Xin Chen^{1

2}, Haiyu Wu^{1

2}, Jinfang Liu^{1

2}

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
³ Hypothalamic-Pituitary Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁴ Bio-Intelligent Manufacturing and Living Matter Bioprinting Center, Research Institute of Tsinghua University in Shenzhen, Tsinghua University, Shenzhen, China.
⁵ Reproductive Medicine Center, Xiangya Hospital, Central South University, Hunan, China.

Abstract

Neural stem cell (NSC) has gained considerable attention in traumatic brain injury (TBI) treatment because of their ability to replenish dysfunctional neurons and stimulate endogenous neurorestorative processes. However, their therapeutic effects are hindered by the low cell retention rate after transplantation into the dynamic brain. In this study, we found cerebrospinal fluid (CSF) flow after TBI is an important factor associated with cell loss following NSC transplantation. Recently, several studies have shown that hydrogels could serve as a beneficial carrier for stem cell transplantation, which provides a solution to prevent CSF flow-induced cell loss after TBI. For this purpose, we evaluated three different hydrogel scaffolds and found the gelatin methacrylate (GelMA)/sodium alginate (Alg) (GelMA/Alg) hydrogel scaffold showed the best capabilities for NSC adherence, growth, and differentiation. Additionally, we detected that pre-differentiated NSCs, which were loaded on the GelMA/Alg hydrogel and cultured for 7 days in neuronal differentiation medium (NSC [7d]), had the highest cell retention rate after CSF impact. Next, the neuroprotective effects of the NSC-loaded GelMA/Alg hydrogel scaffold were evaluated in a rat model of TBI. NSC [7d]-loaded GelMA/Alg markedly decreased microglial activation and neuronal death in the acute phase, reduced tissue loss, alleviated astrogliosis, promoted neurogenesis, and improved neurological recovery in the chronic phase. In summary, we demonstrated that the integration with the GelMA/Alg and modification of NSC differentiation could inhibit the influence of CSF flow on transplanted NSCs, leading to increased number of retained NSCs and improved neuroprotective effects, providing a promising alternative for TBI treatment.

Keywords: Cerebrospinal fluid flow; Hydrogel scaffold; Neural stem cells; Neuroprotection; Traumatic brain injury.