Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection

Zeng, Xiang; Qiu, Xuecheng; Ma, Yuan-Huan; Duan, Jingjing; Chen, Yong; Gu, Huaiyu; Wang, Junmei; Ling, Eng‐Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

doi:10.1016/j.biomaterials.2015.02.073

Cited by 94 publications

(92 citation statements)

References 73 publications

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“…Buoyed by the success in constructing functional neural networks from adult stem cells in vitro to repair SCI in our previous studies,11, 18 the present study has constructed a SCLT simulating the major cellular composition of the gray matter as well as the white matter of the spinal cord. When transplanted into the injured spinal cord, the SCLT integrated with the host tissue and exhibited targeted repair to the gray and white matter damage after injury.…”

Section: Discussionmentioning

confidence: 99%

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

et al. 2018

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Tissue engineering–based neural construction holds promise in providing organoids with defined differentiation and therapeutic potentials. Here, a bioengineered transplantable spinal cord–like tissue (SCLT) is assembled in vitro by simulating the white matter and gray matter composition of the spinal cord using neural stem cell–based tissue engineering technique. Whether the organoid would execute targeted repair in injured spinal cord is evaluated. The integrated SCLT, assembled by white matter–like tissue (WMLT) module and gray matter–like tissue (GMLT) module, shares architectural, phenotypic, and functional similarities to the adult rat spinal cord. Organotypic coculturing with the dorsal root ganglion or muscle cells shows that the SCLT embraces spinal cord organogenesis potentials to establish connections with the targets, respectively. Transplantation of the SCLT into the transected spinal cord results in a significant motor function recovery of the paralyzed hind limbs in rats. Additionally, targeted spinal cord tissue repair is achieved by the modular design of SCLT, as evidenced by an increased remyelination in the WMLT area and an enlarged innervation in the GMLT area. More importantly, the pro‐regeneration milieu facilitates the formation of a neuronal relay by the donor neurons, allowing the conduction of descending and ascending neural inputs.

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Section: Discussionmentioning

confidence: 99%

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

et al. 2018

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“…In accordance with our previous work,12 we have provided here with further evidence that supports the use of bioactive scaffold to reform central pattern‐generating circuitry of spinal interneurons in canines. Similar to using genetically engineered to delivery NT‐3,11 bioactive scaffolds are evidently beneficial to improve post‐injury environment and to circumvent the risk of virus transmission. More importantly, this strategy has alluring prospect of clinical application for spinal cord injury.…”

Section: Discussionmentioning

confidence: 99%

“…Schwann cells overexpressing NT‐3 could provide sufficient nutrition for constituting an adult stem cell‐derived neural network in vitro 11. This had prompted us to design a novel bioactive scaffold for the delivery of NT‐3 by using the NT‐3/fibroin particles as surface decoration.…”

Section: Introductionmentioning

confidence: 99%

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

Che

Zeng

et al. 2018

J Biomedical Materials Res

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Spinal cord injury (SCI) normally results in cell death, scarring, cavitation, inhibitory molecules release, etc., which are regarded as a huge obstacle to reconnect the injured neuronal circuits because of the lack of effective stimulus. In this study, a functional gelatin sponge scaffold was used to inhibit local inflammation, enhance nerve fiber regeneration, and improve neural conduction in the canine. This scaffold had good porosity and modified with neurotrophin‐3 (NT‐3)/fibroin complex, which showed sustained release in vitro. After the scaffold was transplanted into canine spinal cord hemisection model, hindlimb movement, and neural conduction were improved evidently. Migrating host cells, newly formed neurons with associated synaptic structures together with functional blood vessels with intact endothelium in the regenerating tissue were identified. Taken together, the results demonstrated that using bioactive scaffold could establish effective microenvironment stimuli for endogenous regeneration, providing a potential and practical strategy for treatment of spinal cord injury. © 2018 The Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2158‐2170, 2018.

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“…With the opinion that bone marrow derived Mesenchymal Stem Cells (MSCs) could benefit spinal cord regeneration because of their neuroprotection and postinjury microenvironment modulating abilities, neuronal induced MSCs were encapsulated into 3D gelatin sponge scaffolds and then implanted into rat models with fully transected injury at T10 segments. Eight weeks after transplantation, the MSC-derived neuron-like cells maintained their synapse-like morphology in vivo and further formed connections with host neurites; the hind limb function of the treated rats was significantly improved, and the cortical motor evoked potential (CMEP) was also significantly recovered [24]. In other similar studies, NSCs plus gelatin treated group showed highest expression of laminin (a pro-neurogenic molecule) and decreased chondroitin sulfate proteoglycans which inhibit the axonal growth and neuroplasticity.…”

Section: Gelatinmentioning

confidence: 95%

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

Niu¹,

Zeng²

2015

J Tissue Sci Eng

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Spinal Cord Injury (SCI) results in the permanent functional impairment, leading to monoplegia, paraplegia or tetraplegia with tremendous social and economic burden. The intrinsic repair mechanism has been proven to be insufficient. The complex pathophysiology after injury imposes enormous challenging to functional recovery, given the most advanced medical intervention nowadays. Therefore, the development of effective therapeutic strategy for spinal cord injury management is in great need. Here we review a stem cell based tissue engineering approach under preclinical or clinical development for spinal cord injury, with a focus on promoting functional recovery after SCI, aiming to provide some beneficial suggestion on stem cell based tissue engineering design.

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Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection

Cited by 94 publications

References 73 publications

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

A Modular Assembly of Spinal Cord–Like Tissue Allows Targeted Tissue Repair in the Transected Spinal Cord

Neurotrophin‐3 released from implant of tissue‐engineered fibroin scaffolds inhibits inflammation, enhances nerve fiber regeneration, and improves motor function in canine spinal cord injury

The Application of Stem Cell Based Tissue Engineering in Spinal Cord Injury Repair.

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