Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury

doi:10.1007/s11684-018-0642-z

Front. Med.

2019, Vol. 13

Issue (2) : 131-137 https://doi.org/10.1007/s11684-018-0642-z

REVIEW

Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury

Bin Yu, Xiaosong Gu(

)

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China

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Abstract

The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To circumvent these barriers, biomaterial scaffolds are applied to bridge the lesion gaps for the regrowing axons to follow, and, often by combining stem cell transplantation, to enable the local environment in the growth-supportive direction. Manipulations, such as the modulation of PTEN/mTOR pathways, can also enhance intrinsic CNS axon regrowth after injury. Given the complex pathophysiology of SCI, combining biomaterial scaffolds and genetic manipulation may provide synergistic effects and promote maximal axonal regrowth. Future directions will primarily focus on the translatability of these approaches and promote therapeutic avenues toward the functional rehabilitation of patients with SCIs.

Keywords spinal cord injury biomaterial extrinsic barrier intrinsic regeneration capacity

Corresponding Author(s): Xiaosong Gu

Just Accepted Date: 25 July 2018 Online First Date: 31 August 2018 Issue Date: 28 March 2019

Cite this article:

Bin Yu,Xiaosong Gu. Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury[J]. Front. Med., 2019, 13(2): 131-137.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0642-z
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I2/131

Fig.1 Combinational strategies to enhance axon regrowth and functional recovery after SCI. CNS neurons switch from robust growth state to relatively static state during development, marked by expressional changes of key molecules and signaling pathways. After CNS injury, extrinsically, myelin-associated inhibitors (Nogo-A, MAG, OMgp), CSPGs, and glia scar/cavity create a high-growth impermissive environment. Successful axon regeneration is therefore impeded by intrinsic and extrinsic factors. By employing a biomaterial matrix that bridges the lesion site, providing growth-permissive environment by stem cells, or engineering the cell transplantation, the enhancement of axon regeneration induced by manipulation of cell autonomous growth capacity can synergistically boost and achieve significant functional recovery.

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