Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury

Kusano, Kazuo; Enomoto, Mitsuhiro; Hirai, Takashi; Tsoulfas, Pantelis; Sotome, Shinichi; Shinomiya, Kenichi; Okawa, Atsushi

doi:10.1016/j.bbrc.2010.02.088

Cited by 49 publications

(47 citation statements)

References 33 publications

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“…Trophic support appears to be the key to effective combination therapy. The secretion of neurotrophic factors can be stimulated in the injured spinal cord by neural stem cell transplantation or exercise training [20, 63, 64]. Combining these two therapies can significantly increase neurotrophic factor secretion.…”

Section: The Effect Of Combinatorial Strategy With Exercisementioning

confidence: 99%

Exercise Training Promotes Functional Recovery after Spinal Cord Injury

Wang

Deng

et al. 2016

Neural Plasticity

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The exercise training is an effective therapy for spinal cord injury which has been applied to clinic. Traditionally, the exercise training has been considered to improve spinal cord function only through enhancement, compensation, and replacement of the remaining function of nerve and muscle. Recently, accumulating evidences indicated that exercise training can improve the function in different levels from end-effector organ such as skeletal muscle to cerebral cortex through reshaping skeletal muscle structure and muscle fiber type, regulating physiological and metabolic function of motor neurons in the spinal cord and remodeling function of the cerebral cortex. We compiled published data collected in different animal models and clinical studies into a succinct review of the current state of knowledge.

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Section: The Effect Of Combinatorial Strategy With Exercisementioning

confidence: 99%

Exercise Training Promotes Functional Recovery after Spinal Cord Injury

Wang

Deng

et al. 2016

Neural Plasticity

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“…Transplantation of ASCs resulted in enhanced functional recovery of crushed motor and sensory fibers, most likely due to their ability to produce NTs and myelin precursor proteins, which act complementary to promote recovery (Lopatina et al, 2011). Another study reported that the transplantation of neural stem cells (NSCs) expressing NT3/D15A (a multi NT with the capacity to bind both TrkC and TrkB) enhanced partial hindlimb recovery and myelination in the chronic phase of spinal cord injury (Kusano et al, 2010). These studies suggest that functional recovery by NTs could be mediated by a dual mechanism supporting both axonal regeneration and remyelination.…”

Section: Nt Treatment Increase Regeneration After Spinal Cord Injury mentioning

confidence: 99%

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Kelamangalath

Smith

2013

Front. Biol.

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Neurotrophins are a family of growth factors that have been found to be central for the development and functional maintenance of the nervous system, participating in neurogenesis, neuronal survival, axonal growth, synaptogenesis and activity-dependent forms of synaptic plasticity. Trauma in the adult nervous system can disrupt the functional circuitry of neurons and result in severe functional deficits. The limitation of intrinsic growth capacity of adult nervous system and the presence of an inhospitable environment are the major hurdles for axonal regeneration of lesioned adult neurons. Neurotrophic factors have been shown to be excellent candidates in mediating neuronal repair and establishing functional circuitry via activating several growth signaling mechanisms including neuron-intrinsic regenerative programs. Here, we will review the effects of various neurotrophins in mediating recovery after injury to the adult spinal cord.

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“…A possible reason for this may be that oligodendrocytes undergo apoptosis, and although spontaneous remyelination occurs, endogenous OPCs supply is limited and inadequate for functional improvement. NT-3 overexpressing SCs significantly improve remyelination by which NT-3 recruits OPCs [34,40]. It is suggested that SCs may play a critical role as myelinogenic cells to facilitate axon regeneration, act as a bridge, support axonal outgrowth, and finally ensheath axons to mediate functional recovery [41,42].…”

Section: Discussionmentioning

confidence: 99%

Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

Lai

Wang²,

Ling³

et al. 2014

Stem Cells and Development

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Remyelination remains a challenging issue in spinal cord injury (SCI). In the present study, we cocultured Schwann cells (SCs) and neural stem cells (NSCs) with overexpression of neurotrophin-3 (NT-3) and its high affinity receptor tyrosine kinase receptor type 3 (TrkC), respectively, in a gelatin sponge (GS) scaffold. This was aimed to generate a tissue-engineered neural scaffold and to investigate whether it could enhance myelination after a complete T10 spinal cord transection in adult rats. Indeed, many NT-3 overexpressing SCs (NT-3-SCs) in the GS scaffold assumed the formation of myelin. More strikingly, a higher incidence of NSCs overexpressing TrkC differentiating toward myelinating cells was induced by NT-3-SCs. By transmission electron microscopy, the myelin sheath showed distinct multilayered lamellae formed by the seeded cells. Eighth week after the scaffold was transplanted, some myelin basic protein (MBP)-positive processes were observed within the transplantation area. Remarkably, certain segments of myelin derived from NSC-derived myelinating cells and NT-3-SCs were found to ensheath axons. In conclusion, we show here that transplantation of the GS scaffold promotes exogenous NSC-derived myelinating cells and SCs to form myelins in the injury/transplantation area of spinal cord. These findings thus provide a neurohistological basis for the future application or transplantation using GS neural scaffold to repair SCI.

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Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury

Cited by 49 publications

References 33 publications

Exercise Training Promotes Functional Recovery after Spinal Cord Injury

Exercise Training Promotes Functional Recovery after Spinal Cord Injury

Neurotrophin treatment to promote regeneration after traumatic CNS injury

Graft of a Tissue-Engineered Neural Scaffold Serves as a Promising Strategy to Restore Myelination after Rat Spinal Cord Transection

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