Transplantation of mesenchymal stem cells that overexpress NT-3 produce motor improvements without axonal regeneration following complete spinal cord transections in rats

Stewart, Andrew N.; Kendziorski, Griffin; Deak, Zachary M.; Bartosek, Nathanial C.; Rezmer, Brooke E.; Jenrow, Kenneth A.; Rossignol, Julien; Dunbar, Gary

doi:10.1016/j.brainres.2018.06.002

Cited by 15 publications

(9 citation statements)

References 70 publications

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“…IGF-1 overexpression of BM-MSCs strengthens antioxidant reactions and improves basso mouse scale (BMS) scores 65 . Other approaches, such as modification of the microRNA-124 gene 66 , silencing the Nogo-66 receptor gene 67 , inhibition of tumor necrosis factor α (TNF-α) 68 , and overexpression of neurotrophin-3 (NT-3) 69 , the chemokine stromal-derived factor-1 70 , and neurotrophic factor-derived glial cell (GDNF) genes 71 , exhibited better efficacy than original BM-MSCs in motor function and surrounding axon densities. The effects of individual cell transplantation are enhanced by cotransplantation with cells from other sources.…”

Section: Stem Cell Transplantation Strategymentioning

confidence: 99%

Stem Cell Therapy for Spinal Cord Injury

Huang

Xiong

et al. 2021

Cell Transplant

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Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

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Section: Stem Cell Transplantation Strategymentioning

confidence: 99%

Stem Cell Therapy for Spinal Cord Injury

Huang

Xiong

et al. 2021

Cell Transplant

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“…33,34 The MSCs, as a kind of stem cells with self-renewal and differentiation capabilities, could secrete varies kind of neural growth factors for the nerve fiber regeneration. 43,44 In this work, the MSCladen microfibers not only improved the host neuron immigration into the lesion site, but also promoted the neural differentiation of donor MSCs.…”

Section: Discussionmentioning

confidence: 84%

“…The MSCs cultured on the fibrin hydrogel fibers could “feel” the topography and stiffness of the matrix and are induced to long spindle spreading and then tend to neural differentiation . Furthermore, the implantation of AFG in the SCI lesion site could rapidly induce the host cell invasion and form aligned tissue cables to bridge the injury gap, and then the nerve fibers could regenerate along the tissue cables from the caudal or rostral site to the middle site. , The MSCs, as a kind of stem cells with self-renewal and differentiation capabilities, could secrete varies kind of neural growth factors for the nerve fiber regeneration. , In this work, the MSC-laden microfibers not only improved the host neuron immigration into the lesion site, but also promoted the neural differentiation of donor MSCs.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cell-Laden Hydrogel Microfibers for Promoting Nerve Fiber Regeneration in Long-Distance Spinal Cord Transection Injury

Yao

Cao

et al. 2020

ACS Biomater. Sci. Eng.

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Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). However, low survival rate, uncontrollable migration, and differentiation of stem cells after implantation represent major challenges toward the clinical deployment of this approach. In this study, we fabricated three-dimensional MSC-laden microfibers via electrospinning in a rotating cell culture to mimic nerve tissue, control stem cell behavior, and promote integration with the host tissue. The hierarchically aligned fibrin hydrogel was used as the MSC carrier though a rotating method and the aligned fiber structure induced the MSC-aligned adhesion on the surface of the hydrogel to form microscale cell fibers. The MSC-laden microfiber implantation enhanced the donor MSC neural differentiation, encouraged the migration of host neurons into the injury gap and significantly promoted nerve fiber regeneration across the injury site. Abundant GAP-43- and NF-positive nerve fibers were observed to regenerate in the caudal, rostral, and middle sites of the injury position 8 weeks after the surgery. The NF fiber density reached to 29 ± 6 per 0.25 mm2 at the middle site, 82 ± 13 per 0.25 mm2 at the adjacent caudal site, and 70 ± 23 at the adjacent rostral site. Similarly, motor axons labeled with 5-hydroxytryptamine were significantly regenerated in the injury gap, which was 122 ± 22 at the middle injury site that was beneficial for motor function recovery. Most remarkably, the transplantation of MSC-laden microfibers significantly improved electrophysiological expression and re-established limb motor function. These findings highlight the combination of MSCs with microhydrogel fibers, the use of which may become a promising method for MSC implantation and SCI repair.

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“…Transgenic stem cells can not only improve the ability of cells to differentiate, but also express a large number of specific neurotrophic factors and reconstruct the spinal nerve circuit [50]. Many animal SCI model studies combined with gene therapy, such as NT-3 over-secreting BM-SCs [51] and hUCB-MSCs [52], CSF-induced BM-SCs [53], Schwann-like cells after BM-SCs being induced by sciatic nerve fragments [54], etc. They have all been proved to be better than simply transplanting cell in promoting functional recovery.…”

Section: Cell Transplantation Combined With Gene Therapymentioning

confidence: 99%

The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury

Zhang

Wang

Song

2019

Journal of Neurorestoratology

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Through retrospective analysis of the literature on the cell repair of spinal cord injury worldwide, it is found that the mechanism of cell transplantation repairing spinal cord injury is mainly to replace damaged neurons, protect host neurons, prevent apoptosis, promote axonal regeneration and synapse formation, promote myelination, and secrete trophic factors or growth factors to improve microenvironment. A variety of cells are used to repair spinal cord injury. Stem cells include multipotent stem cells, embryonic stem cells, and induced pluripotent stem cells. The multipotent stem cells are mainly various types of mesenchymal stem cells and neural stem cells. Non-stem cells include olfactory ensheathing cells and Schwann cells. Transplantation of inhibitory interneurons to alleviate neuropathic pain in patients is receiving widespread attention. Different types of cell transplantation have their own advantages and disadvantages, and multiple cell transplantation may be more helpful to the patient’s functional recovery. These cells have certain effects on the recovery of neurological function and the improvement of complications, but further exploration is needed in clinical application. The application of a variety of cell transplantation, gene technology, bioengineering and other technologies has made the prospect of cell transplantation more extensive. There is a need to find a safe and effective comprehensive treatment to maximize and restore the patient’s performance.

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Transplantation of mesenchymal stem cells that overexpress NT-3 produce motor improvements without axonal regeneration following complete spinal cord transections in rats

Cited by 15 publications

References 70 publications

Stem Cell Therapy for Spinal Cord Injury

Stem Cell Therapy for Spinal Cord Injury

Mesenchymal Stem Cell-Laden Hydrogel Microfibers for Promoting Nerve Fiber Regeneration in Long-Distance Spinal Cord Transection Injury

The cell repair research of spinal cord injury: a review of cell transplantation to treat spinal cord injury

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