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过表达神经营养因子 3 的间充质干细胞移植可促进大鼠完全性脊髓横断后运动功能的改善,而不伴有轴突再生。

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

机构信息

Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI 48859, USA; Program in Neurosciences, Central Michigan University, Mount Pleasant, MI 48859, USA.

Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mount Pleasant, MI 48859, USA; Program in Neurosciences, Central Michigan University, Mount Pleasant, MI 48859, USA; Department of Psychology, Central Michigan University, Mount Pleasant, MI 48859, USA; College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA.

出版信息

Brain Res. 2018 Nov 15;1699:19-33. doi: 10.1016/j.brainres.2018.06.002. Epub 2018 Jun 5.


DOI:10.1016/j.brainres.2018.06.002
PMID:29883625
Abstract

Transplanting stem cells engineered to overexpress trophic factors can improve motor abilities and facilitate axon regeneration following spinal cord injury. This study compared several transplantation paradigms using mesenchymal stem cells (MSCs) that overexpress the multi-neurotrophin, NT-3/D15A (NT-3-MSCs), to determine if different grafting strategies can elicit improved axon regeneration and/or behavioral outcomes following a complete T9 spinal transection. At one week post-transection, NT-3-MSCs were transplanted above, and at several locations below, the lesion site. A rostral-to-caudal gradient of NT-3-MSCs was produced by incrementally increasing the number of transplanted cells at locations distal to the transection. Motor function was analyzed using the Basso, Beattie, and Bresnahan scale for 7-weeks post-injury. The corticospinal tract was traced using biotinylated dextran amines, while raphespinal fibers were visualized using immunohistochemistry. Cell viability was assessed using transplants of NT-3-MSCs that express tdTomato. Retrograde tracing using fluorogold, as well as spinal re-transections, were performed to discriminate between a supra-spinal or reflexive influence of regained motor functions. NT-3-MSC transplants improved motor outcomes and tissue continuity at the transection site, however retrograde tracing using fluorogold revealed no evidence of axon regeneration. A spinal re-transection also failed to eliminate the improvement in motor outcomes produced by the transplant. We conclude that transplantation of NT-3-MSCs can improve motor function and morphological outcomes following a complete spinal transection without promoting axonal regeneration.

摘要

移植过表达神经营养因子的干细胞可以改善脊髓损伤后的运动能力并促进轴突再生。本研究比较了几种使用过表达多神经营养因子 NT-3/D15A(NT-3-MSCs)的间充质干细胞(MSCs)的移植范例,以确定不同的移植策略是否可以在完全 T9 脊髓横断后引起更好的轴突再生和/或行为结果。在横断后一周,将 NT-3-MSCs 移植到损伤部位上方和下方的多个部位。通过在远离横断部位的位置逐渐增加移植细胞的数量,产生了从头部到尾部的 NT-3-MSCs 梯度。在损伤后 7 周使用 Basso、Beattie 和 Bresnahan 量表分析运动功能。使用生物素化葡聚糖胺追踪皮质脊髓束,并用免疫组织化学观察中缝脊髓纤维。使用表达 tdTomato 的 NT-3-MSC 移植评估细胞活力。使用荧光金进行逆行追踪,以及对脊髓进行再横切,以区分恢复运动功能的是上运动神经元或反射性影响。NT-3-MSC 移植改善了运动结果和损伤部位的组织连续性,但使用荧光金进行逆行追踪没有发现轴突再生的证据。脊髓再横切也未能消除移植产生的运动结果改善。我们得出结论,移植 NT-3-MSCs 可以改善完全脊髓横断后的运动功能和形态结果,而不会促进轴突再生。

相似文献

[1]
Transplantation of mesenchymal stem cells that overexpress NT-3 produce motor improvements without axonal regeneration following complete spinal cord transections in rats.

Brain Res. 2018-6-5

[2]
SDF-1 overexpression by mesenchymal stem cells enhances GAP-43-positive axonal growth following spinal cord injury.

Restor Neurol Neurosci. 2017

[3]
Matrix inclusion within synthetic hydrogel guidance channels improves specific supraspinal and local axonal regeneration after complete spinal cord transection.

Biomaterials. 2006-1

[4]
Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells overexpressing TrkC into neuron-like cells in transected spinal cord of rats.

Cell Transplant. 2012-9-21

[5]
Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection.

Stem Cell Res Ther. 2015-5-27

[6]
Electro-acupuncture promotes differentiation of mesenchymal stem cells, regeneration of nerve fibers and partial functional recovery after spinal cord injury.

Exp Toxicol Pathol. 2011-1

[7]
Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord.

Brain Res. 2010-9-29

[8]
Bone marrow mesenchymal stem cells and electroacupuncture downregulate the inhibitor molecules and promote the axonal regeneration in the transected spinal cord of rats.

Cell Transplant. 2010-9-30

[9]
Transplantation of neurotrophin-3-expressing bone mesenchymal stem cells improves recovery in a rat model of spinal cord injury.

Acta Neurochir (Wien). 2014-7

[10]
Transplants and neurotrophic factors increase regeneration and recovery of function after spinal cord injury.

Prog Brain Res. 2002

引用本文的文献

[1]
Dimethyl Fumarate Preconditioning can Reinforce the Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells through Trophic Factor Profile Enhancement.

Adv Biomed Res. 2024-7-29

[2]
Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta‑analysis.

Neurosurg Rev. 2024-2-19

[3]
Prospects for the use of olfactory mucosa cells in bioprinting for the treatment of spinal cord injuries.

World J Clin Cases. 2023-1-16

[4]
Mesenchymal stem cells for regenerative medicine in central nervous system.

Front Neurosci. 2022-12-13

[5]
Sustained delivery of neurotrophic factors to treat spinal cord injury.

Transl Neurosci. 2021-11-30

[6]
Stem Cell Therapy for Spinal Cord Injury.

Cell Transplant. 2021

[7]
In vivo conversion of rat astrocytes into neuronal cells through neural stem cells in injured spinal cord with a single zinc-finger transcription factor.

Stem Cell Res Ther. 2019-12-16

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