Cell Transplantation Therapies for Spinal Cord Injury Focusing on Bone Marrow Mesenchymal Stem Cells: Advances and Challenges

Overview

Journal World J Stem Cells

Publisher Baishideng Publishing Group

Date 2023 Jun 21

PMID 37342219

Authors

Li-Yi Huang

Xin Sun

Hong-Xia Pan

Lu Wang

Cheng-Qi He

Quan Wei

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) is a devastating condition with complex pathological mechanisms that lead to sensory, motor, and autonomic dysfunction below the site of injury. To date, no effective therapy is available for the treatment of SCI. Recently, bone marrow-derived mesenchymal stem cells (BMMSCs) have been considered to be the most promising source for cellular therapies following SCI. The objective of the present review is to summarize the most recent insights into the cellular and molecular mechanism using BMMSC therapy to treat SCI. In this work, we review the specific mechanism of BMMSCs in SCI repair mainly from the following aspects: Neuroprotection, axon sprouting and/or regeneration, myelin regeneration, inhibitory microenvironments, glial scar formation, immunomodulation, and angiogenesis. Additionally, we summarize the latest evidence on the application of BMMSCs in clinical trials and further discuss the challenges and future directions for stem cell therapy in SCI models.

Citing Articles

Bone marrow mesenchymal stem cells modulate miR-202-3p to suppress neuronal apoptosis following spinal cord injury through autophagy activation via the AMPK, MAPK, and PI3K/AKT/mTOR signaling pathway.

Huang K, Fang J, Sun W, Zeng Y, Shi B, Ren B Sci Rep. 2024; 14(1):30099.

PMID: 39627300 PMC: 11615303. DOI: 10.1038/s41598-024-81332-y.

Bilobalide Activates Autophagy and Enhances the Efficacy of Bone Marrow Mesenchymal Stem Cells on Spinal Cord Injury Via Upregulating FMRP to Promote WNK1 mRNA Decay.

Chen M, Xu G, Guo W, Lin Y, Yao Z Neurochem Res. 2024; 50(1):33.

PMID: 39601946 DOI: 10.1007/s11064-024-04287-6.

Combination of Adult Mesenchymal Stem Cell Therapy and Immunomodulation with Dimethyl Fumarate Following Spinal Cord Ventral Root Repair.

Gelinski Kempe P, Castro M, Coser L, Cartarozzi L, Barraviera B, Ferreira Jr R Biology (Basel). 2024; 13(11).

PMID: 39596908 PMC: 11591889. DOI: 10.3390/biology13110953.

Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models.

Ye Z, Zheng Y, Li N, Zhang H, Li Q, Wang X Front Mol Neurosci. 2024; 17:1448777.

PMID: 39169950 PMC: 11335736. DOI: 10.3389/fnmol.2024.1448777.

Development of Combinatorial Therapeutics for Spinal Cord Injury using Stem Cell Delivery.

Baek I, Song Y J Vis Exp. 2024; (208).

PMID: 38912769 PMC: 11292835. DOI: 10.3791/66872.

References

Ogle M, Doron G, Levy M, Temenoff J . Hydrogel Culture Surface Stiffness Modulates Mesenchymal Stromal Cell Secretome and Alters Senescence. Tissue Eng Part A. 2020; 26(23-24):1259-1271. DOI: 10.1089/ten.tea.2020.0030. View

Gao X, Han Z, Huang C, Lei H, Li G, Chen L . An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury. Bioact Mater. 2022; 18:569-582. PMC: 9256979. DOI: 10.1016/j.bioactmat.2022.05.026. View

Tator C, Fehlings M . Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991; 75(1):15-26. DOI: 10.3171/jns.1991.75.1.0015. View

Susarla B, Laing E, Yu P, Katagiri Y, Geller H, Symes A . Smad proteins differentially regulate transforming growth factor-β-mediated induction of chondroitin sulfate proteoglycans. J Neurochem. 2011; 119(4):868-78. PMC: 3197872. DOI: 10.1111/j.1471-4159.2011.07470.x. View

Sykova E, Homola A, Mazanec R, Lachmann H, Konradova S, Kobylka P . Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury. Cell Transplant. 2007; 15(8-9):675-87. DOI: 10.3727/000000006783464381. View

Chhabra H, Sarda K . Clinical translation of stem cell based interventions for spinal cord injury - Are we there yet?. Adv Drug Deliv Rev. 2017; 120:41-49. DOI: 10.1016/j.addr.2017.09.021. View

Kigerl K, Gensel J, Ankeny D, Alexander J, Donnelly D, Popovich P . Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci. 2009; 29(43):13435-44. PMC: 2788152. DOI: 10.1523/JNEUROSCI.3257-09.2009. View

Okuda A, Horii-Hayashi N, Sasagawa T, Shimizu T, Shigematsu H, Iwata E . Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. J Neurosurg Spine. 2016; 26(3):388-395. DOI: 10.3171/2016.8.SPINE16250. View

Hu L, Yin C, Zhao F, Ali A, Ma J, Qian A . Mesenchymal Stem Cells: Cell Fate Decision to Osteoblast or Adipocyte and Application in Osteoporosis Treatment. Int J Mol Sci. 2018; 19(2). PMC: 5855582. DOI: 10.3390/ijms19020360. View

10.

Han D, Wu C, Xiong Q, Zhou L, Tian Y . Anti-inflammatory Mechanism of Bone Marrow Mesenchymal Stem Cell Transplantation in Rat Model of Spinal Cord Injury. Cell Biochem Biophys. 2014; 71(3):1341-7. DOI: 10.1007/s12013-014-0354-1. View

11.

Gadani S, Walsh J, Lukens J, Kipnis J . Dealing with Danger in the CNS: The Response of the Immune System to Injury. Neuron. 2015; 87(1):47-62. PMC: 4491143. DOI: 10.1016/j.neuron.2015.05.019. View

12.

Hill R, Zhang Y, Burke D, DeVries W, Zhang Y, Magnuson D . Anatomical and functional outcomes following a precise, graded, dorsal laceration spinal cord injury in C57BL/6 mice. J Neurotrauma. 2009; 26(1):1-15. PMC: 2991182. DOI: 10.1089/neu.2008.0543. View

13.

Menezes K, Nascimento M, Goncalves J, Cruz A, Lopes D, Curzio B . Human mesenchymal cells from adipose tissue deposit laminin and promote regeneration of injured spinal cord in rats. PLoS One. 2014; 9(5):e96020. PMC: 4022508. DOI: 10.1371/journal.pone.0096020. View

14.

Assuncao Silva R, Pinto L, Salgado A . Cell transplantation and secretome based approaches in spinal cord injury regenerative medicine. Med Res Rev. 2021; 42(2):850-896. DOI: 10.1002/med.21865. View

15.

Imai T, Takahashi Y, Nishikawa M, Kato K, Morishita M, Yamashita T . Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J Extracell Vesicles. 2015; 4:26238. PMC: 4323410. DOI: 10.3402/jev.v4.26238. View

16.

Guest J, Datta N, Jimsheleishvili G, Gater Jr D . Pathophysiology, Classification and Comorbidities after Traumatic Spinal Cord Injury. J Pers Med. 2022; 12(7). PMC: 9323191. DOI: 10.3390/jpm12071126. View

17.

Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D . Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell. 2012; 150(6):1264-73. PMC: 3445432. DOI: 10.1016/j.cell.2012.08.020. View

18.

Zeng X, Zeng Y, Ma Y, Lu L, Du B, Zhang W . Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation, promote angiogenesis, and reduce cavity formation in experimental spinal cord injury. Cell Transplant. 2011; 20(11-12):1881-99. DOI: 10.3727/096368911X566181. View

19.

Chhabra H, Sarda K, Arora M, Sharawat R, Singh V, Nanda A . Autologous bone marrow cell transplantation in acute spinal cord injury--an Indian pilot study. Spinal Cord. 2015; 54(1):57-64. DOI: 10.1038/sc.2015.134. View

20.

Zhao T, Yan W, Xu K, Qi Y, Dai X, Shi Z . Combined treatment with platelet-rich plasma and brain-derived neurotrophic factor-overexpressing bone marrow stromal cells supports axonal remyelination in a rat spinal cord hemi-section model. Cytotherapy. 2013; 15(7):792-804. DOI: 10.1016/j.jcyt.2013.04.004. View