Regulatory Role of Mesenchymal Stem Cells on Secondary Inflammation in Spinal Cord Injury

Overview

Journal J Inflamm Res

Publisher Dove Medical Press

Date 2022 Feb 4

PMID 35115806

Authors

Qi-Ming Pang

Si-Yu Chen

Sheng-Ping Fu

Hui Zhou

Qian Zhang

Jun Ao

Xiao-Ping Luo

Tao Zhang

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) is a catastrophic condition with high morbidity and mortality that still lacks effective therapeutic strategies. It is well known that the most important stage in SCI pathogenesis is secondary injury, and among the involved mechanisms, the inflammatory cascade is the main contributor and directly influences neurological function recovery. In recent years, increasing evidence has shown that mesenchymal stem cells (MSCs) transplantation is a promising immunomodulatory strategy. Transplanted MSCs can regulate macrophage-, astrocyte-, and T lymphocyte-mediated neuroinflammation and help create a microenvironment that facilitates tissue repair and regeneration. This review focuses on the effects of different types of immune cells and MSCs, specifically the immunoregulatory capacity of MSCs in SCI and repair. We will also discuss how to exploit MSCs transplantation to regulate immune cells and develop novel therapeutic strategies for SCI.

Citing Articles

Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery.

Trinh Q, Mai H, Pham D Regen Ther. 2024; 26:981-989.

PMID: 39524179 PMC: 11550585. DOI: 10.1016/j.reth.2024.09.014.

The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.

Mishra R, Nielsen B, Trudrung M, Lee S, Bolstad L, Hellenbrand D Cells. 2024; 13(18).

PMID: 39329731 PMC: 11430430. DOI: 10.3390/cells13181547.

Adipose-Derived Stem Cell Therapy in Spinal Cord Injury.

El Masri J, Fadlallah H, Al Sabsabi R, Afyouni A, Al-Sayegh M, Abou-Kheir W Cells. 2024; 13(17.

PMID: 39273075 PMC: 11394073. DOI: 10.3390/cells13171505.

The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions.

Kerkis I, da Silva A, Araldi R Front Immunol. 2024; 15:1400533.

PMID: 39015561 PMC: 11249726. DOI: 10.3389/fimmu.2024.1400533.

Recent Advances in the Treatment of Spinal Cord Injury.

Yari D, Saberi A, Salmasi Z, Ghoreishi S, Etemad L, Movaffagh J Arch Bone Jt Surg. 2024; 12(6):380-399.

PMID: 38919744 PMC: 11195032. DOI: 10.22038/ABJS.2023.73944.3424.

References

Luz-Crawford P, Kurte M, Bravo-Alegria J, Contreras R, Nova-Lamperti E, Tejedor G . Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther. 2013; 4(3):65. PMC: 3706898. DOI: 10.1186/scrt216. View

Wang S, Jia Y, Cao X, Feng S, Na L, Dong H . HUCMSCs transplantation combined with ultrashort wave therapy attenuates neuroinflammation in spinal cord injury through NUR77/ NF-κB pathway. Life Sci. 2020; 267:118958. DOI: 10.1016/j.lfs.2020.118958. 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

Lv X, Wang L, Zou X, Huang S . Umbilical Cord Mesenchymal Stem Cell Therapy for Regenerative Treatment of Rheumatoid Arthritis: Opportunities and Challenges. Drug Des Devel Ther. 2021; 15:3927-3936. PMC: 8462093. DOI: 10.2147/DDDT.S323107. View

Li Q, Lian Y, Deng Y, Chen J, Wu T, Lai X . mRNA-engineered mesenchymal stromal cells expressing CXCR2 enhances cell migration and improves recovery in IBD. Mol Ther Nucleic Acids. 2021; 26:222-236. PMC: 8413681. DOI: 10.1016/j.omtn.2021.07.009. View

Liu W, Wang Y, Gong F, Rong Y, Luo Y, Tang P . Exosomes Derived from Bone Mesenchymal Stem Cells Repair Traumatic Spinal Cord Injury by Suppressing the Activation of A1 Neurotoxic Reactive Astrocytes. J Neurotrauma. 2018; 36(3):469-484. DOI: 10.1089/neu.2018.5835. View

Zou H, Guo S, Zhu L, Xu X, Liu J . Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models. Front Neurosci. 2021; 15:628917. PMC: 8200570. DOI: 10.3389/fnins.2021.628917. View

Zhang H, Younsi A, Zheng G, Tail M, Harms A, Roth J . Sonic Hedgehog modulates the inflammatory response and improves functional recovery after spinal cord injury in a thoracic contusion-compression model. Eur Spine J. 2021; 30(6):1509-1520. DOI: 10.1007/s00586-021-06796-2. View

Li Z, Wang Q, Hu H, Zheng W, Gao C . Research advances of biomaterials-based microenvironment-regulation therapies for repair and regeneration of spinal cord injury. Biomed Mater. 2021; 16(5). DOI: 10.1088/1748-605X/ac1d3c. View

10.

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

11.

Lin W, Chen W, Liu W, Xu Z, Zhang L . Sirtuin4 suppresses the anti-neuroinflammatory activity of infiltrating regulatory T cells in the traumatically injured spinal cord. Immunology. 2019; 158(4):362-374. PMC: 6856927. DOI: 10.1111/imm.13123. View

12.

Takafuji Y, Hori M, Mizuno T, Harada-Shiba M . Humoral factors secreted from adipose tissue-derived mesenchymal stem cells ameliorate atherosclerosis in Ldlr-/- mice. Cardiovasc Res. 2018; 115(6):1041-1051. DOI: 10.1093/cvr/cvy271. View

13.

Talaat R, Mohamed S, Bassyouni I, Raouf A . Th1/Th2/Th17/Treg cytokine imbalance in systemic lupus erythematosus (SLE) patients: Correlation with disease activity. Cytokine. 2015; 72(2):146-53. DOI: 10.1016/j.cyto.2014.12.027. View

14.

Matsushita T, Lankford K, Arroyo E, Sasaki M, Neyazi M, Radtke C . Diffuse and persistent blood-spinal cord barrier disruption after contusive spinal cord injury rapidly recovers following intravenous infusion of bone marrow mesenchymal stem cells. Exp Neurol. 2015; 267:152-64. DOI: 10.1016/j.expneurol.2015.03.001. View

15.

Gaire B, Choi J . Critical Roles of Lysophospholipid Receptors in Activation of Neuroglia and Their Neuroinflammatory Responses. Int J Mol Sci. 2021; 22(15). PMC: 8346064. DOI: 10.3390/ijms22157864. View

16.

Rahimi K, Ahmadi A, Hassanzadeh K, Soleimani Z, Sathyapalan T, Mohammadi A . Targeting the balance of T helper cell responses by curcumin in inflammatory and autoimmune states. Autoimmun Rev. 2019; 18(7):738-748. DOI: 10.1016/j.autrev.2019.05.012. View

17.

Akhmetzyanova E, Kletenkov K, Mukhamedshina Y, Rizvanov A . Different Approaches to Modulation of Microglia Phenotypes After Spinal Cord Injury. Front Syst Neurosci. 2019; 13:37. PMC: 6718713. DOI: 10.3389/fnsys.2019.00037. View

18.

Liu R, Wang W, Wang S, Xie W, Li H, Ning B . microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling. Aging (Albany NY). 2018; 10(6):1474-1488. PMC: 6046223. DOI: 10.18632/aging.101484. View

19.

Brambilla R, Hurtado A, Persaud T, Esham K, Pearse D, Oudega M . Transgenic inhibition of astroglial NF-kappa B leads to increased axonal sparing and sprouting following spinal cord injury. J Neurochem. 2009; 110(2):765-78. PMC: 4090052. DOI: 10.1111/j.1471-4159.2009.06190.x. View

20.

Markov A, Thangavelu L, Aravindhan S, Zekiy A, Jarahian M, Chartrand M . Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders. Stem Cell Res Ther. 2021; 12(1):192. PMC: 7971361. DOI: 10.1186/s13287-021-02265-1. View