Mesenchymal Stem Cells for Spinal Cord Injury: Current Options, Limitations, and Future of Cell Therapy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Jun 5

PMID 31159345

Citations 164

Authors

Fabio Cofano

Marina Boido

Matteo Monticelli

Francesco Zenga

Alessandro Ducati

Alessandro Vercelli

Diego Garbossa

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) constitutes an inestimable public health issue. The most crucial phase in the pathophysiological process of SCI concerns the well-known secondary injury, which is the uncontrolled and destructive cascade occurring later with aberrant molecular signaling, inflammation, vascular changes, and secondary cellular dysfunctions. The use of mesenchymal stem cells (MSCs) represents one of the most important and promising tested strategies. Their appeal, among the other sources and types of stem cells, increased because of their ease of isolation/preservation and their properties. Nevertheless, encouraging promise from preclinical studies was followed by weak and conflicting results in clinical trials. In this review, the therapeutic role of MSCs is discussed, together with their properties, application, limitations, and future perspectives.

Citing Articles

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Synergistic restoration of spinal cord injury through hyaluronic acid conjugated hydrogel-polydopamine nanoparticles combined with human mesenchymal stem cell transplantation.

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References

McDonald J, Liu X, Qu Y, Liu S, Mickey S, Turetsky D . Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 1999; 5(12):1410-2. DOI: 10.1038/70986. View

Grandpre T, Nakamura F, Vartanian T, Strittmatter S . Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature. 2000; 403(6768):439-44. DOI: 10.1038/35000226. View

Beattie M, Li Q, Bresnahan J . Cell death and plasticity after experimental spinal cord injury. Prog Brain Res. 2000; 128:9-21. DOI: 10.1016/S0079-6123(00)28003-5. View

Cao Q, Zhang Y, Howard R, Walters W, Tsoulfas P, Whittemore S . Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Exp Neurol. 2001; 167(1):48-58. DOI: 10.1006/exnr.2000.7536. View

Fournier A, Grandpre T, Strittmatter S . Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration. Nature. 2001; 409(6818):341-6. DOI: 10.1038/35053072. View

GROSSMAN S, Rosenberg L, Wrathall J . Relationship of altered glutamate receptor subunit mRNA expression to acute cell loss after spinal cord contusion. Exp Neurol. 2001; 168(2):283-9. DOI: 10.1006/exnr.2001.7629. View

Zuk P, Zhu M, Mizuno H, Huang J, Futrell J, Katz A . Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001; 7(2):211-28. DOI: 10.1089/107632701300062859. View

Hofstetter C, Schwarz E, Hess D, Widenfalk J, El Manira A, Prockop D . Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A. 2002; 99(4):2199-204. PMC: 122342. DOI: 10.1073/pnas.042678299. View

Wurmser A, Gage F . Stem cells: cell fusion causes confusion. Nature. 2002; 416(6880):485-7. DOI: 10.1038/416485a. View

10.

Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni P, Matteucci P . Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002; 99(10):3838-43. DOI: 10.1182/blood.v99.10.3838. View

11.

Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L . G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol. 2002; 3(7):687-94. DOI: 10.1038/ni813. View

12.

Martin D, Cox N, Hathcock T, Niemeyer G, Baker H . Isolation and characterization of multipotential mesenchymal stem cells from feline bone marrow. Exp Hematol. 2002; 30(8):879-86. DOI: 10.1016/s0301-472x(02)00864-0. View

13.

Sankar V, Muthusamy R . Role of human amniotic epithelial cell transplantation in spinal cord injury repair research. Neuroscience. 2003; 118(1):11-7. DOI: 10.1016/s0306-4522(02)00929-6. View

14.

De Ugarte D, Morizono K, Elbarbary A, Alfonso Z, ZuK P, Zhu M . Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs. 2003; 174(3):101-9. DOI: 10.1159/000071150. View

15.

REXED B . A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol. 1954; 100(2):297-379. DOI: 10.1002/cne.901000205. View

16.

Blight A . Spinal cord injury models: neurophysiology. J Neurotrauma. 1992; 9(2):147-9; discussion 149-50. DOI: 10.1089/neu.1992.9.147. View

17.

Kozorovitskiy Y, Gould E . Stem cell fusion in the brain. Nat Cell Biol. 2003; 5(11):952-4. DOI: 10.1038/ncb1103-952. View

18.

Kotobuki N, Hirose M, Takakura Y, Ohgushi H . Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow. Artif Organs. 2004; 28(1):33-9. DOI: 10.1111/j.1525-1594.2004.07320.x. View

19.

REXED B . The cytoarchitectonic organization of the spinal cord in the cat. J Comp Neurol. 1952; 96(3):414-95. DOI: 10.1002/cne.900960303. View

20.

Pera M, Andrade J, Houssami S, Reubinoff B, Trounson A, Stanley E . Regulation of human embryonic stem cell differentiation by BMP-2 and its antagonist noggin. J Cell Sci. 2004; 117(Pt 7):1269-80. DOI: 10.1242/jcs.00970. View