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Review
. 2019 May 31;20(11):2698.
doi: 10.3390/ijms20112698.

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

Fabio Cofano  1 , Marina Boido  2 , Matteo Monticelli  3 , Francesco Zenga  4 , Alessandro Ducati  5 , Alessandro Vercelli  6 , Diego Garbossa  7
Affiliations
Review

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

Fabio Cofano et al. Int J Mol Sci. .

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.

Keywords: mesenchymal stem cells; regenerative medicine; spinal cord injury; translational medicine.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The main factors and mechanisms influencing mesenchymal stem cell (MSC) homing process are illustrated. (A) When injected either intravenously or intraspinally, MSCs show remarkable properties of “homing”. (B) At the injury site, some molecules (such as VEGF, HGF, cytokines, etc.) are secreted; when transplanted into the spinal parenchyma, MSCs are attracted by chemotactic stimuli and migrate toward the lesion site. (C) Moreover, when injected intravenously, MSCs can interact with endothelial cells through the VLA-4−VCAM-1 interaction; then, the extravasation is mediated by the interaction between the C–X–C chemokine receptor 4 and stromal cell-derived factor-1α (SDF-1), a chemotactic cytokine induced by proinflammatory stimuli. Created with BioRender software.
Figure 2
Figure 2
The main MSC sources, including bone marrow, umbilical cord, adipose tissue, and amnion. MSCs can exert both autocrine and paracrine effects. Among the molecules secreted, we can include several immunomodulatory and trophic factors, and anti-inflammatory cytokines; when transplanted in an injured spinal cord, the grafted cells can positively influence the host environment. Created with BioRender software.
Figure 3
Figure 3
In preclinical experiments, bone marrow (BM)-MSCs can be isolated from femurs of adult mice and expanded in vitro; when cultured, the cells display the typical fibroblast-like shape. Created with BioRender software. Scale bar = 40 μm.
See this image and copyright information in PMC

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