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Fracaro et al. Neuroimmunol Neuroinflammation 2020;7:1-12 I http://dx.doi.org/10.20517/2347-8659.2019.009 Page 9

CHALLENGES AND PERSPECTIVES
SCI has been extensively studied and its mechanism is already known. Many preclinical and clinical studies
have already been performed using drugs associated with SCI, neurotrophic factors, and stem cells. In
cell therapy, several cell types and sources have already been tested. Embryonic stem cells involve ethical
issues and chromosomal instability that make them difficult to use in clinical trials. MSCs have emerged
as an alternative, but with a more limited differentiation capacity. Studies have already demonstrated the
effectiveness of these MSCs in SCI, but the next challenges are to identify the type of cell that has the most
appropriate potential to support SCI regeneration and develop an infusion methodology that can overcome
the hostile microenvironment and facilitate MSCs delivery in damaged neural tissue. Understanding
how the reorganization of injured neural tissues associated with MSCs is also crucial for restoring neural
function but remains largely unknown and needs further clarification. While addressing these challenges,
it is still necessary to maintain the safety of patients involved in the studies, as the mechanisms of action of
stem cells are not yet fully described.

CONCLUSION
SCI is a serious disease which generates disability with unknown cure. Different treatments have already
been developed but none of them has tissue regeneration as a result. Mesenchymal stromal cells seem to
be a promising alternative because, in addition to tissue regeneration, they can act to improve the inflamed
environment through immunomodulation, release of bioactive factors, and restoration of axon myelin.
Preclinical and clinical research studies will enable the definition of the best source of MSCs, cell number,
route of infusion, and number of infusions that may lead to clinical improvement for SCI patients.

Animal model and human clinical studies have shown the regenerative and neuroprotective potential of
MSCs from different sources. In addition, it is interesting to note the absence of adverse effects after MSCs
infusion. MSCs emerge as a new alternative therapy because they are not limited by the time of injury,
showing promising results in patients with acute and chronic lesions, or by the type of injury, resulting in
improvements in patients with complete and incomplete SCI.

DECLARATIONS

Authors’ Contributions
Designed of the work, summarized the references and wrote the manuscript: Fracaro L
Summarized the references, wrote the manuscript, prepared the figures: Zoehler B
Discussed paper writing and revised the manuscript: Rebelatto CLK

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.