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the use of mesenchymal stem cells in the treatment of spinal cord injury
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the use of mesenchymal stem cells in the treatment of spinal cord injury
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Student ID 170438647Word count: 2091
From mesenchymal stem cells transplantation to cell-free therapies in the treatment of
spinal cord injury.
Abstract
Spinal cord injury (SCI) represents a social and economic burden on society. The critical part
in the pathophysiology of SCI is the uncontrolled, detrimental cascade occurring during the
secondary injury which encompasses vascular changes, inflammation, demyelination and
ultimately cell death and glial scar formation. Considering that the main outcome following
SCI is neuronal loss, the application of stem cells (SCs) represents a promising therapeutic
avenue. In particular, mesenchymal stem cells (MSCs) which for long have dominated the
clinical landscape due to their ubiquity, ease of isolation and more importantly, their
secretome. Despite the encouraging results in preclinical findings, the evidence in clinical
trials is often conflicting. Hence, this review will cover the properties of MSCs, together with
their drawbacks and successful application in SCI.
Introduction
MSCs are adult SCs with the ability to self-renew and give rise to specialised cell types
which contribute to wound healing and tissue regeneration.
They were first discovered in 1968 when Friedenstein observed that transplantation of bone
marrow (BM) into the kidney capsule, resulted in both proliferation of BM cells and the
formation of osseous tissue1. Subsequently, Pittenger and colleagues provided the first in-
depth characterisation of the tri-lineage potential of MSCs, which indicated that these
multipotent SCs can be induced to generate solely osteocytes, adipocytes and chondrocytes2.
Throughout time, various nomenclatures have been used when referring to MSCs, hence, the
“International Society for Cellular Therapy” confirmed the basic criteria necessary to
delineate human MSCs which comprise: (a) being plastic-adherent cells when preserved in
standard culture conditions; (b) simultaneously display the surface markers CD90, CD73 and
CD105 while missing expression of CD19, CD45, CD79a (or CD11b), CD34 and CD14 and
HLA-DR; (c) capability to give rise to chondroblasts, osteoblasts and adipocytes in vitro3.
Regarding the last criterion, it has been claimed that other cells, comprising cardiomyocytes,
, hepatocytes, stromal cells of the BM, smooth muscle cells and neural cells can originate from
MSCs or mesenchymal-like SCs4.
MSCs niche and anatomical location
BM-derived MSCs are the most widely used type of cells in clinical settings, however, since
the procedure is painful and invasive, alternative, discarded tissues are being used as a source
of MSCs, such as umbilical cord, placenta or adipose tissue from liposuction surgeries5.
Furthermore, MSCs can be also found and isolated from other tissues and secretions
including peripheral blood, dental pulp, amniotic fluid, milk from mothers, endometrial and
menstrual blood and others6,7,8,9,10.
Each location in the body that is characterised by the presence of SCs and whose
microenvironment allows them to be preserved in an undifferentiated state is termed niche.
The microenvironment of the niche regulates MSCs potency, proliferation, survival and
differentiation through different cues comprising autocrine, paracrine, neural, physical and
metabolic connections11. It follows that the diverse combination of signals during healing,
development or physiological/pathological states will dictate whether MSCs remain in a
quiescent state or will get activated to contribute to the growth or regeneration demand.
Bearing in mind that MSCs can be isolated from tissue of mesodermal and non-mesodermal
origin, scientists have attempted to uncover if there is a niche common to all the MSCs12.
Indeed, several studies suggest that the MSCs niche may be perivascular in nature (Fig.
1)11,13,14. This would explain the fact that they can be derived by different vascularised sites,
they have a similar gene-expression profile with pericytes, and lastly, by being critical in the
process of healing, MSCs can readily access all tissues from a perivascular niche15.
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