Stem Cell Therapies for Cervical Spinal Cord Injury

Abstract

Cervical-level injuries account for the majority of presented spinal cord injuries (SCIs), yet there are few therapies that successfully improve the overall quality of life for patients. Regenerative therapies aimed at ameliorating deficits in respiratory and motor function are urgently needed. Cellular transplantation strategies are a promising therapeutic avenue. These strategies seek to overcome the inhibitory environment of the injury site, increase native regenerative capacities, provide scaffolding to bridge the lesion, or replace injury-lost neurons and glia.Numerous considerations must be taken into account, however, when designing effective cellular transplantation therapies, most notably of which is cell source. Each cell source offers its own unique attributes-both positive and negative-that directly correspond with functional outcomes and clinical translation. Here we discuss three different cell types currently used in cellular transplantation strategies to treat cervical SCIs: mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). By illustrating the characteristics of each cell type and outlining the studies and clinical trials in which they have been featured, we hope to provide the reader with a detailed understanding of both their capabilities and also their potential drawbacks in experimental and clinical settings.

Prerequisites for Mesenchymal Stem Cell Transplantation in Spinal Cord Injury

“…Present around blood vessels, mesenchymal stem cells respond more readily to tissue damage [3]. The transdifferentiation capacity of mesenchymal stem cells into neuronal and glial lineages has been debated; transplanted mesenchymal stem cells do not differentiate into a neuronal fate, even if they display weak expression of NeuN (a neuronal marker) [3].…”

“…Bone marrow stromal cell transplantation has been shown to overcome the gliosis [3]. They have been reported to enhance neuronal protection and cellular preservation via reduction in injury-induced sensitivity to mechanical trauma.…”

“…Human umbilical cord blood-derived mesenchymal stem cells (whether Wharton's jelly mesenchymal stem cells or human umbilical cord perivascular cells) may reverse spinal cord injury pathophysiology by downregulating apoptotic genes and secreting neurotrophic factors in few days; they may transdifferentiate toward neuronal and oligodendroglial phenotypes [3]. Intrathecal transplantation of human amniotic mesenchymal stem cells has promoted functional recovery in a rat model of traumatic spinal cord injury [148] and in a chronic constrictive nerve injury model [149].…”

“…The potency of mesenchymal stem cells exhibits significant age and donor variation [3,[184][185][186].…”

“…Nevertheless, ever since, the number of clinical trials have been increased. Mesenchymal stem cells, in particular, are easy to isolate, can be rapidly expanded in culture and can be cryopreserved without loss of potency [3,4]. Clinical reports on their use have varied, starting from documenting their safety [5,6] up to limited clinical efficacy [7], even partial or complete efficacy [8][9][10][11].…”