4.6. MicroRNAs

MicroRNAs (miRNAs) have been recognized to play crucial roles in regulating growth signals and immune response [28]. Following SCI, microRNAs play important role in inflammatory pathways or in the invading immune cells. Soon after the SCI, damaged area is infiltrated with blood immune cells [29]. MicroRNAs control upregulation of vascular cell adhesion molecule (VCAM1)-mRNA [25] with downregulation of miR-126 [30]. Neutrophil infiltration clarifies upregulation of miR-223 [31], while overexpression of lymphocyte-specific miR-142 [26] associates with the aggregation of immune cells in the injured site during initial days [32]. Moreover, miRNAs are associated with microglia and macrophages activation. Mainly, the downregulation of miR-124 is associated with microglia by directing CCAAT enhancer-binding protein alpha (CEBPα), which is a principal transcription factor vital for myeloid cells development [33]. After SCI, MiR-124 shows a constant downregulation that causes microglial activation [32]. Other associated roles of miRNAs during different mechanisms of SCIs have been recently reviewed in [34].

5.1. Embryo-derived cell population

replace damaged/loss neurological cells, resulting functional recovery from SCI.

Although ethical issues are associated with the origin of embryonic stem cells (ESC), their potential use might significantly results into numerous scientific and clinical applications, especially if they are differentiated into desired cell types and are utilized to develop functional body organs [36]. The ESCs have been considered as a leading candidate of therapeutic cells for numerous types of disorders triggered by loss of cells/tissue or any abnormal body function [37]. A gap that has been produced in spinal cord after traumatic or non-traumatic injury can be refilled via new cell transplantation. To date, embryonic stem cells are considered as the most appropriate type of cells that can be used for this purpose. These are the immature cells that can differentiate into any of a cell type in human body including the cells of CNS and PNS. ESCs have been reported to form a bridge across the injury site, as well as they are capable of excreting neuroprotective factors that reduce the harmful effects from inflammation [38–40].

Figure 1. Graphical representation of cellular transplantation and functional recovery from SCI. Therapeutic cells are derived from different types of sources. Following cellular transplantations into injury site, the transplantable cells secret indulgent neurotrophic molecules to boost the regenerative capability, support axonal regeneration and myelination and

Cellular Transplantation-Based Therapeutic Strategies for Spinal Cord Injuries: Preclinical and Clinical…

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5.1.1. Human embryonic stem cell-derived oligodendrocyte progenitors (hESCs-ODPs)

Since the major problem associated to SCIs is "demyelination," a potential treatment option to replace the myelin-forming cells will be of significant interest. For this purpose, a transplantation of hESCs-ODPs into SCI rat model has shown to increase remyelination and promoted improvement in recovery of locomotory function [41]. This study paved the ways for the use of hESCs-ODPs for treatment of SCIs and supported the notion that pre-differentiation of hESCs into active oligodendrocytes progenitors will offer therapeutic option at early time points after
