The Restorative Effect of Human Amniotic Fluid Stem Cells on Spinal Cord Injury.

Maryam Lale Ataei,Parviz Shahabi,Roghiyeh Pashaei-Asl,Maryam Pashaiasl,Mohammad Karimipour,Esmaeil Ebrahimie

doi:10.3390/cells10102565

Abstract

Spinal cord injury (SCI) is a debilitating condition within the neural system which is clinically manifested by sensory-motor dysfunction, leading, in some cases, to neural paralysis for the rest of the patient’s life. In the current study, mesenchymal stem cells (MSCs) were isolated from the human amniotic fluid, in order to study their juxtacrine and paracrine activities. Flow cytometry analysis was performed to identify the MSCs. A conditioned medium (CM) was collected to measure the level of BDNF, IL-1β, and IL-6 proteins using the ELISA assay. Following the SCI induction, MSCs and CM were injected into the lesion site, and also CM was infused intraperitoneally in the different groups. Two weeks after SCI induction, the spinal cord samples were examined to evaluate the expression of the doublecortin (DCX) and glial fibrillary acid protein (GFAP) markers using immunofluorescence staining. The MSCs’ phenotype was confirmed upon the expression and un-expression of the related CD markers. Our results show that MSCs increased the expression level of the DCX and decreased the level of the GFAP relative to the injury group (p < 0.001). Additionally, the CM promoted the DCX expression rate (p < 0.001) and decreased the GFAP expression rate (p < 0.01) as compared with the injury group. Noteworthily, the restorative potential of the MSCs was higher than that of the CM (p < 0.01). Large-scale meta-analysis of transcriptomic data highlighted PAK5, ST8SIA3, and NRXN1 as positively coexpressed genes with DCX. These genes are involved in neuroactive ligand–receptor interaction. Overall, our data revealed that both therapeutic interventions could promote the regeneration and restoration of the damaged neural tissue by increasing the rate of neuroblasts and decreasing the astrocytes.

Highlights

Spinal cord injury (SCI) is a neurological trauma that leads to neural tissue degeneration and glial scar formation, which may result in permanent disability and insufficient functional recovery for the rest of the patient’s life [1,2]
It should be noted thatthat the the could significantly decrease the expression of relative to the focal administration through IP could significantly decrease the expression of glial fibrillary acid protein (GFAP) relative to the focal administration route. These findings demonstrate that the mesenchymal stem cells (MSCs) and conditioned medium (CM) stimulated the neuroblast proliferation as well as the neurogenesis and decreased the astrocyte proliferation and astrogliosis
We showed that cell therapy using MSCs, immediately after spinal cord injury, has a positive effect on SCI treatment

Summary

Introduction

Spinal cord injury (SCI) is a neurological trauma that leads to neural tissue degeneration and glial scar formation, which may result in permanent disability and insufficient functional recovery for the rest of the patient’s life [1,2]. One of the most considerable outcomes of SCI is the neural cell loss and glial scar formation, which should be taken into therapeutic consideration [4]. The spinal cord lacks neurogenesis ability during adulthood; finding effective therapeutic strategies for repairing and improving the affected spinal cord is very important [7,8]. In this regard, stem cells and their products have been developed as a possible and efficient strategy to help repair the SCI [9,10]. Human amniotic MSCs (hAFMSCs) can endure continuous passages without alteration in the normal phenotype and karyotype during the cell culture [12,13]. hAF-MSCs secrete multiple growth factors (GFs), namely chemokines, exosomes, microvesicles, hormones, and interleukin (IL) in CM [14,15]

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