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Adv Pharm Bull. 2023;13(4): 806-816.
doi: 10.34172/apb.2023.058
PMID: 38022812
PMCID: PMC10676545
  Abstract View: 658
  PDF Download: 526

Research Article

Human Mesenchymal Stem Cell Transplantation Improved Functional Outcomes Following Spinal Cord Injury Concomitantly with Neuroblast Regeneration

Maryam Lale Ataei 1,2 ORCID logo, Mohammad Karimipour 2* ORCID logo, Parviz Shahabi 3,4* ORCID logo, Hamid Soltani-Zangbar 5 ORCID logo, Maryam Pashaiasl 2,6,7* ORCID logo

1 Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
3 Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
5 Department of Neuroscience and Cognition, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
6 Department of Reproductive Biology, Faculty of Advanced Medical Science, Tabriz University of Medical Science, Tabriz, Iran.
7 Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
*Corresponding Authors: Mohammad Karimipour, Email: karimipourm@tbzmed.ac.ir; Parviz Shahabi, Email: parvizshahabi@gmail.com; Maryam Pashaiasl, Email: Pashaim@tbzmed.ac.ir

Abstract

Purpose: Spinal cord injury (SCI) is damage to the spinal cord that resulted in irreversible neuronal loss, glial scar formation and axonal injury. Herein, we used the human amniotic fluid mesenchymal stem cells (hAF-MSCs) and their conditioned medium (CM), to investigate their ability in neuroblast and astrocyte production as well as functional recovery following SCI.

Methods: Fifty-four adult rats were randomly divided into nine groups (n=6), included: Control, SCI, (SCI+DMEM), (SCI+CM), (SCI+MSCs), (SCI+Astrocyte), (SCI+Astrocyte+DMEM), (SCI+Astrocyte+CM) and (SCI+Astrocyte+MSCs). Following laminectomy and SCI induction, DMEM, CM, MSCs, and astrocytes were injected. Western blot was performed to explore the levels of the Sox2 protein in the MSCs-CM. The immunofluorescence staining against doublecortin (DCX) and glial fibrillary acidic protein (GFAP) was done. Finally, Basso-Beattie-Brenham (BBB) locomotor test was conducted to assess the neurological outcomes.

Results: Our results showed that the MSCs increased the number of endogenous DCX-positive cells and decreased the number of GFAP-positive cells by mediating juxtacrine and paracrine mechanisms (P<0.001). Transplanted human astrocytes were converted to neuroblasts rather than astrocytes under influence of MSCs and CM in the SCI. Moreover, functional recovery indexes were promoted in those groups that received MSCs and CM.

Conclusion: Taken together, our data indicate the MSCs via juxtacrine and paracrine pathways could direct the spinal cord endogenous neural stem cells (NSCs) to the neuroblasts lineage which indicates the capability of the MSCs in the increasing of the number of DCX-positive cells and astrocytes decline.

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Submitted: 15 Jun 2022
Revision: 12 Sep 2022
Accepted: 16 Oct 2022
ePublished: 20 Oct 2022
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