Transplantation of IGF-1-induced BMSC-derived NPCs promotes tissue repair and motor recovery in a rat spinal cord injury model

Putri Nur Hidayah Al-Zikri; Tee Jong Huat; Amir Ali Khan; Azim Patar; Mohammed Faruque Reza; Fauziah Mohamad Idris; Jafri Malin Abdullah; Hasnan Jaafar

doi:10.1016/j.heliyon.2022.e10384

Transplantation of IGF-1-induced BMSC-derived NPCs promotes tissue repair and motor recovery in a rat spinal cord injury model

Heliyon. 2022 Aug 24;8(8):e10384. doi: 10.1016/j.heliyon.2022.e10384. eCollection 2022 Aug.

Authors

Putri Nur Hidayah Al-Zikri^{1

2}, Tee Jong Huat^{3

2}, Amir Ali Khan⁴, Azim Patar^{2

5}, Mohammed Faruque Reza^{2

5}, Fauziah Mohamad Idris⁶, Jafri Malin Abdullah^{2

5}, Hasnan Jaafar¹

Affiliations

¹ Department of Pathology, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.
² Department of Neurosciences, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.
³ Department of Biological Sciences, National University of Singapore 117543, Singapore.
⁴ Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, P. O. Box 27272, United Arab Emirates.
⁵ Brain Behaviour Cluster, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.
⁶ Department of Medical Microbiology, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have therapeutic potential for spinal cord injury (SCI). We have shown that insulin-like growth factor 1 (IGF-1) enhances the cellular proliferation and survivability of BMSCs-derived neural progenitor cells (NPCs) by downregulating miR-22-3p. However, the functional application of BMSCs-derived NPCs has not been investigated fully. In this study, we demonstrate that knockdown of endogenous miR-22-3p in BMSCs-derived NPCs upregulates Akt1 expression, leading to enhanced cellular proliferation. RNASeq analysis reveals 3,513 differentially expressed genes in NPCs. The upregulated genes in NPCs enrich the gene ontology term associated with nervous system development. Terminally differentiated NPCs generate cells with neuronal-like morphology and phenotypes. Transplantation of NPCs in the SCI rat model results in better recovery in locomotor and sensory functions 4 weeks after transplantation. Altogether, the result of this study demonstrate that NPCs derived with IGF-1 supplementation could be differentiated into functional neural lineage cells and are optimal for stem cell therapy in SCI.

Keywords: Cell therapy; Growth factor; Mesenchymal stem cell; Neural differentiation; Spinal cord injury; microRNA.