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

移植 IGF-1 诱导的 BMSC 衍生 NPC 可促进大鼠脊髓损伤模型中的组织修复和运动恢复

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

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.

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