Al-Zikri Putri Nur Hidayah, Huat Tee Jong, Khan Amir Ali, Patar Azim, Reza Mohammed Faruque, Idris Fauziah Mohamad, Abdullah Jafri Malin, Jaafar Hasnan
Department of Pathology, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.
Department of Neurosciences, School of Medical Sciences, University Sains Malaysia, Kelantan, Malaysia.
Heliyon. 2022 Aug 24;8(8):e10384. doi: 10.1016/j.heliyon.2022.e10384. eCollection 2022 Aug.
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 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.
骨髓间充质干细胞（BMSCs）对脊髓损伤（SCI）具有治疗潜力。我们已经表明，胰岛素样生长因子1（IGF-1）通过下调miR-22-3p来增强BMSCs来源的神经祖细胞（NPCs）的细胞增殖和生存能力。然而，BMSCs来源的NPCs的功能应用尚未得到充分研究。在本研究中，我们证明在BMSCs来源的NPCs中敲低内源性miR-22-3p可上调 表达，导致细胞增殖增强。RNA测序分析揭示了NPCs中3513个差异表达基因。NPCs中上调的基因丰富了与神经系统发育相关的基因本体术语。终末分化的NPCs产生具有神经元样形态和表型的细胞。在SCI大鼠模型中移植NPCs可在移植后4周使运动和感觉功能得到更好的恢复。总之，本研究结果表明，补充IGF-1衍生的NPCs可分化为功能性神经谱系细胞，是SCI干细胞治疗的最佳选择。
