Niceforo Alessia, Jin Ying, Ramakrishnan Skandha, Lindner-Jackson Maurice, Qiang Liang O, Fischer Itzhak
Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, 19129, USA.
Marion Murray Spinal Cord Research Center, College of Medicine, Drexel University, Philadelphia, PA, 19129, USA.
bioRxiv. 2025 Jun 28:2025.06.27.661961. doi: 10.1101/2025.06.27.661961.
Functional improvement following traumatic spinal cord injury (SCI) remains limited, therefore, it is necessary to develop therapeutic interventions such as cell transplantation to replace lost cells and promote connectivity. While transplantation typically focuses on neurons, it is important to include other neural cells, such as immature astrocytes, to provide a permissive environment, promote neuroprotection and regeneration, and ultimately restore connectivity. In this study, we leveraged cellular engineering using human induced pluripotent stem cells (hiPSCs) to generate astrocyte progenitor cells (hAPCs). We tested two hiPSC lines (WTC11 and KOLF2.1J) to characterize the fate of the hAPCs and following transplantation at the cervical level of the intact spinal cord for up to 3 weeks. Our results demonstrated efficient and consistent differentiation of the hiPSCs into hAPCs, their survival and integration with the adult spinal cord, with no signs of tumors, deleterious outcomes, and unexpected locations. The ability to survive and the absence of adverse effects indicate that hAPC transplantation could be a safe element of therapy in treating spinal cord injuries.
创伤性脊髓损伤(SCI)后的功能改善仍然有限,因此,有必要开发诸如细胞移植等治疗干预措施,以替代受损细胞并促进神经连接。虽然移植通常侧重于神经元,但纳入其他神经细胞(如未成熟星形胶质细胞)很重要,以提供一个有利的环境,促进神经保护和再生,并最终恢复神经连接。在本研究中,我们利用细胞工程技术,使用人类诱导多能干细胞(hiPSC)生成星形胶质细胞祖细胞(hAPC)。我们测试了两条hiPSC系(WTC11和KOLF2.1J),以表征hAPC的命运,并将其移植到完整脊髓的颈部水平长达3周。我们的结果表明,hiPSC能高效且一致地分化为hAPC,它们能够存活并与成年脊髓整合,没有肿瘤迹象、有害结果和异常定位。hAPC存活的能力以及无不良反应表明,hAPC移植可能是治疗脊髓损伤的一种安全的治疗手段。