Identification of Novel Multipotent Stem Cells in Mouse Spinal Cord Following Traumatic Injury

SOX2 生物 干细胞 内斯汀 多能干细胞 脊髓损伤 神经干细胞 神经发生 细胞生物学 干细胞标记物 成体干细胞 神经球 脊髓 细胞分化 病理 祖细胞 胚胎干细胞 神经科学 医学 遗传学 基因
作者
Yoji Kuramoto,Toshinori Takagi,Yuki Takeda,Saujanya Rajbhandari,Yasunori Yoshida,Takayuki Nakagomi,Shinichi Yoshimura
出处
期刊:Stem Cells and Development [Mary Ann Liebert, Inc.]
卷期号:31 (17-18): 555-568 被引量:6
标识
DOI:10.1089/scd.2021.0297
摘要

We showed that injury-induced multipotent stem cells (iSCs) emerge in the brain after stroke. These brain-derived iSCs (B-iSCs) can differentiate into various lineages, including neurons. This study aimed to determine whether similar stem cells can be induced even after nonischemic injuries, such as trauma to the spinal cord. We characterized these cells, mainly focusing on their stemness, multipotency, and neuronal differentiation activities. Spinal cord injury (SCI) was produced using forceps in adult mice. On day 3 after SCI, samples were obtained from the injured areas. Spinal cord sections were subjected to histological analyses. Cells were isolated and assessed for proliferative activities, immunohistochemistry, reverse transcriptase-polymerase chain reaction, fluorescence-activated cell sorter, and microarray analysis. Although nerve cell morphology was disrupted within the injured spinal cord, our histological observations revealed the presence of cells expressing stem cells, such as nestin and Sox2 in these areas. In addition, cells extracted from injured areas exhibited high proliferative abilities. These cells also expressed markers of both neural stem cells (eg, nestin, Sox2) and multipotent stem cells (eg, Sox2, c-myc, Klf4). They differentiated into adipocytes, osteocytes, and chondrocytes, as well as neuronal cells. Microarray analysis further identified similar properties between spinal cord (SC)-derived iSCs and B-iSCs. However, SC-iSCs revealed specific genes related to the regulation of stemness and neurogenesis. We identified similar features related to multipotency in SC-iSCs compared with B-iSCs, including neuronal differentiation potential. Although the differences between SC-iSCs and B-iSCs remain largely undetermined, this study shows that iSCs can develop even after nonischemic injuries such as trauma. This phenomenon can occur outside the brain within the central nervous system.
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