Xia Kaishun, Gong Zhe, Zhu Jian, Yu Wei, Wang Yitian, Wang Junjie, Xu Ankai, Zhou Xiaopeng, Tao Huimin, Li Fangcai, Liang Chengzhen
Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, No. 88 Jie Fang Road, Hangzhou, 310009, Zhejiang, China.
Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
Curr Stem Cell Res Ther. 2019;14(1):57-64. doi: 10.2174/1574888X13666180918095121.
Low back pain (LBP) is one of the world's most common musculoskeletal diseases and is frequently associated with intervertebral disc degeneration (IDD). While the main cause of IDD is commonly attributed to a reduced number of nucleus pulposus (NP) cells, current treatment strategies (both surgical and more conservative) fail to replenish NP cells or reverse the pathology. Cell replacement therapies are an attractive alternative for treating IDD. However, injecting intervertebral disc (IVD) cells, chondrocytes, or mesenchymal stem cells into various animal models of IDD indicate that transplanted cells generally fail to survive and engraft into the avascular IVD niche. Whereas pluripotent stem cells (PSCs), including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), hold great potential for revolutionizing regenerative medicine, current protocols for differentiating these cells into NP-like cells are inadequate. Nucleus pulposus progenitor cells (NPPCs), which are derived from the embryonic notochord, can not only survive within the harsh hypoxic environment of the IVD, but they also efficiently differentiate into NP-like cells. Here we provide an overview of the latest progress in repairing degenerated IVDs using PSCs and NPPCs. We also discuss the molecular pathways by which PSCs differentiate into NPPCs in vitro and in vivo and propose a new, in vivo IDD therapy.
下腰痛（LBP）是世界上最常见的肌肉骨骼疾病之一，常与椎间盘退变（IDD）相关。虽然IDD的主要原因通常归因于髓核（NP）细胞数量减少，但目前的治疗策略（包括手术和更保守的治疗）都无法补充NP细胞或逆转病理状态。细胞替代疗法是治疗IDD的一种有吸引力的替代方法。然而，将椎间盘（IVD）细胞、软骨细胞或间充质干细胞注射到各种IDD动物模型中表明，移植的细胞通常无法存活并植入无血管的IVD微环境中。而多能干细胞（PSC），包括诱导多能干细胞（iPSC）和胚胎干细胞（ESC），在革新再生医学方面具有巨大潜力，但目前将这些细胞分化为NP样细胞的方案并不完善。源自胚胎脊索的髓核祖细胞（NPPC）不仅能在IVD恶劣的低氧环境中存活，还能高效分化为NP样细胞。在此，我们概述了使用PSC和NPPC修复退变IVD的最新进展。我们还讨论了PSC在体外和体内分化为NPPC的分子途径，并提出了一种新的体内IDD治疗方法。
