Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB T2N 1N4, Canada.
Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Health and Environment, 85764 Neuherberg, Germany.
Cells. 2020 Jan 11;9(1):191. doi: 10.3390/cells9010191.
Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another different differentiated cell state avoids the disadvantages of fully reprogramming cells to induced pluripotent stem cells (iPSCs) in terms of faster reprogramming of the needed cells. Trans-differentiation also reduces the risk of tumor formation by avoiding the iPSC state. factors () accompanied by the JAK-STAT pathway inhibition, followed by the introduction of specific differentiation factors, directly reprogrammed mouse embryonic fibroblasts to chondroblasts. Our results showed the absence of intermediate induced pluripotent stem cell formation. The resulting aggregates showed clear hyaline and hypertrophic cartilage. Tumor formation was absent in sub-cutaneous capsules transplanted in SCID mice.
骨关节炎(OA)是透明关节软骨的退行性疾病。这种疾病是进行性的,可能导致残疾。研究人员提出了许多再生方法来治疗骨关节炎,包括干细胞。完全分化的细胞状态直接向另一种不同的分化细胞状态的转分化避免了将细胞完全重编程为诱导多能干细胞(iPSCs)的缺点,因为在需要的细胞中更快地重编程。转分化还通过避免 iPSC 状态降低了肿瘤形成的风险。()因子伴随着 JAK-STAT 通路的抑制,随后引入特定的分化因子,直接将小鼠胚胎成纤维细胞重编程为软骨细胞。我们的结果表明,中间诱导多能干细胞形成的缺失。由此产生的聚集物表现出明显的透明和肥大软骨。在 SCID 小鼠的皮下囊移植中未发现肿瘤形成。