Department of Endocrinology, First Medical Center of People's Liberation Army General Hospital, Beijing, China.
Department of Endocrinology, Beijing Rehabilitation Hospital of Capital Medical University, Beijing, China.
Cytotherapy. 2021 Jun;23(6):510-520. doi: 10.1016/j.jcyt.2021.01.005. Epub 2021 Mar 16.
The authors aimed to observe β-cell dedifferentiation in type 2 diabetes mellitus (T2DM) and investigate the reversal effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on early- and late-stage β-cell dedifferentiation.
In high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mice, the authors examined the predominant role of β-cell dedifferentiation over apoptosis in the development of T2DM and observed the reversion of β-cell dedifferentiation by UC-MSCs. Next, the authors used db/db mice to observe the progress of β-cell dedifferentiation from early to late stage, after which UC-MSC infusions of the same amount were performed in the early and late stages of dedifferentiation. Improvement in metabolic indices and restoration of β-cell dedifferentiation markers were examined.
In HFD/STZ-induced T2DM mice, the proportion of β-cell dedifferentiation was much greater than that of apoptosis, demonstrating that β-cell dedifferentiation was the predominant contributor to T2DM. UC-MSC infusions significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In db/db mice, UC-MSC infusions in the early stage significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In the late stage, UC-MSC infusions mildly improved glucose homeostasis and partially reversed β-cell dedifferentiation. Combining with other studies, the authors found that the reversal effect of UC-MSCs on β-cell dedifferentiation relied on the simultaneous relief of glucose and lipid metabolic disorders.
UC-MSC therapy is a promising strategy for reversing β-cell dedifferentiation in T2DM, and the reversal effect is greater in the early stage than in the late stage of β-cell dedifferentiation.
作者旨在观察 2 型糖尿病（T2DM）中β细胞去分化，并研究脐带间充质干细胞（UC-MSCs）对早期和晚期β细胞去分化的逆转作用。
在高脂肪饮食（HFD）/链脲佐菌素（STZ）诱导的 T2DM 小鼠中，作者研究了β细胞去分化而非细胞凋亡在 T2DM 发展中的主要作用，并观察了 UC-MSCs 对β细胞去分化的逆转作用。接下来，作者使用 db/db 小鼠观察β细胞从早期到晚期的去分化进展，然后在去分化的早期和晚期进行相同数量的 UC-MSC 输注。检测代谢指标的改善和β细胞去分化标志物的恢复情况。
在 HFD/STZ 诱导的 T2DM 小鼠中，β细胞去分化的比例明显大于细胞凋亡的比例，表明β细胞去分化是 T2DM 的主要原因。UC-MSC 输注显著改善了葡萄糖稳态并逆转了β细胞去分化。在 db/db 小鼠中，早期 UC-MSC 输注显著改善了葡萄糖稳态并逆转了β细胞去分化。在晚期，UC-MSC 输注轻度改善了葡萄糖稳态并部分逆转了β细胞去分化。结合其他研究，作者发现 UC-MSCs 对β细胞去分化的逆转作用依赖于同时缓解葡萄糖和脂质代谢紊乱。
UC-MSC 治疗是逆转 T2DM 中β细胞去分化的一种有前途的策略，在β细胞去分化的早期阶段逆转效果大于晚期阶段。
