Division of Urology, Department of Surgery, Harbor-UCLA Medical Center and The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1768, USA.
Int J Mol Sci. 2020 Jul 17;21(14):5045. doi: 10.3390/ijms21145045.
Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.
人类干细胞疗法用于 2 型糖尿病/肥胖症（T2D/O）并发症是通过干细胞自体移植实现的，这些干细胞暴露于有害的 T2D/O 环境中，其效果往往并不理想。我们在 T2D/O 的肥胖 Zucker（OZ）大鼠模型中表明，当这些肌肉源性干细胞（MDSC）来自长期患有 T2D/O 的雄性大鼠时，它们修复勃起功能障碍的效果受损，并且具有异常的基因和 miR-全局转录特征（GTS）印记。通过将正常 MDSC 短期暴露于血脂异常血清中，在体外重现了这种损伤，导致 miR-GTS 改变、脂肪浸润、细胞凋亡、划痕愈合受损和肌肉生长抑制素过表达。在体外，它们的正常对应物（来自 T2D/O 雌性压力性尿失禁大鼠模型的 ZF4-SC）和来自非 T2D/O 瘦女性大鼠的 ZL4-SC 也发生了类似的体外改变。在当前的工作中，我们研究了胆固醇和棕榈酸钠作为脂质因素对 ZF4-SC 和 ZL4-SC 的体外影响。发现了一种类似于由女性血脂异常血清引起的损伤，但两种脂质因素之间存在差异，因此每种因素似乎都专门参与了血脂异常血清在体外和 T2D/O 体内对 MDSC 损伤的作用，而与性别无关。这些结果还证实了 miR-GTS 对 MDSC 损伤的生物标志物价值。
