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Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.
Molecular and Cellular Biology ( IF 5.3 ) Pub Date : 2020-04-13 , DOI: 10.1128/mcb.00508-19
Huda H Al-Khalaf 1, 2, 3 , Hazem Ghebeh 4 , Salma M Wakil 5 , Falah Al-Mohanna 6 , Abdelilah Aboussekhra 7
Affiliation  

During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that these senescence-related active fibroblasts can dedifferentiate proliferating primary human luminal cells to multipotent stem cells in an interleukin-8 (IL-8)-dependent manner. This was confirmed using recombinant IL-8, while the truncated protein was not active. This IL-8-related dedifferentiation of luminal cells was mediated through the STAT3-dependent downregulation of p16INK4A and the microRNA miR-141. Importantly, these in vitro-generated mammary stem cells exhibited high molecular and cellular similarities to human mammary stem cells. They have also shown a long-term mammary gland-reconstituting ability and the capacity to produce milk postdelivery. Thereby, these IL-8-generated mammary stem cells could be of great value for autologous cell therapy procedures and also for biomedical research as well as drug development.

中文翻译:

白细胞介素8将原代人类发光细胞去分化为多能干细胞。

在衰老过程中,细胞可塑性和衰老在组织再生和包括癌症在内的各种疾病的发病机理中起着重要作用。我们最近显示衰老的乳腺腔细胞可以激活其相邻的基质成纤维细胞。在本报告中,我们提供了明确的证据,这些衰老相关的活性成纤维细胞可以以白介素8(IL-8)依赖性方式将增殖的原代人腔细胞向多能干细胞分化。使用重组IL-8证实了这一点,而截短的蛋白没有活性。这种IL-8相关的腔细胞去分化是通过p16INK4A和microRNA miR-141的STAT3依赖性下调介导的。重要的,这些体外产生的乳腺干细胞表现出与人类乳腺干细胞的分子和细胞相似性。他们还显示了长期的乳腺重构能力和分娩后生产牛奶的能力。因此,这些IL-8产生的乳腺干细胞对于自体细胞治疗程序以及生物医学研究以及药物开发都具有巨大的价值。
更新日期:2020-02-03
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