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来自人类皮肤细胞的工程外细胞囊诱导胰腺管道细胞中的亲β细胞转化

Lilibeth Ortega-Pineda¹, Elizabeth Guilfoyle¹, Maria Angelica Rincon-Benavides¹

¹Department of Biomedical Engineering, The Ohio State University, Columbus, OH.

Advanced nanobiomed research

|June 24, 2024

概括

来自人类皮肤纤维细胞的细胞外囊 (EV) 能够有效地将重编程因子传递给胰腺细胞. 这种非病毒方法将细胞转化为潜在的糖尿病细胞疗法.

科学领域:

细胞生物学细胞生物学
再生医学是一种再生医学.
糖尿病研究糖尿病研究

背景情况:

直接核重编程为糖尿病治疗提供了一个有前途的途径,通过产生无干细胞的胰岛素生成β细胞来治疗糖尿病.
目前的重编程策略主要利用病毒载体,这引发了潜在的安全问题.
需要一种非病毒传递系统来推进β细胞替代疗法.

研究的目的:

研究来自人类皮肤纤维细胞 (HDF) 的细胞外囊泡 (EV) 作为重新编程因子的非病毒载体.
评估HDF衍生的EVs在将胰腺管道上皮细胞 (PDCs) 转化为激素表达细胞中的有效性.

主要方法:

人体皮肤纤维细胞 (HDF) 通过编码Pdx1,Ngn3和MafA (PNM) 转录因子的质粒被电传染.
载有PNM的EV被分离并用于治疗胰腺管道上皮细胞 (PDC) 培养物.
在体内验证使用小鼠模型进行了PNM装载EVs的内导注射.

主要成果:

在基因,mRNA和蛋白质水平上,电传输成功地装载了PNM的EV.
装有PNM的EV有效地转化了PDC,增加PNM表达并诱导内分泌细胞标记物 (胰岛素,c-,葡萄糖,Glut2).
在体内研究证实了在小鼠模型中PNM装载的EVs的重编程效果.

结论:

人体皮肤纤维细胞衍生的EV可以作为重新编程因子的有效的非病毒载体.
这种方法促进了PDCs转化为功能性内分泌细胞的转化.
皮肤纤维细胞衍生的EVs代表了针对胰岛素依赖糖尿病的非病毒细胞疗法的潜在平台技术.

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