Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy.

Neurogenic tissue nanotransfection in the management of cutaneous diabetic polyneuropathy.
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DOI:
10.1016/j.nano.2020.102220
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发表时间:
2020-08
期刊:
Nanomedicine : nanotechnology, biology, and medicine
影响因子:
--
通讯作者:
Khanna S
Khanna S
中科院分区:
其他
文献类型:
--
作者:
Roy S;Sen CK;Ghatak S;Higuita-Castro N;Palakurti R;Nalluri N;Clark A;Stewart R;Gallego-Perez D;Prater DN;Khanna S

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这项工作依赖于我们最近的报告,成功地使用组织纳米转染(TNT)交付Ascl 1,Brn 2和Myt 11(TNTABM)直接将皮肤成纤维细胞转化为电生理活性诱导的神经元细胞(iN)在体内。在这里,我们报告说,除了成功的神经原性转换的细胞,TNTABM引起神经营养富集的皮肤基质。因此,我们询问是否可以利用皮肤的这种神经营养环境来拯救慢性糖尿病条件下预先存在的神经纤维。局部皮肤TNTABM引起内源性NGF和其他共调节神经营养因子如Nt 3的升高。TNTABM避免了db/db糖尿病小鼠皮肤PGP9.5+成熟神经纤维的损失。这是第一项研究表明,在体内重编程的条件下,组织微环境的变化可以用于治疗目的,例如在糖尿病条件下将预先存在的神经纤维从其可预测的损失路径中拯救出来。
This work rests on our recent report on the successful use of tissue nanotransfection (TNT) delivery of Ascl1, Brn2, and Myt1l (TNTABM) to directly convert skin fibroblasts into electrophysiologically active induced neuronal cells (iN) in vivo. Here we report that in addition to successful neurogenic conversion of cells, TNTABM caused neurotrophic enrichment of the skin stroma. Thus, we asked whether such neurotrophic milieu of the skin can be leveraged to rescue pre-existing nerve fibers under chronic diabetic conditions. Topical cutaneous TNTABM caused elevation of endogenous NGF and other co-regulated neurotrophic factors such as Nt3. TNTABM spared loss of cutaneous PGP9.5+ mature nerve fibers in db/db diabetic mice. This is the first study demonstrating that under conditions of in vivo reprogramming, changes in the tissue microenvironment can be leveraged for therapeutic purposes such as the rescue of pre-existing nerve fibers from its predictable path of loss under conditions of diabetes.
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