Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, ARB Suite 2116, 1406 South Coulter Street, Amarillo, TX 79106, USA.
Cells. 2022 Aug 4;11(15):2409. doi: 10.3390/cells11152409.
Despite advances in diabetic wound care, many amputations are still needed each year due to their diabetic wounds, so a more effective therapy is warranted. Herein, we show that the dental pulp-derived stem cell (DPSC) products are effective in wound healing in diabetic NOD/SCID mice. Our results showed that the topical application of DPSC secretory products accelerated wound closure by inducing faster re-epithelialization, angiogenesis, and recellularization. In addition, the number of neutrophils producing myeloperoxidase, which mediates persisting inflammation, was also reduced. NFκB and its downstream effector molecules like IL-6 cause sustained pro-inflammatory activity and were reduced after the application of DPSC products in the experimental wounds. Moreover, the DPSC products also inhibited the activation of NFκB, and its translocation to the nucleus, by which it initiates the inflammation. Furthermore, the levels of TGF-β, and IL-10, potent anti-inflammatory molecules, were also increased after the addition of DPSC products. Mechanistically, we showed that this wound-healing process was mediated by the upregulation and activation of Smad 1 and 2 molecules. In sum, we have defined the cellular and molecular mechanisms by which DPSC products accelerated diabetic wound closure, which can be used to treat diabetic wounds in the near future.
尽管糖尿病伤口护理取得了进展，但每年仍有许多患者因糖尿病伤口需要截肢，因此需要更有效的治疗方法。在此，我们展示了牙髓干细胞（DPSC）产品在糖尿病 NOD/SCID 小鼠的伤口愈合中是有效的。我们的结果表明，DPSC 分泌产物的局部应用通过诱导更快的再上皮化、血管生成和再细胞化来加速伤口闭合。此外，产生髓过氧化物酶的中性粒细胞数量也减少了，髓过氧化物酶介导持续的炎症。NFκB 及其下游效应分子如 IL-6 引起持续的促炎活性，在实验性伤口中应用 DPSC 产物后减少。此外，DPSC 产物还通过抑制 NFκB 的激活及其向细胞核的易位来抑制炎症的发生，从而启动炎症。此外，添加 DPSC 产物后，TGF-β和 IL-10 等有效的抗炎分子的水平也增加了。从机制上讲，我们表明，这种伤口愈合过程是通过 Smad 1 和 2 分子的上调和激活来介导的。总之，我们已经确定了 DPSC 产品加速糖尿病伤口闭合的细胞和分子机制，这可用于治疗糖尿病伤口。
