1 KU-KIST Graduate School of Converging Science and Technology, Korea University , Seoul, Republic of Korea.
2 Biomaterials Research Center, Korea Institute of Science and Technology , Seoul, Republic of Korea.
Tissue Eng Part A. 2018 Jan;24(1-2):21-33. doi: 10.1089/ten.TEA.2016.0517. Epub 2017 Sep 26.
The wound healing process requires enough blood to supply nutrients and various growth factors to the wound area. However, chronic wounds such as diabetic skin ulcers have limited regeneration due to a lack of cellular and molecular signals because of a deficient blood flow. Mesenchymal stem cells (MSCs) are known to provide various factors, including growth factors, cytokines, and angiogenic mediators. Although MSCs have great therapeutic potential, their transplantation has many obstacles, including the time required to culture the cells, the invasiveness of the procedure, and limited stem cell sources. In this study, we induced a diabetic 1 model in rats aged 7 weeks by injecting streptozotocin and citrate buffer solution. After confirming that diabetes was induced in the rats, we created critical sized wounds on the dorsal area of the rats and then injected hydrogels. We performed the experiments with four groups (defect model for the control, self-assembled peptides (SAPs), SAP with soluble substance P, and SAP conjugated with substance P) to treat the wound defect. Tissues were harvested at 1, 2, and 3 weeks after injection and examined for the wound closure, histological analysis, quantitative real-time polymerase chain reaction analysis, and quantification of collagen deposits to investigate stem cell recruitment and full recovery of wounds at an accelerated time period. As our results show, the wounds treated with SAP and substance P exhibited significantly accelerated wound closure, enhanced collagen deposition, and increased angiogenesis. Furthermore, we confirmed the ability of SAP with substance P to promote the recruitment and homing of cells by immunofluorescence staining of a MSC marker. In addition, it was observed that substance P remained in the wound area up to 3 weeks after the injection of SAP with substance P. It is believed that the endogenous MSCs mobilized by substance P had therapeutic effects through their proper differentiation and release of paracrine factors into the wound sites. In conclusion, this study shows that SAP with substance P can promote wound healing to enhance skin regeneration without cell transplantation in a diabetic model.
伤口愈合过程需要足够的血液为伤口区域提供营养物质和各种生长因子。然而，由于血流不足，糖尿病皮肤溃疡等慢性伤口的细胞和分子信号有限，再生能力有限。间充质干细胞 (MSC) 被认为可以提供各种因子，包括生长因子、细胞因子和血管生成介质。尽管 MSC 具有巨大的治疗潜力，但它们的移植存在许多障碍，包括培养细胞所需的时间、程序的侵入性和有限的干细胞来源。在这项研究中，我们通过注射链脲佐菌素和柠檬酸盐缓冲液在 7 周龄大鼠中诱导糖尿病 1 型模型。在确认大鼠诱导糖尿病后，我们在大鼠背部区域创建了临界尺寸的伤口，然后注射水凝胶。我们用四个组（缺陷模型对照组、自组装肽 (SAP)、含可溶性 P 物质的 SAP 和与 P 物质偶联的 SAP）进行实验来治疗伤口缺陷。在注射后 1、2 和 3 周采集组织，检查伤口闭合、组织学分析、定量实时聚合酶链反应分析和胶原蛋白沉积的定量，以研究干细胞募集和加速伤口完全恢复。正如我们的结果所示，SAP 和 P 物质处理的伤口表现出明显加速的伤口闭合、增强的胶原蛋白沉积和增加的血管生成。此外，我们通过 MSC 标志物的免疫荧光染色证实了 SAP 与 P 物质促进细胞募集和归巢的能力。此外，观察到 SAP 与 P 物质注射后 3 周内 P 物质仍留在伤口区域。据信，P 物质动员的内源性 MSC 通过适当的分化并将旁分泌因子释放到伤口部位发挥治疗作用。总之，这项研究表明，SAP 与 P 物质可以促进伤口愈合，增强皮肤再生，而无需在糖尿病模型中进行细胞移植。
