Lv Xue, Niu Wenjing, Zhang Bin, Chen Jingbo, Yang Shicong, Xue Yuhuan, Dong Yutian, Yuan Peiyan, Pan Yue, Tan Jeremy, Yang Yi Yan, Ding Xin, Zhao Xiaomiao
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, 518107, China.
Department of Reproductive Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, 106 Zhongshan 2nd Road, Guangzhou, 510080, China.
Adv Healthc Mater. 2024 Dec;13(32):e2400524. doi: 10.1002/adhm.202400524. Epub 2024 Aug 15.
Endometrial injury is a major cause of infertility and recurrent miscarriage. However, no clinically available methods currently exist to effectively repair the damaged endometrium. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for promoting tissue regeneration, yet a biocompatible scaffold capable of delivering MSCs and supporting their growth is needed. Herein, the study reports a peptide hydrogel scaffold, self-assembled from a peptide IVK8-RGD consisting of an ionic complementary peptide sequence IEVEIRVK and a bioactive sequence RGD, to load umbilical cord-derived mesenchymal stem cells (UC-MSCs). This peptide forms a hydrogel under the physiological condition through self-assembly, and the peptide hydrogel exhibits injectability and adhesiveness to uterus, making it suitable for endometrial repair. Importantly, this hydrogel supports the adhesion and proliferation of UC-MSCs in a 3D environment. In vivo experiments using rats with endometrial injury have shown that treatment with IVK8-RGD hydrogel loaded with UC-MSCs effectively restores endometrial thickness, inhibits fibrosis, and facilitates angiogenesis through activating Raf/MEK/ERK pathway, leading to significantly improved fertility and live birth rate. These findings demonstrate the potential of the UC-MSCs-loaded hydrogel in repairing damaged endometrium and may address the unmet clinical needs of treating recurrent miscarriage and infertility induced by endometrial damage.
子宫内膜损伤是不孕和复发性流产的主要原因。然而，目前尚无临床可用的方法来有效修复受损的子宫内膜。间充质干细胞（MSCs）已成为促进组织再生的一种有前景的治疗方法，但需要一种能够递送MSCs并支持其生长的生物相容性支架。在此，该研究报道了一种肽水凝胶支架，它由包含离子互补肽序列IEVEIRVK和生物活性序列RGD的肽IVK8-RGD自组装而成，用于负载脐带间充质干细胞（UC-MSCs）。这种肽在生理条件下通过自组装形成水凝胶，并且该肽水凝胶具有可注射性和对子宫的粘附性，使其适用于子宫内膜修复。重要的是，这种水凝胶在三维环境中支持UC-MSCs的粘附和增殖。使用子宫内膜损伤大鼠进行的体内实验表明，用负载UC-MSCs的IVK8-RGD水凝胶治疗可有效恢复子宫内膜厚度，抑制纤维化，并通过激活Raf/MEK/ERK途径促进血管生成，从而显著提高生育力和活产率。这些发现证明了负载UC-MSCs的水凝胶在修复受损子宫内膜方面的潜力，并可能满足治疗由子宫内膜损伤引起的复发性流产和不孕的未满足的临床需求。
