Department of Endocrinology, The Third Affiliated Hospital of Wenzhou Medical University, 325200, Wenzhou, Zhejiang, China.
Department of Interventional Vascular Surgery, The Third Affiliated Hospital of Wenzhou Medical University, No.108 Wansong Road, 325200, Wenzhou, Zhejiang, China.
J Nanobiotechnology. 2023 Jun 27;21(1):202. doi: 10.1186/s12951-023-01925-z.
The employment of stem cells and hydrogel is widespread in contemporary clinical approaches to treating diabetic foot ulcers. However, the hypoxic conditions in the surrounding lesion tissue lead to a low stem cell survival rate following transplantation. This research introduces a novel hydrogel with superior oxygen permeability and biocompatibility, serving as a vehicle for developing a stem cell transplantation system incorporating oxygen-releasing microspheres and cardiosphere-derived stem cells (CDCs). By optimizing the peroxidase fixation quantity on the microsphere surface and the oxygen-releasing microsphere content within the transplantation system, intracellular oxygen levels were assessed using electron paramagnetic resonance (EPR) under simulated low-oxygen conditions in vitro. The expression of vascularization and repair-related indexes were evaluated via RT-PCR and ELISA. The microspheres were found to continuously release oxygen for three weeks within the transplantation system, promoting growth factor expression to maintain intracellular oxygen levels and support the survival and proliferation of CDCs. Moreover, the effect of this stem cell transplantation system on wound healing in a diabetic foot mice model was examined through an in vivo animal experiment. The oxygen-releasing microspheres within the transplantation system preserved the intracellular oxygen levels of CDCs in the hypoxic environment of injured tissues. By inhibiting the expression of inflammatory factors and stimulating the upregulation of pertinent growth factors, it improved the vascularization of ulcer tissue on the mice's back and expedited the healing of the wound site. Overall, the stem cell transplantation system in this study, based on hydrogels containing CDCs and oxygen-releasing microspheres, offers a promising strategy for the clinical implementation of localized stem cell delivery to improve diabetic foot wound healing.
干细胞和水凝胶的应用在治疗糖尿病足溃疡的当代临床方法中非常广泛。然而，周围病变组织中的缺氧条件导致移植后干细胞的存活率较低。本研究介绍了一种具有卓越氧气渗透性和生物相容性的新型水凝胶，作为一种载体，开发了一种包含释氧微球和心脏球源性干细胞（CDCs）的干细胞移植系统。通过优化微球表面过氧化物酶固定量和移植系统内释氧微球含量，使用电子顺磁共振（EPR）在体外模拟低氧条件下评估细胞内氧水平。通过 RT-PCR 和 ELISA 评估血管生成和修复相关指标的表达。研究发现，微球在移植系统内持续释放氧气长达三周，促进生长因子表达以维持细胞内氧水平，并支持 CDCs 的存活和增殖。此外，通过体内动物实验研究了该干细胞移植系统对糖尿病足小鼠模型中伤口愈合的影响。移植系统内的释氧微球在损伤组织的缺氧环境中维持了 CDCs 的细胞内氧水平。通过抑制炎症因子的表达和刺激相关生长因子的上调，改善了小鼠背部溃疡组织的血管化，并加速了伤口部位的愈合。总的来说，本研究基于含有 CDCs 和释氧微球的水凝胶的干细胞移植系统，为临床实施局部干细胞输送以改善糖尿病足伤口愈合提供了一种有前途的策略。
