2023, Vol. 27 ›› Issue (1): 21-27

Effects of hydrogel loaded with human umbilical cord mesenchymal stem cells on diabetic wound repair in mice

Liu Siqi1, Wu Mingrui1, Qiao Lingran1, Xie Liying1, Chen Siyu1, Han Zhibo2, Zuo Lin1, 3   

Abstract: BACKGROUND: There is a lack of effective treatment methods to promote the healing of the skin wounds of diabetic patients. Human umbilical cord mesenchymal stem cells have been proven to have a variety of therapeutic effects on skin regeneration. Injectable hydrogels have good biocompatibility and adjustability, which can improve the effect of stem cell therapy.  
OBJECTIVE: Taking the hydrogel loaded with human umbilical cord mesenchymal stem cells as a starting point, to observe its curative effect on diabetic skin wounds in mice, and explore the possible mechanism of action.
METHODS:   (1) A diabetic model of C57BL/6J mouse was constructed by continuous intraperitoneal injection of streptozotocin solution for 5 days, and the success of the model was evaluated by blood glucose values collected from the tail vein. (2) A mouse back skin injury model was established by using a puncher. The hydrogel group was treated with pure hydrogel. The composite hydrogel group was treated with hydrogel loaded with human umbilical cord mesenchymal stem cells. The control group was treated with the same amount of normal saline. The wound healing was observed on the 7th and 14th days of treatment.  
RESULTS AND CONCLUSION: (1) The skin wound area of mice in the composite hydrogel group and hydrogel group was significantly smaller than that in the control group at 14 days after gum application (P < 0.05). The skin wound area of mice was significantly smaller in the composite hydrogel group than that in the hydrogel group (P < 0.05). (2) Hematoxylin-eosin staining results illustrated that the new granulation tissue in the composite hydrogel group was significantly more than that in the control group and hydrogel group (P < 0.05). (3) Masson’s staining results clarified that the collagen deposition in the composite hydrogel group was significantly increased compared with the control group and hydrogel group (P < 0.05). (4) The results of immunohistochemical CD31 staining confirmed that the number of new microvessels in the skin trauma was significantly higher in the composite hydrogel group than that in the control group and hydrogel group (P < 0.05). (5) The results of immunohistochemical CD45 staining showed that the area of inflammation in the new skin was significantly reduced in the composite hydrogel group compared with the control group and hydrogel group (P < 0.05). (6) The results of immunofluorescence staining and qRT-PCR showed that compared with the control group and hydrogel group, the amount of M2 macrophages and the level of interleukin 10 in the trauma tissue were significantly higher, and the amount of M1 macrophages and the level of interleukin 6 were significantly lower in the composite hydrogel group (P < 0.05). (7) The above results illustrate that the chlorinated chitosan-β-sodium glycerophosphate composite hydrogel loaded with human umbilical cord mesenchymal stem cells can promote the formation of granulation tissue and microvessels on diabetic wounds, reduce inflammatory response, and promote wound repair.
Key words: human umbilical cord mesenchymal stem cell, diabetes, chitosan chloride, hydrogel, macrophage, interleukin 10, interleukin 6, repair