CSCI hydrogel promote adipose derived mesenchymal stem cells in renal ischemia reperfusion injury mice / 中华泌尿外科杂志

ABSTRACT

Objective To explored the therapeutic benefit and safety of acute kidney injury ( AKI) mice induced by ischemia/reperfusion ( I/R ) treating by thermosensitive chitosan chloride ( CSCI ) hydrogel, an injectable scaffold for adipose-derived MSCs ( ADMSCs ) delivery.Methods After establishing the rat model of acute kidney injury, all rats were randomly divided into 4 groups: ADMSCs/PBS group, ADMSCs/CSCI group, PBS group and CSCI group.Live/Dead staining was used to evaluate the Cytocompatibility between CSCI hydrogel and ADMSCs, dihydroethidium ( DHE) staining was used to detect the number of ROS in vivo, and bioluminescence imaging ( BLI) was used to track the retention and survival of ( fluc-mrfp) labeled ADMSCs in the rat kidney, respectively.The biocompatibility and biodegradability of CSCI hydrogel in kidney tissue were detected by HE staining.The improvement of renal function was evaluated by detecting the level of serum creatinine and urea nitrogen.Results Live/Dead staining manifested an satisfactory Cytocompatibility between CSCI hydrogel and ADMSCs.CSCI hydrogel can improve the micro-environment of AKI kidney tissue by lowering the level of ROS.In PBS and CSCI groups, the positive rate of DHE staining was 68.8%±8.5% and 38.5%±5.8%( P <0.05 ) , respectively.These suggested that CSCI hydrogels could improve the retention and survival of grafted ADMSCs.In ADMSCs /CSCI hydrogel group, BLI fluorescent signal can be detected on the seventh day and was undetectable on the 21st day.ROI value of BLI signal changed from 38 ×105 p/(s? cm2? sr) on the first day to 8.5 ×105 p/(s? cm2? sr) on the 14th day.In ADMSCs /PBS group, BLI fluorescent signal only can be detected on the seventh day and was undetectable on the 14th day.ROI value of BLI signal changed from 17 ×105 p/( s?cm2? sr) on the first day to 3.3 ×105 p/( s? cm2? sr) on the 14th day.Results detected on the 3th and 28th day suggested that ADMSCs/CSCI hydrogel group , ADMSCs/PBS group and CSCI hydrogel group have a better self-repairing capability than the PBS injection group ( P<0.05 ) .In addition, compared with the ADMSCs /PBS group and CSCI hydrogel group, ADMSCs /CSCI hydrogel group got a lower tissue injury scores (P<0.05).At the 4th week, significant improvement of the renal function was observed in CSCI hydrogels with ADMSCs groups.Conclusions CSCI hydrogel is a very promising cell carrier for the treatment of AKI.