Efficacy Of Transplantation Human Umbilical Cord Mesenchymal Stem Cells For The Treatment Of Cartilage Injury In Rabbits

Objective:Human umbilical cord mesenchymal stem cells(hUCMSCs)have the potential therapeutic value of repairing the injured cartilage.However,the efficacy in transplantating hUCMSCs is still uncertain.This study is to observe the efficacy in transplantating hUCMSCs on rabbits with cartilage injury.Methods:(1)2-month-old New Zealand white rabbits were selected to establish models of cartilage injury in the knee joint.Following successful establishment,animals were assigned to four groups randomly:Blank control group(only received simple injury,no transplantation),hUCMSC transplantation group(underwent hUCMSCs 6×10~6 cells/time×3 times via local injection),Bone Marrow Mesenchymal Stem Cells(BMMSC)group(subjected to local injection 6×10~6cells/time×3 times at 1 week following injury),and normal saline group(local injection 0.3ml/time×3 times at 1 week following injury).The fourth group underwent sham surgery as the normal control.(2)The animals were selected from cell transplantation group at 4,8 weeks following injury.The recovery of cartilage function following transplantation was observed by clinic feature,topological and morphological characteristics,glycosaminoglycan and biomechanical property.Survival,migration,differentiation and inflammatory in injury site were measured by immunohistochemistry.Results:(1)Clinic feature:The features of hydrops,contracture and conglutination were not observed in the injury knee-joint,and the joint activity is normal.After 4weeks of cell transplantation,no significant filling was found in the injury areas of experimental groups.After 8 weeks of cell transplantation,the obvious tissue regeneration was observed in the hUCMSC group and in the BMMSC group,which accounted for about 1/2 and 1/3 of the injury area respectively.(2)Morphological characteristics:In the hUCMSC group,after 4 weeks of cell transplantation,the new born cells in the hUCMSC group were flat,disordered and tightly aligned,and the cytoplasm was slightly dyed.And after 8 weeks of cell transplantation,the cells tended to be round and the cells were loosely arranged,but there was a tendency to arrange the arrangement of normal cells,and the cytoplasmic staining was relatively faded.(3)Immunohistochemistry:In the hUCMSC group,Noticeably the expression of collagen type I was higher and the expression of collagen type II is lower compared with those of the normal group.However,in the BMMSC group,the expression of collagen type I and II were similar to those of the normal group.In addition,the expression of collagen type MMP-13 in the hUCMSC group and the BMMSC group was significantly higher than that of the normal group.(4)Glycosaminoglycan(GAG)content:After 4 weeks of cell transplantation,the levels of GAG in the hUCMSC group was 10 times higher than that of the saline group(P<0.05),and the levels of GAG in the BMMSC group was 8 times higher than that of the saline group(P<0.05).After 8 weeks of cell transplantation,the GAG in the hUCMSC group was 4.5 times higher than that of the saline group(P<0.05),also the GAG in the BMMSC group was 3.5 times higher than that of the saline group(P<0.05).(5)Biomechanical performance:After 4 weeks of cell transplantation,the maximum load in the hUCMSC group and in the BMMSC group was about 2 times of that in the saline group,but was still significantly lower than that in the normal group(P<0.05).After 8 weeks of cell transplantation,the maximum load of the hUCMSC group was about 3 times that of the saline group,and about 2/5 of the normal group(P<0.05),respectively.The maximum load of the BMMSC group was about twice of that in the saline group,about 1/5 of that in the normal group(P<0.05),respectively.Conclusion:The local treatment with transplantation hUCMSC in the injured cartilage can differentiate into chondrocytes and improve the recovery of cartilage function,but the new born tissue is a complex of fibrous cartilage and hyaline cartilage.Transplantation hUCMSCs do not induce severe tumorigenicity and teratogenicity.But the new born tissue appears to immunoreactivity.Therefore,further studies about the hUCMSCs low immunogenicity under suitable local concentration or dose of cell transplantation are also needed.