Distribution and differentiation of mesenchymal stem cells in tumor tissue

Background Tumor has an ablity to bcome enriched in mesenchymal stem cells（MSCs）and of guiding MSCs toroun umor as an ecome enr mesenc ma em ce an gulmiarate to tumor tissue.But there are lack of relevant reports on the distribution and differentiatIon Of MSCs in tumortissue and the effect on tumor qrowth after MSCs engrafted in tumor tissue.in this Study,we Observed the dist ribution Ofbone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction Oflocal tumor microenvironment.Methods Twenty-four New Zealand rabbits were randomly classified into the control group and the test group.MSCswere isolated and cultured for each animal.vx-2 tumor tissue was transplanted under the bIadder mucosa Of each animalOne week after the transplantation,the self F2 passage MSCs marked by 4’,6-diamidino-2-phenylindOle weretransplanted into tumor tissue in the test group while only Dulbecco’s modified Eagle’s medium-lOw gIucose was infusedinto the control qroup.Ultrasonoqraphy was performed for each animal 1,2,3 and 4 week（s）affer the vx-2 tumor masswas transplanted.The maximum bladder tumor diameter of each animal was recorded and the mean vaIue Of each groupwas calculated.One animal from each group was sacrificed in the third week and the remaining animaIs in the fou rthweek to Observe the tumor development.Another animal treated the same as the test group waS sacrificed tO Obsen,ethe distribution of MSCs in tumor tissue one week after self MSCS transplantation.lmmunofluorescence was used totrace MSCs in tumor tissue.The double labeling immunofluorescence for a-smooth muscle actin（a-SMA）and vimentinwas performed to identify whether the MSCs can differentiate into myofibroblast.Results The ultrasonoqraphv showed no tumor mass one week after the vx-2 tumor mass transplantation.The meanmaximum tumor diameter of the control qroup and test group was（0.70±0.14）cm and（O.78±0.14）cm,respectively,andthere was no siginificant difference（t=1.308,P=0.204）.The tumor growth rate of the test group increased gradually in thethird and fourth weeks.and the difference of the mean maximum tumor diameter between the two groups also increasedqraduallv and was statlsticallv siginificant（P<O.05）.MSCs dist ributed uniformly in tumor tissue one week aftertransplantation while most were distributed in the tumor stroma three weeks after transplantation.The double labelinqimmunofluorescence showed that the expression of a-SMA as well as Vimentin increased significantly three weeks aftermesenchvmal stem cells engrafted into tumor,indicatln.q that MSCs had differentiated into myofibroblasts under theinduction of the tumor microenvironment.Conclusion MSCs can accelerate the tumor develOpment and can differentiate into myofibroblast under the inductionof tumor microenvironment.