Distribution and differentiation of mesenchymal stem cells in tumor tissue.
BACKGROUND
Tumor has an ability to become enriched in mesenchymal stem cells (MSCs) and of guiding MSCs to migrate to tumor tissue. But there are lack of relevant reports on the distribution and differentiation of MSCs in tumor tissue and the effect on tumor growth after MSCs engrafted in tumor tissue. In this study, we observed the distribution of bone marrow MSCs in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment.


METHODS
Twenty-four New Zealand rabbits were randomly classified into the control group and the test group. MSCs were isolated and cultured for each animal. vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. One week after the transplantation, the self F2 passage MSCs marked by 4', 6-diamidino-2-phenylindole were transplanted into tumor tissue in the test group while only Dulbecco's modified Eagle's medium-low glucose was infused into the control group. Ultrasonography was performed for each animal 1, 2, 3 and 4 week (s) after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameter of each animal was recorded and the mean value of each group was calculated. One animal from each group was sacrificed in the third week and the remaining animals in the fourth week to observe the tumor development. Another animal treated the same as the test group was sacrificed to observe the distribution of MSCs in tumor tissue one week after self MSCs transplantation. Immunofluorescence was used to trace MSCs in tumor tissue. The double labeling immunofluorescence for alpha-smooth muscle actin (alpha-SMA) and vimentin was performed to identify whether the MSCs can differentiate into myofibroblast.


RESULTS
The ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. The mean maximum tumor diameter of the control group and test group was (0.70 +/- 0.14) cm and (0.78 +/- 0.14) cm, respectively, and there was no significant difference (t = 1.308, P = 0.204). The tumor growth rate of the test group increased gradually in the third and fourth weeks, and the difference of the mean maximum tumor diameter between the two groups also increased gradually and was statistically significant (P < 0.05). MSCs distributed uniformly in tumor tissue one week after transplantation while most were distributed in the tumor stroma three weeks after transplantation. The double labeling immunofluorescence showed that the expression of alpha-SMA as well as Vimentin increased significantly three weeks after mesenchymal stem cells engrafted into tumor, indicating that MSCs had differentiated into myofibroblasts under the induction of the tumor microenvironment.


CONCLUSIONS
MSCs can accelerate the tumor development and can differentiate into myofibroblast under the induction of tumor microenvironment.
Zhao
Hai-Feng
HF
Department of Urology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Chen
Jun
J
Xu
Zhi-Shun
ZS
Zhang
Ke-Qin
KQ