摘要
目的探讨骨髓间充质干细胞(MSC)进入肿瘤组织后在肿瘤组织中的分布及其在肿瘤局部微环境诱导下能否分化为肌纤维母细胞。方法 24只新西兰兔随机分为实验组与对照组,每只动物抽取骨髓培养成功 MSC 后,移植 vx-2瘤块制作膀胱 vx-2肿瘤动物模型。两组动物移植肿瘤1周后,实验组培养的 F2代自体 MSC 经 DAPI 标记后回输生成的膀胱肿瘤内,对照组则输入 DMEM培养基。两组动物移植 vx-2瘤块后第1、2、3、4周均行 B 超检查1次,记录每只动物肿瘤最大径,计算每组肿瘤最大径平均值。第3周两组各处死1只肿瘤直径最接近各组平均值的动物,第4周处死所有动物。另有1只动物按照实验组的处理方法回输自体 MSC 1周后处死,观察 MSC 在肿瘤中的分布。免疫荧光切片追踪回输的自体 MSC 在肿瘤组织中的分布及其转分化情况。α-SMA、波形蛋白双重标记免疫荧光染色鉴定 MSC 在肿瘤组织中是否转分化为肌纤维母细胞。结果移植肿瘤后第1周两组 B 超检查均未发现肿瘤生成;第2周对照组肿瘤最大径平均为(0.70±0.14)cm,实验组为(0.78±0.14)cm,但两组相比较差异无统计学意义(t=1.308,P=0.204)。第3、4周实验组肿瘤的生长速度逐渐增快,两组肿瘤最大径平均值的差异逐渐增大,且两组相比较,差异均有统计学意义(均 P<0.05)。MSC 回输肿瘤组织后第1周均匀分布于肿瘤组织内,第3周多分布于肿瘤间质内。双重标记免疫荧光染色显示,MSC 回输入肿瘤组织第3周后α-SMA、波形蛋白表达显著增高,表明 MSC 在肿瘤组织中已分化为肌纤维母细胞。结论 MSC 进入肿瘤组织后开始均匀分布于肿瘤组织内,之后分布于肿瘤间质内,并且可以促进肿瘤的生长,在肿瘤局部微环境的诱导下可以分化为肌纤维母细胞。
Objective To study the distribution of bone marrow mesenchymal stem cells （MSCs） in tumor tissue and the possibility of MSCs differentiating into myofibroblast under the induction of local tumor microenvironment. Methods MSC were isolated from 24 New Zealand rabbits, and cultured. Then vx-2 tumor tissue was transplanted under the bladder mucosa of each animal. Then the rabbits were randomly divided into 2 equal groups： control group and test group. One week after the transplantation, the autologous F2 passage MSCs marked by diamino-phenyl-indole （DAPI） were transplanted into the tumor tissue of the test group and DMEM medium was infused into the tumor tissue of the control group. Ultrasonography was performed 1,2, 3, and 4 week（s） after the vx-2 tumor mass was transplanted. The maximum bladder tumor diameters of each animal were recorded and the mean value of each group was calculated. One animal in each group with its tumor diameter closest to the average value of the very group was put to death in the third week and all the left animals were killed in the fourth week to observe the tumor development. Another rabbit underwent same treatment as that in the test group was put to death to observe the distribution of MSCs in the tumor tissue one week after self-MSC transplantation. Immunofluorescence was used to trace the MSCs in the tumor tissue. Double labeling immunofluorescence for α-smooth muscle actin （α-SMA） and vimentin was performed to identify whether MSCs could differentiate into myofibroblasts. Results Ultrasonography showed no tumor mass one week after the vx-2 tumor mass transplantation. In the second week, the meanmaximum tumor diameter of the control group was 0. 70 ±0. 14 cm, not significantly different from that of the test group （0.78 ±0. 14 cm, t = 1. 308, P =0. 204） , however, the mean maximum tumor diameter in the third and fourth weeks of the control group were 1.8 ± 0. 4 cm and 2. 3 ± 0. 6 cm respectively, both significantly shorter than those of the test group （
出处
《中华医学杂志》
CAS
CSCD
北大核心
2007年第33期2361-2364,共4页
National Medical Journal of China
基金
国家自然科学基金(30672104)
关键词
骨髓
干细胞
肿瘤
肌纤维母细胞
Bone marrow
Stem cells
Neoplasms
Myofibroblast
