Bone marrow mesenchymal stem cell transplantation for osteoarthritis

doi:10.3969/j.issn.2095-4344.2016.45.014

Abstract

Abstract:

BACKGROUND: As the ability of self-renewal, differentiation and migration into damaged tissues, bone marrow mesenchymal stem cells have been widely used in a variety of diseases.
OBJECTIVE: To explore the therapeutic effect of bone marrow mesenchymal stem cell transplantation on osteoarthritis in rats.
METHODS: Thirty-six Wistar rats were randomly assigned into transplantation, model or control group. osteoarthritis models were established in the transplantation and model groups, followed by tail vein injection of bone marrow mesenchymal stem cells (5×10⁷/kg) or the same volume of normal saline, respectively. Rats in the control group were subjected to no treatment. Four weeks after injection, levels of CD4⁺CD25⁺ regulatory T cells in the spleen, interleukin-17, tumor necrosis factor-α and transforming growth factor-β1 in serum were detected, and arthritis index and the degree of joint swelling were evaluated as well.
RESULTS AND CONCLUSION: Compared with the control group, both arthritis index and degree of joint swelling were increased significantly in the model group (P < 0.05), but these indicators exhibited a remarkable improvement after cell transplantation (P < 0.05). Levels of CD4⁺CD25⁺ regulatory T cells in the spleen in the three groups were ranked as follows: the transplantation group > the control group > the model group. The levels of interleukin-17 and tumor necrosis factor-α in serum in the transplantation group were lower than those in the model group but higher than those in the control group (P < 0.05). Highest level of transforming growth factor-β1 was obtained in the transplantation group, followed by the control group and model group (P < 0.05). To conclude, these findings indicate that bone marrow mesenchymal stem cell transplantation exert therapeutic effects in osteoarthritis rats by immune and cytokine regulation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Bone Marrow, Mesenchymal Stem Cell Transplantation, Osteoarthritis, Interleukin-17, Tumor Necrosis Factor-alpha, Transforming Growth Factor beta1, T-Lymphocytes, Regulatory, Tissue Engineering

CLC Number:

R394.2

Wu Li-hong, Chen Tao, Wang Rui. Bone marrow mesenchymal stem cell transplantation for osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(45): 6782-6787.

Figures/Tables 1

2.1 大鼠骨髓间充质干细胞的形态培养24 h后出现部分细胞贴壁生长(图1A)，培养48 h时细胞呈圆形、多角形或者短棒形，培养第3天时可见部分细胞集落形成，细胞增殖变快，呈纺锤形或者梭形，培养第7天细胞增殖更快，出现大小不等的细胞集落，细胞以纺锤形和多角形为主，集落出现融合，折光性好，培养第12天时，细胞达90%左右融合，基本铺满瓶底(图1B)。传代培养24 h内出现完全贴壁生长，细胞多呈梭形，分布比较均匀，第3代细胞融合呈辐射状或者漩涡状，形态比较均一。 2.2 大鼠骨髓间充质干细胞的鉴定流式细胞仪鉴定结果显示：CD29的阳性表达率为94.12%，CD44的阳性表达率为70.1%，CD45的阳性表达率为9.78%，CD90的阳性表达率为94.57%，表明分离培养的细胞为骨髓间充质干细胞。 2.3 各组大鼠的一般情况各组大鼠在实验期间均存活，未出现死亡现象。 2.4 各组大鼠的关节炎指数和后肢的关节肿胀度由表1可以看出：移植组、模型组和对照组大鼠的关节炎指数比较差异有显著性意义(P < 0.05)，其中模型组大鼠的关节炎指数明显高于对照组(P < 0.05)，表明关节炎模型制备成功；移植组大鼠关节炎指数明显低于模型组(P < 0.05)，表明骨髓间充质干细胞移植对大鼠骨关节炎有一定的治疗作用。由表1可以看出：移植组、模型组和对照组大鼠的后肢关节肿胀度比较差异有显著性意义(P < 0.05)，其中模型组大鼠的后肢关节肿胀度明显高于对照组(P < 0.05)，表明关节炎模型制备成功；移植组大鼠的后肢关节肿胀度明显低于模型组(P < 0.05)，表明骨髓间充质干细胞移植对大鼠骨关节炎有一定的治疗作用。 2.5 各组脾脏CD4+CD25+调节性T细胞水平比较由表2可以看出：移植组、模型组和对照组大鼠脾脏CD4+CD25+调节性T细胞水平比较差异有显著性意义(P < 0.05)，模型组大鼠脾脏CD4+CD25+调节性T细胞水平明显低于对照组(P < 0.05)；移植组大鼠脾脏CD4+ CD25+调节性T细胞水平明显高于模型组(P < 0.05)，移植组大鼠脾脏CD4+CD25+调节性T细胞水平明显高于对照组(P < 0.05)。 2.6 各组大鼠外周血白细胞介素17、肿瘤坏死因子α和转化生长因子β1水平比较由表3可以看出：移植组、模型组和对照组大鼠血清白细胞介素17水平比较差异有显著性意义(P < 0.05)，模型组大鼠血清白细胞介素17水平明显高于对照组(P < 0.05)；移植组大鼠血清白细胞介素17水平明显低于模型组(P < 0.05)，移植组大鼠血清白细胞介素17水平高于对照组(P < 0.05)。移植组、模型组和对照组大鼠血清肿瘤坏死因子α水平比较差异有显著性意义(P < 0.05)，模型组大鼠血清肿瘤坏死因子α水平明显高于对照组(P < 0.05)；移植组大鼠血清肿瘤坏死因子α水平明显低于模型组(P < 0.05)，移植组大鼠血清肿瘤坏死因子α水平高于对照组(P < 0.05)。移植组、模型组和对照组大鼠血清转化生长因子β1水平比较差异有显著性意义(P < 0.05)，模型组大鼠血清转化生长因子β1水平明显低于对照组(P < 0.05)；移植组大鼠血清转化生长因子β1水平明显高于模型组(P < 0.05)，移植组大鼠血清转化生长因子β1水平高于对照组(P < 0.05)。"

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