COMPARISON OF TUMOR NECROSIS FACTOR α INDUCED APOPTOSIS BETWEEN SYNOVIUM-DERIVED MESENCHYMAL STEM CELLS AND BONE MARROW MESENCHYMAL STEM CELLS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

OUYANGYi ¹ , WANGPeng ¹ , SONGBin ¹ , HOUJingyi ¹ , CHENZhong ¹ , DENGHaiquan ¹ , SHENHuiyong ¹ , WUYanfeng ² , LIWeiping ¹ ,  YANGRui ¹

1. Department of Orthopedics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou Guangdong, 510120, P. R. China;
2. Center for Biotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou Guangdong, 510120, P. R. China;

Corresponding author：

YANGRui, Email: yangr@mail.sysu.edu.cn

Keywords：

Synovium-derived mesenchymal stem cells; Bone marrow mesenchymal stem cells; Tumor necrosis factor α; Apoptosis

DOI：

10.7507/1002-1892.20160095

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the anti-apoptotic ability of synovium-derived mesenchymal stem cells (SMSCs) by comparing the apoptosis induced by tumor necrosis factor α (TNF-α) between SMSCs and bone marrow mesenchymal stem cells (BMSCs). Method SMSCs and BMSCs were isolated with tissue adhering and density gradient centrifugation respectively, and cells at passages 3-5 were used in further experiments. After immunophenotype identification and differentiation induction, cells were divided into 4 groups. In the experimental groups, apoptosis of SMSCs and BMSCs were induced by 20 ng/mL TNF-α and 10 μg/mL cycloheximide, and cells were cultured in normal culture medium in the control groups. Cellular morphology were observed by inverted phase contrast microscope. After apoptosis induction for 24 hours, cell viability was determined by cell counting kit 8 assay and apoptotic index was detected by flow cytometer. Moreover, the level of Cleaved Caspase-8, 3 were determined by Western blot. Results Both SMSCs and BMSCs accorded with the definition criteria of MSCs according to results of immunophenotype identification and differentiation induction. After apoptosis induction, cells became shrinking and partially floated and cellular morphologies became worse than those in the control groups. After apoptosis induction for 24 hours, cell viabilities of SMSCs and BMSCs in the control groups were both 100%, and no apoptotic cells were observed. However, cell viabilities of SMSCs and BMSCs in the experimental groups were 60.13%±8.63% and 46.55%±10.54% respectively, which were both significantly lower than those in the control groups (P<0.05) , and cell viability in the SMSCs experimental group was significantly higher than that in the BMSCs experimental group (t=3.152, P=0.006) . The apoptotic index was 36.54%±8.63% in the SMSCs experimental group and was 53.77%±11.52% in the BMSCs experimental group, both were significantly higher than the control groups (1.12%±0.24% and 1.35%±0.31%) (P<0.05) . What's more, it was significantly lower in SMSCs experimental group than that in BMSCs experimental group (t=3.785, P=0.001) . Moreover, no expression of Cleaved Caspase-8, 3 was detected in the control groups. But the levels of Cleaved Caspase-8, 3 were significantly enhanced in the experimental groups and they were lower in SMSCs than in BMSCs (t=13.870, P=0.000; t=7.309, P=0.000) . Conclusions TNF-α induced apoptosis is lower in SMSCs than in BMSCs, which means that SMSCs may have stronger anti-apoptosis ability than BMSCs.

Citation： OUYANGYi, WANGPeng, SONGBin, HOUJingyi, CHENZhong, DENGHaiquan, SHENHuiyong, WUYanfeng, LIWeiping, YANGRui. COMPARISON OF TUMOR NECROSIS FACTOR α INDUCED APOPTOSIS BETWEEN SYNOVIUM-DERIVED MESENCHYMAL STEM CELLS AND BONE MARROW MESENCHYMAL STEM CELLS. Chinese Journal of Reparative and Reconstructive Surgery, 2016, 30(4): 473-478. doi: 10.7507/1002-1892.20160095 Copy

1.	Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell, 2015, 16(3) :239-253.
2.	Wang P, Li Y, Huang L, et al. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs:a 20-week clinical trial. Cell Transplant, 2014, 23(10) :1293-1303.
3.	Swanger SA, Neuhuber B, Himes BT, et al. Analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in the spinal cord. Cell Transplant, 2005, 14(10) :775-786.
4.	Leah E. Paediatric rheumatology:RCT of adalimumab supports anti-TNF therapy for juvenile-onset ankylosing spondylitis. Nat Rev Rheumatol, 2012, 8(12) :693.
5.	Závada J, Uher M, Sisol K, et al. A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year:a propensity score-matched cohort study. Ann Rheum Dis, 2016, 75(1) :96-102.
6.	Ghali O, Chauveau C, Hardouin P, et al. TNF-alpha's effects on proliferation and apoptosis in human mesenchymal stem cells depend on RUNX2 expression. J Bone Miner Res, 2010, 25(7) :1616-1626.
7.	Mao J, Lv Z, Zhuang Y. MicroRNA-23a is involved in tumor necrosis factor-α induced apoptosis in mesenchymal stem cells and myocardial infarction. Exp Mol Pathol, 2014, 97(1) :23-30.
8.	符培亮, 丛锐军, 陈松, 等. 滑膜间充质干细胞成纤维软骨分化条件初步探索. 中国修复重建外科杂志, 2015, 29(1) :81-91.
9.	郑伟伟, 杨民, 武成, 等. 滑膜间充质干细胞体内外成骨特性的实验研究. 中国修复重建外科杂志, 2016, 30(1) :102-109.
10.	Zhang Z, Ding Y, Li W, et al. Interleukin-17A-or tumor necrosis factor alpha-mediated increase in proliferation of T cells cocultured with synovium-derived mesenchymal stem cells in rheumatoid arthritis. Arthritis Res Ther, 2013, 15(5) :R169.
11.	Horie M, Sekiya I, Muneta T, et al. Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells, 2009, 27(4) :878-887.
12.	Sekiya I, Muneta T, Horie M, et al. Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects. Clin Orthop Relat Res, 2015, 473(7) :2316-2326.
13.	赵文君, 邢国胜, 于顺禄. 滑膜间充质干细胞及其在组织工程中的应用. 中国修复重建外科杂志, 2011, 25(12) :1504-1507.
14.	Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006, 8(4) :315-317.
15.	Chen TL, Zhu GL, Wang JA, et al. Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways. Int J Clin Exp Med, 2014, 7(12) :4686-4697.
16.	Zhang F, Cui J, Lv B, et al. Nicorandil protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis. Int J Mol Med, 2015, 36(2) :415-423.
17.	Wang FW, Wang Z, Zhang Y, et al. Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro. J Cell Biochem, 2013, 114(10) :2346-2355.
18.	Lemos DR, Babaeijandaghi F, Low M, et al. Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors. Nat Med, 2015, 21(7) :786-794.
19.	Chung H, Vilaysane A, Lau A, et al. NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. Cell Death Differ, 2016.[Epub ahead of print].
20.	Babu D, Soenen SJ, Raemdonck K, et al. TNF-α/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells. Curr Pharm Des, 2012, 18(28) :4414-4425.

1. Kfoury Y, Scadden DT. Mesenchymal cell contributions to the stem cell niche. Cell Stem Cell, 2015, 16(3) :239-253.
2. Wang P, Li Y, Huang L, et al. Effects and safety of allogenic mesenchymal stem cell intravenous infusion in active ankylosing spondylitis patients who failed NSAIDs:a 20-week clinical trial. Cell Transplant, 2014, 23(10) :1293-1303.
3. Swanger SA, Neuhuber B, Himes BT, et al. Analysis of allogeneic and syngeneic bone marrow stromal cell graft survival in the spinal cord. Cell Transplant, 2005, 14(10) :775-786.
4. Leah E. Paediatric rheumatology:RCT of adalimumab supports anti-TNF therapy for juvenile-onset ankylosing spondylitis. Nat Rev Rheumatol, 2012, 8(12) :693.
5. Závada J, Uher M, Sisol K, et al. A tailored approach to reduce dose of anti-TNF drugs may be equally effective, but substantially less costly than standard dosing in patients with ankylosing spondylitis over 1 year:a propensity score-matched cohort study. Ann Rheum Dis, 2016, 75(1) :96-102.
6. Ghali O, Chauveau C, Hardouin P, et al. TNF-alpha's effects on proliferation and apoptosis in human mesenchymal stem cells depend on RUNX2 expression. J Bone Miner Res, 2010, 25(7) :1616-1626.
7. Mao J, Lv Z, Zhuang Y. MicroRNA-23a is involved in tumor necrosis factor-α induced apoptosis in mesenchymal stem cells and myocardial infarction. Exp Mol Pathol, 2014, 97(1) :23-30.
8. 符培亮, 丛锐军, 陈松, 等. 滑膜间充质干细胞成纤维软骨分化条件初步探索. 中国修复重建外科杂志, 2015, 29(1) :81-91.
9. 郑伟伟, 杨民, 武成, 等. 滑膜间充质干细胞体内外成骨特性的实验研究. 中国修复重建外科杂志, 2016, 30(1) :102-109.
10. Zhang Z, Ding Y, Li W, et al. Interleukin-17A-or tumor necrosis factor alpha-mediated increase in proliferation of T cells cocultured with synovium-derived mesenchymal stem cells in rheumatoid arthritis. Arthritis Res Ther, 2013, 15(5) :R169.
11. Horie M, Sekiya I, Muneta T, et al. Intra-articular injected synovial stem cells differentiate into meniscal cells directly and promote meniscal regeneration without mobilization to distant organs in rat massive meniscal defect. Stem Cells, 2009, 27(4) :878-887.
12. Sekiya I, Muneta T, Horie M, et al. Arthroscopic transplantation of synovial stem cells improves clinical outcomes in knees with cartilage defects. Clin Orthop Relat Res, 2015, 473(7) :2316-2326.
13. 赵文君, 邢国胜, 于顺禄. 滑膜间充质干细胞及其在组织工程中的应用. 中国修复重建外科杂志, 2011, 25(12) :1504-1507.
14. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy, 2006, 8(4) :315-317.
15. Chen TL, Zhu GL, Wang JA, et al. Apoptosis of bone marrow mesenchymal stem cells caused by hypoxia/reoxygenation via multiple pathways. Int J Clin Exp Med, 2014, 7(12) :4686-4697.
16. Zhang F, Cui J, Lv B, et al. Nicorandil protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis. Int J Mol Med, 2015, 36(2) :415-423.
17. Wang FW, Wang Z, Zhang Y, et al. Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro. J Cell Biochem, 2013, 114(10) :2346-2355.
18. Lemos DR, Babaeijandaghi F, Low M, et al. Nilotinib reduces muscle fibrosis in chronic muscle injury by promoting TNF-mediated apoptosis of fibro/adipogenic progenitors. Nat Med, 2015, 21(7) :786-794.
19. Chung H, Vilaysane A, Lau A, et al. NLRP3 regulates a non-canonical platform for caspase-8 activation during epithelial cell apoptosis. Cell Death Differ, 2016.[Epub ahead of print].
20. Babu D, Soenen SJ, Raemdonck K, et al. TNF-α/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells. Curr Pharm Des, 2012, 18(28) :4414-4425.

Chinese Journal of Reparative and Reconstructive Surgery

COMPARISON OF TUMOR NECROSIS FACTOR α INDUCED APOPTOSIS BETWEEN SYNOVIUM-DERIVED MESENCHYMAL STEM CELLS AND BONE MARROW MESENCHYMAL STEM CELLS

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