Mouse embryonic stem cell transplantation for treatment of osteoporosis

doi:10.3969/j.issn.2095-4344.2015.06.013

Abstract

Abstract:

BACKGROUND: Because of poor therapeutic effects of drug treatment, stem cell transplantation has become a hot spot in the treatment of osteoporosis.
OBJECTIVE: To investigate the therapeutic efficacy of embryonic stem cell transplantation in the treatment of estrogen deficiency-induced osteoporosis.
METHODS: Thirty female healthy C57BL/6 mice were randomly divided into model, sham-operated, and treatment groups, with 10 mice in each group. Ovariectomized models were established. In the treatment group, embryonic stem cells were injected by tail vein at 1 day after modeling, and there was no treatment in the other two groups. After 10 hours of treatment, flow cytometry was used to detect the apoptosis of T-lymphocytes; after 3 days of treatment, ELISA assay was used to detect the level of tumor necrosis factor-α in mouse serum; after
1 month of treatment, micro-CT was employed to determine the number of bone trabeculae and bone mineral density.
RESULTS AND CONCLUSION: Compared with the sham-operated group, the number of bone trabeculae and bone mineral density were lower in the model group, while the serum level of tumor necrosis factor-α was higher in the model group. After embryonic stem cell transplantation via the tail vein, the number of bone trabeculae and the bone volume fraction were increased certainly, the serum level of umor necrosis factor-α was decreased, and the number of apoptotic T-lymphocytes was increased in the treatment group, which significantly differed from those in the model group (P < 0.05). These findings indicate that embryonic stem cell therapy has a certain effect on the treatment of osteoporosis, which may play a role through immune 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

全文链接：

Key words: Embryonic Stem Cells, Osteoporosis, T-Lymphocytes, Tumor Necrosis Factor-alpha

CLC Number:

R394.2

Fan Zhi-gang, Wang Dong. Mouse embryonic stem cell transplantation for treatment of osteoporosis[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(6): 898-902.

Figures/Tables 3

References

[1] Rossant J.Stem cells from the Mammalian blastocyst.Stem Cells. 2001;19(6):477-482.
[2] Pal R.Embryonic stem (ES) cell-derived cardiomyocytes: a good candidate for cell therapy applications.Cell Biol Int. 2009; 33(3):325-336.
[3] Hipp J, Atala A.Sources of stem cells for regenerative medicine. Stem Cell Rev. 2008;4(1):3-11.
[4] Ganji MR.Postmenopausal osteoporosis treatment and risk of urinary calculus development.Iran J Kidney Dis. 2013;7(3): 171-174.
[5] Wood CL, Wood AM, Harker C,et al.Bone mineral density and osteoporosis after preterm birth: the role of early life factors and nutrition.Int J Endocrinol. 2013;2013:902513.
[6] Avsar U, Karakus E, Halici Z, et al.Prevention of bone loss by Panax ginseng in a rat model of inflammation-induced bone loss.Cell Mol Biol (Noisy-le-grand). 2013;59Suppl:OL1835- 1841.
[7] Yang N, Wang G, Hu C,et al.Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis.J Bone Miner Res. 2013;28(3):559-573.
[8] Reid IR.Osteoporosis treatment: focus on safety.Eur J Intern Med. 2013;24(8):691-697.
[9] 郭志林,王新庄,王木,等.影响昆明小鼠和BALB/C小鼠胚胎干细胞分离、克隆、传代的若干因素[J].中国兽医学报,2006,26(4): 448-450.
[10] 李恩书,彭新荣,钱其军.无血清条件下LIF对小鼠胚胎干细胞增殖及多能性的影响[J].浙江理工大学学报,2011,28(1):96-100.
[11] Li Z, Fei T, Zhang J, et al.BMP4 Signaling Acts via dual-specificity phosphatase 9 to control ERK activity in mouse embryonic stem cells.Cell Stem Cell. 2012;10(2): 171-182.
[12] Liao L, Yang X, Su X,et al.Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow.Cell Death Dis. 2013;4:e600.
[13] Reid IR.Osteoporosis treatment: focus on safety.Eur J Intern Med. 2013;24(8):691-697.
[14] Rachner TD, Khosla S, Hofbauer LC.Osteoporosis: now and the future.Lancet. 2011;377(9773):1276-1287.
[15] Clines GA.Prospects for osteoprogenitor stem cells in fracture repair and osteoporosis.Curr Opin Organ Transplant. 2010; 15(1):73-78.
[16] 滕晓英,王连唐.破骨细胞功能调控与骨质疏松症[J].中国病理生理杂志,2002,18(8):1012-1015.
[17] Cenci S, Toraldo G, Weitzmann MN,et al.Estrogen deficiency induces bone loss by increasing T cell proliferation and lifespan through IFN-gamma-induced class II transactivator. Proc Natl Acad Sci U S A. 2003;100(18): 10405-10410.
[18] Bruserud O, Hamann W, Patel S, et al. IFN-gamma and TNF-alpha secretion by CD4+ and CD8+ TCR alpha beta + T-cell clones derived early after allogeneic bone marrow transplantation.Eur J Haematol. 1993;51(2):73-79.
[19] Kovacic N, Grcevic D, Katavic V, et al.Fas receptor is required for estrogen deficiency-induced bone loss in mice.Lab Invest. 2010;90(3):402-413.
[20] Benisch P, Schilling T, Klein-Hitpass L,et al.The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.PLoS One. 2012;7(9):e45142.
[21] Flores R, Shi J, Fuhrman B,et al.Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: a cross-sectional study.J Transl Med. 2012;10:253.
[22] Katsumoto K, Shiraki N, Miki R, et al.Embryonic and adult stem cell systems in mammals: ontology and regulation..Dev Growth Differ. 2010;52(1):115-129.
[23] He XW, He XS, Lian L,et al.Systemic infusion of bone marrow-derived mesenchymal stem cells for treatment of experimental colitis in mice.Dig Dis Sci. 2012;57(12): 3136-3144.
[24] Maumus M, Guérit D, Toupet K,et al.Mesenchymal stem cell-based therapies in regenerative medicine: applications in rheumatology.Stem Cell Res Ther. 2011;2(2):14