PROGRESS OF INDUCED OSTEOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSFECTED BY DOUBLE-GENE_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

CHENNing ¹ ,  BEIChaoyong ¹ ,  JIANGLinbin ² , SUMou ¹ , XUWei ¹

1. Department of Limb Traumatic Orthopaedics, Guilin Medical College Affiliated Hospital, Guilin Guangxi, 541004, P. R. China;
2. Guilin Medical College Institute of Biotechnology;

Corresponding author：

BEIChaoyong, Email: beichy2008@126.com; JIANGLinbin, Email: 444589396@qq.com

Keywords：

Double-gene transfection; Bone marrow mesenchymal stem cells; Osteogenic induction

DOI：

10.7507/1002-1892.20140333

Video：

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Objective To review the research progress of induced osteogenesis of bone marrow mesenchymal stem cells (BMSCs) transfected by double-gene. Methods The recent literature concerning the comparative research of induced osteogenesis of BMSCs transfected by double-gene was extensively reviewed. The characteristics of BMSCs, the advantage and effect of synergistic inductive osteogenesis, the application prospect and problems of BMSCs transfected by double-gene were summarized. Results The effect of induced osteogenesis concerning BMSCs transfected by double-gene is far superior to single gene transfection and the activity of osteoblast is also significantly increased. The research used in bone tissue engineering experiment also obtain good effect. Conclusion Induced osteogenesis of BMSCs transfected by double-gene is able to make up for the lack of a single gene transfection and has great development prospects in the orthopaedic field.

Citation： CHENNing, BEIChaoyong, JIANGLinbin, SUMou, XUWei. PROGRESS OF INDUCED OSTEOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSFECTED BY DOUBLE-GENE. Chinese Journal of Reparative and Reconstructive Surgery, 2014, 28(12): 1540-1543. doi: 10.7507/1002-1892.20140333 Copy

1.	Sudo K, Kanno M, Miharada K, et al. Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adi pogenic cells in vitro are present in most primary fibroblast-l ike cell populations. Stem Cells, 2007, 25(7):1610-1617.
2.	连真珍, 林绍强. 骨髓间充质干细胞的特性及应用基础研究进展. 中华细胞与干细胞杂志(电子版), 2013, 3(1):22-26.
3.	Mezey E. The therapeutic potential of bone marrow-derived stromal cells. J Cell Biochem, 2011, 112(10):2683-2687.
4.	Khaled EG, Saleh M, Hindocha S, et al. Tissue engineering for bone production-stem cells, gene therapy and scaffolds. Open Orthop J, 2011, 5 Suppl 2:289-295.
5.	Chen L, Tredget EE, Liu C, et al. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One, 2009, 4(9):e7119.
6.	Dash S, Dash NR, Guru B, et al. Towards reaching the target:cl inical application of mesenchymal stem cells for diabetic foot ulcers. Rejuvenation Res, 2014, 17(1):40-53.
7.	Honmou O, Houkin K, Matsunaga T, et al. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain, 2011, 134(Pt 6):1790-1807.
8.	Nakamura A, Akahane M, Shigematsu H, et al. Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model. Bone, 2010, 46(2):418-424.
9.	Loffredo FS, Steinhauser ML, Gannon J, et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell, 2011, 8(4):389-398.
10.	Zhou H, Guo M, Bian C, et al. Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graftversus-host disease:cl inical report. Biol Blood Marrow Transplant, 2010, 16(3):403-412.
11.	Petrini M, Pacini S, Trombi L, et al. Identification and purification of mesodermal progenitor cells from human adult bone marrow. Stem Cells Dev, 2009, 18(6):857-866.
12.	Klopp AH, Gupta A, Spaeth E, et al. Concise review:Dissecting a discrepancy in the literature:do mesenchymal stem cells support or suppress tumor growth? Stem Cells, 2011, 29(1):11-19.
13.	刘广鹏, 李宇琳, 孙剑, 等. 成骨诱导的人骨髓基质干细胞生物安全性评价. 组织工程与重建外科杂志, 2008, 4(4):181-184.
14.	Suzuki D, Yamada A, Amano T, et al. Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development. Dev Biol, 2009, 335(2):396-406.
15.	Rosen V. BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev, 2009, 20(5-6):475-480.
16.	Wang Q, Huang C, Xue M, et al. Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing. Bone, 2011, 48(3):524-532.
17.	Shen B, Wei A, Whittaker S, et al. The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multi potent mesenchymal stromal cells in vitro. J Cell Biochem, 2010, 109(2):406-416.
18.	Zhu L, Chuanchang D, Wei L, et al. Enhanced healing of goat femurdefect using BMP7 gene-modified BMSCs and load-bearing tissueengineered bone. J Orthop Res, 2010, 28(3):412-418.
19.	Qing W, Guang-Xing C, Lin G, et al. The osteogenic study of tissue engineering bone with BMP2 and BMP7 gene-modified rat adi posederived stem cell. J Biomed Biotechnol, 2012, 2012:410879.
20.	Bustos-Valenzuela JC, Fujita A, Halcsik E, et al. Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells. BMC Res Notes, 2011, 4:370.
21.	Ishijima M, Suzuki N, Hozumi K, et al. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol, 2012, 31(4):234-245.
22.	Liu B, Li X, Liang G, et al. VEGF expression in mesenchymal stem cells promotes bone formation of tissue-engineered bones. Mol Med Rep, 2011, 4(6):1121-1126.
23.	Ramazanoglu M, Lutz R, Rusche P, et al. Bone response to biomimetic implants del ivering BMP-2 and VEGF:an immunohistochemical study. J Craniomaxillofac Surg, 2013, 41(8):826-835.
24.	Xiao C, Zhou H, Liu G, et al. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration. Biomed Mater, 2011, 6(1):015013.
25.	Sporn MB, Roberts AB, Wakefield LM, et al. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol, 1987, 105(3):1039-1045.
26.	Patil AS, Sable RB, Kothari RM. An update on transforming growth factor-beta (TGF-beta):sources, types, functions and cl inical applicabil ity for cartilage/bone heal ing. J Cell Physiol, 2011, 226(12):3094-3103.
27.	Chen G, Deng C, Li YP. TGF-beta and BMP signal ing in osteoblast differentiation and bone formation. Int J Biol Sci, 2012, 8(2):272-288.
28.	Kuroda S, Sumner DR, Virdi AS. Effects of TGF-beta1 and VEGF-A transgenes on the osteogenic potential of bone marrow stromal cells in vitro and in vivo. J Tissue Eng, 2012, 3(1):2041731412459745.
29.	Yakar S, Courtland HW, Clemmons D. IGF-1 and bone:New discoveries from mouse models. J Bone Miner Res, 2010, 25(12):2543-2552.
30.	Xian L, Wu X, Pang L, et al. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med, 2012, 18(7): 1095-1101.
31.	An C, Cheng Y, Yuan Q, et al. IGF-1 and BMP-2 induces differentiation of adi pose-derived mesenchymal stem cells into chondrocytesl ike cells. Ann Biomed Eng, 2010, 38(4):1647-1654.
32.	Chen L, Jiang W, Huang J, et al. Insulin-l ike growth factor 2(IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res, 2010, 25(11):2447-2459.
33.	Greenhalgh DG, Sprugel KH, Murray MJ, et al. PDGF and FGF stimulate wound heal ing in the genetically diabetic mouse. Am J Pathol, 1990, 136(6):1235-1246.
34.	Xiao L, Sobue T, Esl iger A, et al. Disruption of the Fgf2 gene activates the adi pogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells. Bone, 2010, 47(2):360-370.
35.	Hughes-Fulford M, Li CF. The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization. J Orthop Surg Res, 2011, 6:8.
36.	郝伟, 姜明, 周东生, 等. rhBMP-2、bFGF双基因共转染兔骨髓间充质干细胞复合nHA/RHLC/PLA支架及其体内外成骨分化研究. 中国矫形外科杂志, 2011, 19(13):1130-1134.
37.	Shah P, Keppler L, Rutkowski J. A review of platelet derived growth factor playing pivotal role in bone regeneration. J Oral Implantol, 2014, 40(3):330-340.
38.	Caplan AI, Correa D. PDGF in bone formation and regeneration:new insights into a novel mechanism involving MSCs. J Orthop Res, 2011, 29(12):1795-1803.
39.	Zhang Y, Cheng N, Miron R, et al. Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials, 2012, 33(28):6698-6708.
40.	Fierro FA, Kalomoiris S, Sondergaard CS, et al. Effects on proliferation and differentiation of multi potent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapy. Stem Cells, 2011, 29(11):1727-1737.

1. Sudo K, Kanno M, Miharada K, et al. Mesenchymal progenitors able to differentiate into osteogenic, chondrogenic, and/or adi pogenic cells in vitro are present in most primary fibroblast-l ike cell populations. Stem Cells, 2007, 25(7):1610-1617.
2. 连真珍, 林绍强. 骨髓间充质干细胞的特性及应用基础研究进展. 中华细胞与干细胞杂志(电子版), 2013, 3(1):22-26.
3. Mezey E. The therapeutic potential of bone marrow-derived stromal cells. J Cell Biochem, 2011, 112(10):2683-2687.
4. Khaled EG, Saleh M, Hindocha S, et al. Tissue engineering for bone production-stem cells, gene therapy and scaffolds. Open Orthop J, 2011, 5 Suppl 2:289-295.
5. Chen L, Tredget EE, Liu C, et al. Analysis of allogenicity of mesenchymal stem cells in engraftment and wound healing in mice. PLoS One, 2009, 4(9):e7119.
6. Dash S, Dash NR, Guru B, et al. Towards reaching the target:cl inical application of mesenchymal stem cells for diabetic foot ulcers. Rejuvenation Res, 2014, 17(1):40-53.
7. Honmou O, Houkin K, Matsunaga T, et al. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain, 2011, 134(Pt 6):1790-1807.
8. Nakamura A, Akahane M, Shigematsu H, et al. Cell sheet transplantation of cultured mesenchymal stem cells enhances bone formation in a rat nonunion model. Bone, 2010, 46(2):418-424.
9. Loffredo FS, Steinhauser ML, Gannon J, et al. Bone marrow-derived cell therapy stimulates endogenous cardiomyocyte progenitors and promotes cardiac repair. Cell Stem Cell, 2011, 8(4):389-398.
10. Zhou H, Guo M, Bian C, et al. Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graftversus-host disease:cl inical report. Biol Blood Marrow Transplant, 2010, 16(3):403-412.
11. Petrini M, Pacini S, Trombi L, et al. Identification and purification of mesodermal progenitor cells from human adult bone marrow. Stem Cells Dev, 2009, 18(6):857-866.
12. Klopp AH, Gupta A, Spaeth E, et al. Concise review:Dissecting a discrepancy in the literature:do mesenchymal stem cells support or suppress tumor growth? Stem Cells, 2011, 29(1):11-19.
13. 刘广鹏, 李宇琳, 孙剑, 等. 成骨诱导的人骨髓基质干细胞生物安全性评价. 组织工程与重建外科杂志, 2008, 4(4):181-184.
14. Suzuki D, Yamada A, Amano T, et al. Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development. Dev Biol, 2009, 335(2):396-406.
15. Rosen V. BMP2 signaling in bone development and repair. Cytokine Growth Factor Rev, 2009, 20(5-6):475-480.
16. Wang Q, Huang C, Xue M, et al. Expression of endogenous BMP-2 in periosteal progenitor cells is essential for bone healing. Bone, 2011, 48(3):524-532.
17. Shen B, Wei A, Whittaker S, et al. The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multi potent mesenchymal stromal cells in vitro. J Cell Biochem, 2010, 109(2):406-416.
18. Zhu L, Chuanchang D, Wei L, et al. Enhanced healing of goat femurdefect using BMP7 gene-modified BMSCs and load-bearing tissueengineered bone. J Orthop Res, 2010, 28(3):412-418.
19. Qing W, Guang-Xing C, Lin G, et al. The osteogenic study of tissue engineering bone with BMP2 and BMP7 gene-modified rat adi posederived stem cell. J Biomed Biotechnol, 2012, 2012:410879.
20. Bustos-Valenzuela JC, Fujita A, Halcsik E, et al. Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells. BMC Res Notes, 2011, 4:370.
21. Ishijima M, Suzuki N, Hozumi K, et al. Perlecan modulates VEGF signaling and is essential for vascularization in endochondral bone formation. Matrix Biol, 2012, 31(4):234-245.
22. Liu B, Li X, Liang G, et al. VEGF expression in mesenchymal stem cells promotes bone formation of tissue-engineered bones. Mol Med Rep, 2011, 4(6):1121-1126.
23. Ramazanoglu M, Lutz R, Rusche P, et al. Bone response to biomimetic implants del ivering BMP-2 and VEGF:an immunohistochemical study. J Craniomaxillofac Surg, 2013, 41(8):826-835.
24. Xiao C, Zhou H, Liu G, et al. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration. Biomed Mater, 2011, 6(1):015013.
25. Sporn MB, Roberts AB, Wakefield LM, et al. Some recent advances in the chemistry and biology of transforming growth factor-beta. J Cell Biol, 1987, 105(3):1039-1045.
26. Patil AS, Sable RB, Kothari RM. An update on transforming growth factor-beta (TGF-beta):sources, types, functions and cl inical applicabil ity for cartilage/bone heal ing. J Cell Physiol, 2011, 226(12):3094-3103.
27. Chen G, Deng C, Li YP. TGF-beta and BMP signal ing in osteoblast differentiation and bone formation. Int J Biol Sci, 2012, 8(2):272-288.
28. Kuroda S, Sumner DR, Virdi AS. Effects of TGF-beta1 and VEGF-A transgenes on the osteogenic potential of bone marrow stromal cells in vitro and in vivo. J Tissue Eng, 2012, 3(1):2041731412459745.
29. Yakar S, Courtland HW, Clemmons D. IGF-1 and bone:New discoveries from mouse models. J Bone Miner Res, 2010, 25(12):2543-2552.
30. Xian L, Wu X, Pang L, et al. Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells. Nat Med, 2012, 18(7): 1095-1101.
31. An C, Cheng Y, Yuan Q, et al. IGF-1 and BMP-2 induces differentiation of adi pose-derived mesenchymal stem cells into chondrocytesl ike cells. Ann Biomed Eng, 2010, 38(4):1647-1654.
32. Chen L, Jiang W, Huang J, et al. Insulin-l ike growth factor 2(IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res, 2010, 25(11):2447-2459.
33. Greenhalgh DG, Sprugel KH, Murray MJ, et al. PDGF and FGF stimulate wound heal ing in the genetically diabetic mouse. Am J Pathol, 1990, 136(6):1235-1246.
34. Xiao L, Sobue T, Esl iger A, et al. Disruption of the Fgf2 gene activates the adi pogenic and suppresses the osteogenic program in mesenchymal marrow stromal stem cells. Bone, 2010, 47(2):360-370.
35. Hughes-Fulford M, Li CF. The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization. J Orthop Surg Res, 2011, 6:8.
36. 郝伟, 姜明, 周东生, 等. rhBMP-2、bFGF双基因共转染兔骨髓间充质干细胞复合nHA/RHLC/PLA支架及其体内外成骨分化研究. 中国矫形外科杂志, 2011, 19(13):1130-1134.
37. Shah P, Keppler L, Rutkowski J. A review of platelet derived growth factor playing pivotal role in bone regeneration. J Oral Implantol, 2014, 40(3):330-340.
38. Caplan AI, Correa D. PDGF in bone formation and regeneration:new insights into a novel mechanism involving MSCs. J Orthop Res, 2011, 29(12):1795-1803.
39. Zhang Y, Cheng N, Miron R, et al. Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials, 2012, 33(28):6698-6708.
40. Fierro FA, Kalomoiris S, Sondergaard CS, et al. Effects on proliferation and differentiation of multi potent bone marrow stromal cells engineered to express growth factors for combined cell and gene therapy. Stem Cells, 2011, 29(11):1727-1737.

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PROGRESS OF INDUCED OSTEOGENESIS OF BONE MARROW MESENCHYMAL STEM CELLS TRANSFECTED BY DOUBLE-GENE

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