The application of urine derived stem cells in regeneration of musculoskeletal system_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

XING Fei , LIU Guoming , DUAN Xin ,  XIANG Zhou

Department of Orthopedics, West China Hospital, Sichuan University, Chengdu Sichuan, 610041, P.R.China;

Corresponding author：

XIANG Zhou, Email: xiangzhou15@hotmail.com

Keywords：

Urine derived stem cells; tissue engineering; multi-differentiation; induced pluripotent stem cells; bone repair

DOI：

10.7507/1002-1892.201804024

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the application of urine derived stem cells (USCs) in regeneration of musculoskeletal system. Methods The original literature about USCs in the regeneration of musculoskeletal system was extensively reviewed and analyzed. Results The source of USCs is noninvasive and extensive. USCs express MSCs surface markers with stable proliferative and multi-directional differentiation capabilities, and are widely used in bone, skin, nerve, and other skeletal and muscle system regeneration fields and show a certain repair capacity. Conclusion USCs from non-invasive sources have a wide application prospect in the regeneration of musculoskeletal system, but the definite biological mechanism of its repair needs further study.

Citation： XING Fei, LIU Guoming, DUAN Xin, XIANG Zhou. The application of urine derived stem cells in regeneration of musculoskeletal system. Chinese Journal of Reparative and Reconstructive Surgery, 2018, 32(11): 1477-1482. doi: 10.7507/1002-1892.201804024 Copy

1.	Fu WL, Xiang Z, Huang FG, et al. Coculture of peripheral blood-derived mesenchymal stem cells and endothelial progenitor cells on strontium-doped calcium polyphosphate scaffolds to generate vascularized engineered bone. Tissue Eng Part A, 2014, 21(5-6): 948-959.
2.	Bharadwaj S, Liu G, Shi Y, et al. Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology. Stem Cells, 2013, 31(9): 1840-1856.
3.	Sutherland GR, Bain AD. Culture of cells from the urine of newborn children. Nature, 1972, 239(5369): 231.
4.	Racusen LC, Fivush BA, Andersson H, et al. Culture of renal tubular cells from the urine of patients with nephropathic cystinosis. J Am Soc Nephrol, 1991, 1(8): 1028-1033.
5.	Zhang Y, McNeill E, Tian H, et al. Urine derived cells are a potential source for urological tissue reconstruction. J Urol, 2008, 180(5): 2226-2233.
6.	Bharadwaj S, Liu G, Shi Y, et al. Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng Part A, 2011, 17(15-16): 2123-2132.
7.	Chun SY, Kim HT, Lee JS, et al. Characterization of urine-derived cells from upper urinary tract in patients with bladder cancer. Urology, 2012, 79(5): 1186. e1-e7.
8.	Schosserer M, Reynoso R, Wally V, et al. Urine is a novel source of autologous mesenchymal stem cells for patients with epidermolysis bullosa. BMC Res Notes, 2015, 8: 767.
9.	Gao P, Han P, Jiang D, et al. Effects of the donor age on proliferation, senescence and osteogenic capacity of human urine-derived stem cells. Cytotechnology, 2017, 69(5): 751-763.
10.	Lang R, Liu G, Shi Y, et al. Self-renewal and differentiation capacity of urine-derived stem cells after urine preservation for 24 hours. PLoS One, 2013, 8(1): e53980.
11.	汪泱, 关俊杰, 邓志锋, 等. 尿液间充质干细胞的提取及扩增培养方法和应用. 中国: CN201210470118. 1. 2013-02-13.
12.	陈春媛, 牛鑫, 汪泱. 尿液源性干细胞的研究进展. 中国修复重建外科杂志, 2015, 29(3): 372-376.
13.	Zhang D, Wei G, Li P, et al. Urine-derived stem cells: A novel and versatile progenitor source for cell-based therapy and regenerative medicine. Genes Dis, 2014, 1(1): 8-17.
14.	Okamoto T, Sasaki S, Yamazaki T, et al. Prevalence of CD44-positive glomerular parietal epithelial cells reflects podocyte injury in adriamycin nephropathy. Nephron Exp Nephrol, 2013, 124(3-4): 11-18.
15.	Tian SF, Jiang ZZ, Liu YM, et al. Human urine-derived stem cells contribute to the repair of ischemic acute kidney injury in rats. Mol Med Rep, 2017, 16(4): 5541-5548.
16.	Chen X, Chen R, Wei W, et al. PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res, 2018.[Epub ahead of print].
17.	Gu C, Xie F, Zhang B, et al. High glucose promotes epithelial-mesenchymal transition of uterus endometrial cancer cells by increasing ER/GLUT4-mediated VEGF secretion. Cell Physiol Biochem, 2018, 50(2): 706-720.
18.	Yaoita E, Yoshida Y. Polygonal epithelial cells in glomerular cell culture: Podocyte or parietal epithelial origin? Microsc Res Tech, 2002, 57(4): 212-216.
19.	Liu G, Pareta RA, Wu R, et al. Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. Biomaterials, 2013, 34(4): 1311-1326.
20.	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.
21.	Guan JJ, Niu X, Gong FX, et al. Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology. Tissue Eng Part A, 2014, 20(13-14): 1794-1806.
22.	Pei M, Li J, Zhang Y, et al. Expansion on a matrix deposited by nonchondrogenic urine stem cells strengthens the chondrogenic capacity of repeated-passage bone marrow stromal cells. Cell Tissue Res, 2014, 356(2): 391-403.
23.	Kang HS, Choi SH, Kim BS, et al. Advanced properties of urine derived stem cells compared to adipose tissue derived stem cells in terms of cell proliferation, immune modulation and multi differentiation. J Korean Med Sci, 2015, 30(12): 1764-1776.
24.	Shi Y, Liu G, Shantaram B, et al. 736 Urine derived stem cells with high telomerase activity for cell based therapy in urology. Journal of Urology, 2012, 187(4): e302.
25.	Tian H, Bharadwaj S, Liu Y, et al. Differentiation of human bone marrow mesenchymal stem cells into bladder cells: potential for urological tissue engineering. Tissue Eng Part A, 2010, 16(5): 1769-1779.
26.	Zhang Y, Lin HK, Frimberger D, et al. Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int, 2005, 96(7): 1120-1125.
27.	Guan J, Zhang J, Guo S, et al. Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/β-catenin signaling pathway. Biomaterials, 2015, 55: 1-11.
28.	Guan J, Zhang J, Zhu Z, et al. Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells. Stem Cell Res Ther, 2015, 6: 5.
29.	Kim SW, Jung JH, Lamsal K, et al. Antifungal effects of silver nanoparticles (AgNPs) against various plant pathogenic fungi. Mycobiology, 2012, 40(1): 53-58.
30.	Qin H, Zhu C, An Z, et al. Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations. Int J Nanomedicine, 2014, 9: 2469-2478.
31.	Guan J, Zhang J, Li H, et al. Human urine derived stem cells in combination with β-TCP can be applied for bone regeneration. PLoS One, 2015, 10(5): e0125253.
32.	Huang BJ, Hu JC, Athanasiou KA. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials, 2016, 98: 1-22.
33.	Zhao Z, Zhou X, Guan J, et al. Co-implantation of bone marrow mesenchymal stem cells and chondrocytes increase the viability of chondrocytes in rat osteo-chondral defects. Oncol Lett, 2018, 15(5): 7021-7027.
34.	Chen L, Li L, Xing F, et al. Human urine-derived stem cells: potential for cell-based therapy of cartilage defects. Stem Cells Int, 2018, 2018: 4686259.
35.	Fu Y, Guan J, Guo S, et al. Human urine-derived stem cells in combination with polycaprolactone/gelatin nanofibrous membranes enhance wound healing by promoting angiogenesis. J Transl Med, 2014, 12: 274.
36.	Dong X, Chang J, Li H. Bioglass promotes wound healing through modulating the paracrine effects between macrophages and repairing cells. Journal of Materials Chemistry B, 2017, 26: 5.
37.	Zhang Y, Niu X, Dong X, et al. Bioglass enhanced wound healing ability of urine-derived stem cells through promoting paracrine effects between stem cells and recipient cells. J Tissue Eng Regen Med, 2018, 12(3): e1609-e1622.
38.	Hu G, Drescher KM, Chen XM. Exosomal miRNAs: biological properties and therapeutic potential. Front Genet, 2012, 3: 56.
39.	Chen CY, Rao SS, Ren L, et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 2018, 8(6): 1607-1623.
40.	Chen W, Xie M, Yang B, et al. Skeletal myogenic differentiation of human urine-derived cells as a potential source for skeletal muscle regeneration. J Tissue Eng Regen Med, 2017, 11(2): 334-341.
41.	Kim EY, Page P, Dellefave-Castillo LM, et al. Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease. Skelet Muscle, 2016, 6: 32.
42.	Yang Q, Chen X, Zheng T, et al. Transplantation of human urine-derived stem cells transfected with pigment epithelium-derived factor to protect erectile function in a rat model of cavernous nerve injury. Cell Transplant, 2016, 25(11): 1987-2001.
43.	Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol, 2008, 26(1): 101-106.
44.	Zhao XY, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation. Nature, 2009, 461(7260): 86-90.
45.	Stadtfeld M, Maherali N, Breault DT, et al. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell, 2008, 2(3): 230-240.
46.	Zhang SZ, Li HF, Ma LX, et al. Urine-derived induced pluripotent stem cells as a modeling tool for paroxysmal kinesigenic dyskinesia. Biol Open, 2015, 4(12): 1744-1752.
47.	Afzal MZ, Strande JL. Generation of induced pluripotent stem cells from muscular dystrophy patients: efficient integration-free reprogramming of urine derived cells. J Vis Exp, 2015, (95): 52032.
48.	Wang L, Li X, Huang W, et al. TGFβ signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells. Sci Rep, 2016, 6: 22484.
49.	M Lee Y, Zampieri BL, Scott-McKean JJ, et al. Generation of integration-free induced pluripotent stem cells from urine-derived cells isolated from individuals with down syndrome. Stem Cells Transl Med, 2017, 6(6): 1465-1476.
50.	Aboushady IM, Salem ZA, Sabry D, et al. Comparative study of the osteogenic potential of mesenchymal stem cells derived from different sources. J Clin Exp Dent, 2018, 10(1): e7-e13.
51.	Fernandes M, Valente SG, Sabongi RG, et al. Bone marrow-derived mesenchymal stem cells. Neural Regen Res, 2018, 13(1): 100-104.
52.	Hakki SS, Turaç G, Bozkurt SB, et al. Comparison of different sources of mesenchymal stem cells: palatal versus lipoaspirated adipose tissue. Cells Tissues Organs, 2017, 204(5-6): 228-240.
53.	Amiri F, Molaei S, Bahadori M, et al. Autophagy-modulated human bone marrow-derived mesenchymal stem cells accelerate liver restoration in mouse models of acute liver failure. Iran Biomed J, 2016, 20(3): 135-144.
54.	Jung J, Choi JH, Lee Y, et al. Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4-injured rat liver model via increased autophagic mechanism. Stem Cells, 2013, 31(8): 1584-1596.
55.	Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 2008, 3(3): 301-313.

1. Fu WL, Xiang Z, Huang FG, et al. Coculture of peripheral blood-derived mesenchymal stem cells and endothelial progenitor cells on strontium-doped calcium polyphosphate scaffolds to generate vascularized engineered bone. Tissue Eng Part A, 2014, 21(5-6): 948-959.
2. Bharadwaj S, Liu G, Shi Y, et al. Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology. Stem Cells, 2013, 31(9): 1840-1856.
3. Sutherland GR, Bain AD. Culture of cells from the urine of newborn children. Nature, 1972, 239(5369): 231.
4. Racusen LC, Fivush BA, Andersson H, et al. Culture of renal tubular cells from the urine of patients with nephropathic cystinosis. J Am Soc Nephrol, 1991, 1(8): 1028-1033.
5. Zhang Y, McNeill E, Tian H, et al. Urine derived cells are a potential source for urological tissue reconstruction. J Urol, 2008, 180(5): 2226-2233.
6. Bharadwaj S, Liu G, Shi Y, et al. Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng Part A, 2011, 17(15-16): 2123-2132.
7. Chun SY, Kim HT, Lee JS, et al. Characterization of urine-derived cells from upper urinary tract in patients with bladder cancer. Urology, 2012, 79(5): 1186. e1-e7.
8. Schosserer M, Reynoso R, Wally V, et al. Urine is a novel source of autologous mesenchymal stem cells for patients with epidermolysis bullosa. BMC Res Notes, 2015, 8: 767.
9. Gao P, Han P, Jiang D, et al. Effects of the donor age on proliferation, senescence and osteogenic capacity of human urine-derived stem cells. Cytotechnology, 2017, 69(5): 751-763.
10. Lang R, Liu G, Shi Y, et al. Self-renewal and differentiation capacity of urine-derived stem cells after urine preservation for 24 hours. PLoS One, 2013, 8(1): e53980.
11. 汪泱, 关俊杰, 邓志锋, 等. 尿液间充质干细胞的提取及扩增培养方法和应用. 中国: CN201210470118. 1. 2013-02-13.
12. 陈春媛, 牛鑫, 汪泱. 尿液源性干细胞的研究进展. 中国修复重建外科杂志, 2015, 29(3): 372-376.
13. Zhang D, Wei G, Li P, et al. Urine-derived stem cells: A novel and versatile progenitor source for cell-based therapy and regenerative medicine. Genes Dis, 2014, 1(1): 8-17.
14. Okamoto T, Sasaki S, Yamazaki T, et al. Prevalence of CD44-positive glomerular parietal epithelial cells reflects podocyte injury in adriamycin nephropathy. Nephron Exp Nephrol, 2013, 124(3-4): 11-18.
15. Tian SF, Jiang ZZ, Liu YM, et al. Human urine-derived stem cells contribute to the repair of ischemic acute kidney injury in rats. Mol Med Rep, 2017, 16(4): 5541-5548.
16. Chen X, Chen R, Wei W, et al. PRMT5 circular RNA promotes metastasis of urothelial carcinoma of the bladder through sponging miR-30c to induce epithelial-mesenchymal transition. Clin Cancer Res, 2018.[Epub ahead of print].
17. Gu C, Xie F, Zhang B, et al. High glucose promotes epithelial-mesenchymal transition of uterus endometrial cancer cells by increasing ER/GLUT4-mediated VEGF secretion. Cell Physiol Biochem, 2018, 50(2): 706-720.
18. Yaoita E, Yoshida Y. Polygonal epithelial cells in glomerular cell culture: Podocyte or parietal epithelial origin? Microsc Res Tech, 2002, 57(4): 212-216.
19. Liu G, Pareta RA, Wu R, et al. Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. Biomaterials, 2013, 34(4): 1311-1326.
20. 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.
21. Guan JJ, Niu X, Gong FX, et al. Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology. Tissue Eng Part A, 2014, 20(13-14): 1794-1806.
22. Pei M, Li J, Zhang Y, et al. Expansion on a matrix deposited by nonchondrogenic urine stem cells strengthens the chondrogenic capacity of repeated-passage bone marrow stromal cells. Cell Tissue Res, 2014, 356(2): 391-403.
23. Kang HS, Choi SH, Kim BS, et al. Advanced properties of urine derived stem cells compared to adipose tissue derived stem cells in terms of cell proliferation, immune modulation and multi differentiation. J Korean Med Sci, 2015, 30(12): 1764-1776.
24. Shi Y, Liu G, Shantaram B, et al. 736 Urine derived stem cells with high telomerase activity for cell based therapy in urology. Journal of Urology, 2012, 187(4): e302.
25. Tian H, Bharadwaj S, Liu Y, et al. Differentiation of human bone marrow mesenchymal stem cells into bladder cells: potential for urological tissue engineering. Tissue Eng Part A, 2010, 16(5): 1769-1779.
26. Zhang Y, Lin HK, Frimberger D, et al. Growth of bone marrow stromal cells on small intestinal submucosa: an alternative cell source for tissue engineered bladder. BJU Int, 2005, 96(7): 1120-1125.
27. Guan J, Zhang J, Guo S, et al. Human urine-derived stem cells can be induced into osteogenic lineage by silicate bioceramics via activation of the Wnt/β-catenin signaling pathway. Biomaterials, 2015, 55: 1-11.
28. Guan J, Zhang J, Zhu Z, et al. Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells. Stem Cell Res Ther, 2015, 6: 5.
29. Kim SW, Jung JH, Lamsal K, et al. Antifungal effects of silver nanoparticles (AgNPs) against various plant pathogenic fungi. Mycobiology, 2012, 40(1): 53-58.
30. Qin H, Zhu C, An Z, et al. Silver nanoparticles promote osteogenic differentiation of human urine-derived stem cells at noncytotoxic concentrations. Int J Nanomedicine, 2014, 9: 2469-2478.
31. Guan J, Zhang J, Li H, et al. Human urine derived stem cells in combination with β-TCP can be applied for bone regeneration. PLoS One, 2015, 10(5): e0125253.
32. Huang BJ, Hu JC, Athanasiou KA. Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials, 2016, 98: 1-22.
33. Zhao Z, Zhou X, Guan J, et al. Co-implantation of bone marrow mesenchymal stem cells and chondrocytes increase the viability of chondrocytes in rat osteo-chondral defects. Oncol Lett, 2018, 15(5): 7021-7027.
34. Chen L, Li L, Xing F, et al. Human urine-derived stem cells: potential for cell-based therapy of cartilage defects. Stem Cells Int, 2018, 2018: 4686259.
35. Fu Y, Guan J, Guo S, et al. Human urine-derived stem cells in combination with polycaprolactone/gelatin nanofibrous membranes enhance wound healing by promoting angiogenesis. J Transl Med, 2014, 12: 274.
36. Dong X, Chang J, Li H. Bioglass promotes wound healing through modulating the paracrine effects between macrophages and repairing cells. Journal of Materials Chemistry B, 2017, 26: 5.
37. Zhang Y, Niu X, Dong X, et al. Bioglass enhanced wound healing ability of urine-derived stem cells through promoting paracrine effects between stem cells and recipient cells. J Tissue Eng Regen Med, 2018, 12(3): e1609-e1622.
38. Hu G, Drescher KM, Chen XM. Exosomal miRNAs: biological properties and therapeutic potential. Front Genet, 2012, 3: 56.
39. Chen CY, Rao SS, Ren L, et al. Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis. Theranostics, 2018, 8(6): 1607-1623.
40. Chen W, Xie M, Yang B, et al. Skeletal myogenic differentiation of human urine-derived cells as a potential source for skeletal muscle regeneration. J Tissue Eng Regen Med, 2017, 11(2): 334-341.
41. Kim EY, Page P, Dellefave-Castillo LM, et al. Direct reprogramming of urine-derived cells with inducible MyoD for modeling human muscle disease. Skelet Muscle, 2016, 6: 32.
42. Yang Q, Chen X, Zheng T, et al. Transplantation of human urine-derived stem cells transfected with pigment epithelium-derived factor to protect erectile function in a rat model of cavernous nerve injury. Cell Transplant, 2016, 25(11): 1987-2001.
43. Nakagawa M, Koyanagi M, Tanabe K, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol, 2008, 26(1): 101-106.
44. Zhao XY, Li W, Lv Z, et al. iPS cells produce viable mice through tetraploid complementation. Nature, 2009, 461(7260): 86-90.
45. Stadtfeld M, Maherali N, Breault DT, et al. Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell, 2008, 2(3): 230-240.
46. Zhang SZ, Li HF, Ma LX, et al. Urine-derived induced pluripotent stem cells as a modeling tool for paroxysmal kinesigenic dyskinesia. Biol Open, 2015, 4(12): 1744-1752.
47. Afzal MZ, Strande JL. Generation of induced pluripotent stem cells from muscular dystrophy patients: efficient integration-free reprogramming of urine derived cells. J Vis Exp, 2015, (95): 52032.
48. Wang L, Li X, Huang W, et al. TGFβ signaling regulates the choice between pluripotent and neural fates during reprogramming of human urine derived cells. Sci Rep, 2016, 6: 22484.
49. M Lee Y, Zampieri BL, Scott-McKean JJ, et al. Generation of integration-free induced pluripotent stem cells from urine-derived cells isolated from individuals with down syndrome. Stem Cells Transl Med, 2017, 6(6): 1465-1476.
50. Aboushady IM, Salem ZA, Sabry D, et al. Comparative study of the osteogenic potential of mesenchymal stem cells derived from different sources. J Clin Exp Dent, 2018, 10(1): e7-e13.
51. Fernandes M, Valente SG, Sabongi RG, et al. Bone marrow-derived mesenchymal stem cells. Neural Regen Res, 2018, 13(1): 100-104.
52. Hakki SS, Turaç G, Bozkurt SB, et al. Comparison of different sources of mesenchymal stem cells: palatal versus lipoaspirated adipose tissue. Cells Tissues Organs, 2017, 204(5-6): 228-240.
53. Amiri F, Molaei S, Bahadori M, et al. Autophagy-modulated human bone marrow-derived mesenchymal stem cells accelerate liver restoration in mouse models of acute liver failure. Iran Biomed J, 2016, 20(3): 135-144.
54. Jung J, Choi JH, Lee Y, et al. Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4-injured rat liver model via increased autophagic mechanism. Stem Cells, 2013, 31(8): 1584-1596.
55. Crisan M, Yap S, Casteilla L, et al. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 2008, 3(3): 301-313.

Chinese Journal of Reparative and Reconstructive Surgery

The application of urine derived stem cells in regeneration of musculoskeletal system

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