Preview

Вестник Российской академии медицинских наук

Расширенный поиск

Использование стволовых клеток в терапии дегенерации межпозвонкового диска

https://doi.org/10.15690/vramn729

Полный текст:

Аннотация

Статья представляет собой обзор современных литературных данных, посвященных применению стволовых клеток в терапии дегенеративных процессов межпозвонковых дисков. Чаще всего причиной развития болевого синдрома в спине является дегенеративное поражение межпозвонковых дисков. Дегенерация дисков в настоящее время представляет собой одну из основных причин утраты трудоспособности населения. Нередко многие методы лечения не позволяют получить ожидаемых результатов, так как в большинстве своем они имеют симптоматическую направленность и не влияют на патогенез процесса. Авторами изложены современные данные о молекулярно-клеточных механизмах дегенерации межпозвонковых дисков. Представлен анализ экспериментальных исследований, проводимых в мире, демонстрирующих возможности клеточной терапии дегенеративных процессов дисков на примере использования мезенхимальных, жировых, синовиальных и костномозговых стволовых клеток. Обозначены актуальные, остающиеся нерешенными вопросы, что обусловливает необходимость проведения дальнейших экспериментальных и клинических исследований при лечении данной патологии.

Об авторах

В. А. Бывальцев
Иркутский государственный медицинский университет; Дорожная клиническая больница на ст. Иркутск-Пассажирский; Иркутский научный центр хирургии и травматологии; Иркутская государственная академия последипломного образования
Россия

доктор медицинских наук, главный нейрохирург Департамента здравоохранения ОАО «РЖД», заведующий курсом нейрохирургии Иркутского государственного медицинского университета,

заведующий научно-клиническим отделом нейрохирургии и ортопедии Иркутского научного центра хирургии и травматологии,

профессор кафедры травматологии, ортопедии и нейрохирургии Иркутской государственной медицинской академии последипломного образования,

664082, Иркутск, ул. Боткина, д. 10



И. А. Степанов
Иркутский государственный медицинский университет
Россия

аспирант курса нейрохирургии,

664003, Иркутск, ул. Красного Восстания, д. 14



Л. А. Бардонова
Иркутский государственный медицинский университет
Россия

аспирантка курса нейрохирургии,

664003, Иркутск, ул. Красного Восстания, д. 14



Е. Г. Белых
Иркутский государственный медицинский университет; Иркутский научный центр хирургии и травматологии

ассистент курса нейрохирургии;

аспирант,

664082, Иркутск, ул. Боткина, д. 10



Список литературы

1. Belykh E, Giers M, Bardonova L, et al. The role of bone morphogenetic proteins 2, 7, and 14 in approaches for intervertebral disk restoration. World Neurosurg. 2015;84(4):871–873. doi: 10.1016/j.wneu.2015.08.011.

2. Katz JN. Lumbar disc disorders and low-back pain: socioeconomic factors and consequences. J Bone Joint Surg Am. 2006;88 Suppl 2:21–24. doi: 10.2106/JBJS.E.01273.

3. Freemont AJ. The cellular pathobiology of the degenerate intervertebral disc and discogenic back pain. Rheumatology (Oxford). 2009;48(1):5–10. doi: 10.1093/rheumatology/ken396.

4. Andersson GB. Epidemiological features of chronic low-back pain. Lancet. 1999;354(9178):581–585. doi: 10.1016/S0140- 6736(99)01312-4.

5. Бывальцев В.А., Степанов И.А., Калинин А.А., Шашков К.В. Диффузионно-взвешенная магнитно-резонансная томография в диагностике дегенерации межпозвонкового диска // Меди- цинская техника. — 2016. — №4. — С. 29–32. [Byvaltsev VA, Stepanov IA, Kalinin AA, Shashkov et al. Diffuzionno-vzveshennaya magnitno-rezonansnaya tomografiya v diagnostike degeneratsii mezhpozvonkovogo diska. Med Tekh. 2016;(4):29–32. (In Russ).]

6. Vadala G, Russo F, Ambrosio L, Loppini M, Denaro V. Stem cells sources for intervertebral disc regeneration. World J Stem Cells. 2016;8(5):185−201. doi: 10.4252/wjsc.v8.i5.185.

7. Pezowicz CA, Robertson PA, Broom ND. The structural basis of interlamellar cohesion in the intervertebral disc wall. J Anat. 2006;208(3):317–330. doi: 10.1111/j.1469-7580.2006.00536.x.

8. Urban JP, McMullin JF. Swelling pressure of the inervertebral disc: influence of proteoglycan and collagen contents. Biorheology. 1985;22(2):145–157.

9. Trout JJ, Buckwalter JA, Moore KC, Landas SK. Ultrastructure of the human intervertebral disc. I. Changes in notochordal cells with age. Tissue Cell. 1982;14(2):359–369. doi: 10.1016/0040- 8166(82)90033-7.

10. Humzah MD, Soames RW. Human intervertebral disc: structure and function. Anat Rec. 1988;220(4):337–356. doi: 10.1002/ ar.1092200402.

11. Best BA, Guilak F, Setton LA, et al. Compressive mechanical properties of the human anulus fibrosus and their relationship to biochemical composition. Spine (Phila Pa 1976). 1994;19(2):212–221. doi: 10.1097/00007632-199401001-00017.

12. Boni M, Denaro V. Anatomo-clinical correlations in cervical spondylosis. In: Kehr P, Weidner A, editors. Cervical Spine I. Vienna: Springer-Verlag Wien; 1987. p. 3–20. doi: 10.1007/978-3-7091- 8882-8_1.

13. Di Martino A, Vaccaro AR, Lee JY, et al. Nucleus pulposus replacement: basic science and indications for clinical use. Spine (Phila Pa 1976). 2005;30(16 Suppl):S16–22. doi: 10.1097/01. brs.0000174530.88585.32.

14. Haefeli M, Kalberer F, Saegesser D, et al. The course of macroscopic degeneration in the human lumbar intervertebral disc. Spine (Phila Pa 1976). 2006;31(14):1522–1531. doi: 10.1097/01. brs.0000222032.52336.8e.

15. Battie MC, Videman T. Lumbar disc degeneration: epidemiology and genetics. J Bone Joint Surg Am. 2006;88 Suppl 2:3–9. doi: 10.2106/JBJS.E.01313.

16. Horner HA, Urban JP. 2001 Volvo Award Winner in Basic Science Studies: Effect of nutrient supply on the viability of cells from the nucleus pulposus of the intervertebral disc. Spine (Phila Pa 1976). 2001;26(23):2543–2549. doi: 10.1097/00007632- 200112010-00006.

17. Buckwalter JA. Aging and degeneration of the human intervertebral disc. Spine (Phila Pa 1976). 1995;20(11):1307–1314. doi: 10.1097/00007632-199506000-00022.

18. Gruber HE, Norton HJ, Hanley EN, Jr. Anti-apoptotic effects of IGF-1 and PDGF on human intervertebral disc cells in vitro. Spine (Phila Pa 1976). 2000;25(17):2153–2157. doi: 10.1097/00007632- 200009010-00002.

19. Kim DJ, Moon SH, Kim H, et al. Bone morphogenetic protein-2 facilitates expression of chondrogenic, not osteogenic, phenotype of human intervertebral disc cells. Spine (Phila Pa 1976). 2003;28(24):2679–2684. doi: 10.1097/01. BRS.0000101445.46487.16.

20. Antoniou J, Steffen T, Nelson F, et al. The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration. J Clin Invest. 1996;98(4):996–1003. doi: 10.1172/ JCI118884.

21. Gruber HE, Hanley EN, Jr. Analysis of aging and degeneration of the human intervertebral disc. Comparison of surgical specimens with normal controls. Spine (Phila Pa 1976). 1998;23(7):751–757. doi: 10.1097/00007632-199804010-00001.

22. Butler D, Trafimow JH, Andersson GB, et al. Discs degenerate before facets. Spine (Phila Pa 1976). 1990;15(2):111–113. doi: 10.1097/00007632-199002000-00012.

23. Acaroglu ER, Latridis JC, Setton LA, et al. Degeneration and aging affect the tensile behavior of human lumbar anulus fibrosus. Spine (Phila Pa 1976). 1995;20(24):2690–2701. doi: 10.1097/00007632- 199512150-00010.

24. Vernon-Roberts B. The biology of the intervertebral disc. Boca Raton, FL: CRC Press; 1988.

25. Urban JP, Smith S, Fairbank JC. Nutrition of the intervertebral disc. Spine (Phila Pa 1976). 2004;29(23):2700–2709. doi: 10.1097/01.brs.0000146499.97948.52.

26. Masuda K, Oegema TR, Jr., An HS. Growth factors and treatment of intervertebral disc degeneration. Spine (Phila Pa 1976). 2004;29(23):2757–2769. doi: 10.1097/01.brs.0000146048.14946.af.

27. Vadala G, Sowa GA, Kang JD. Gene therapy for disc degeneration. Expert Opin Biol Ther. 2007;7(2):185–196. doi: 10.1517/14712598.7.2.185.

28. Thompson JP, Oegema TR, Jr., Bradford DS. Stimulation of mature canine intervertebral disc by growth factors. Spine (Phila Pa 1976). 1991;16(3):253–260. doi: 10.1097/00007632- 199103000-00001.

29. Li J, Yoon ST, Hutton WC. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech. 2004;17(5):423– 428. doi: 10.1097/01.bsd.0000112084.85112.5d.

30. An HS, Takegami K, Kamada H, et al. Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits. Spine (Phila Pa 1976). 2005;30(1):25–31. doi: 10.1097/01. brs.0000148002.68656.4d.

31. Nishida K, Kang JD, Gilbertson LG, et al. Modulation of the biologic activity of the rabbit intervertebral disc by gene therapy: an in vivo study of adenovirus-mediated transfer of the human transforming growth factor beta 1 encoding gene. Spine (Phila Pa 1976). 1999;24(23):2419–2425. doi: 10.1097/00007632-199912010-00002.

32. Paul R, Haydon RC, Cheng H, et al. Potential use of Sox9 gene therapy for intervertebral degenerative disc disease. Spine (Phila Pa 1976). 2003;28:755–763. doi: 10.1097/01.BRS.0000058946.64222.92.

33. Wallach CJ, Sobajima S, Watanabe Y, et al. Gene transfer of the catabolic inhibitor TIMP-1 increases measured proteoglycans in cells from degenerated human intervertebral discs. Spine (Phila Pa 1976). 2003;28(20):2331–2337. doi: 10.1097/01. BRS.0000085303.67942.94.

34. Yoon ST, Park JS, Kim KS, et al. ISSLS prize winner: LMP-1 upregulates intervertebral disc cell production of proteoglycans and BMPs in vitro and in vivo. Spine (Phila Pa 1976). 2004;29(23):2603–2611. doi: 10.1097/01.brs.0000146103.94600.85.

35. Wallach CJ, Kim JS, Sobajima S, et al. Safety assessment of intradiscal gene transfer: a pilot study. Spine J. 2006;6(2):107–112. doi: 10.1016/j.spinee.2005.05.002.

36. Vadalà G, Sowa GA, Smith L, et al. Regulation of transgene expression using an inducible system for improved safety of intervertebral disc gene therapy. Spine (Phila Pa 1976). 2007;32(13):1381–1387. doi: 10.1097/BRS.0b013e3180601215.

37. Ganey T, Libera J, Moos V, et al. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine (Phila Pa 1976). 2003;28(23):2609–2620. doi: 10.1097/01.BRS.0000097891.63063.78.

38. Nishimura K, Mochida J. Percutaneous reinsertion of the nucleus pulposus. An experimental study. Spine (Phila Pa 1976). 1998;23(14):1531–1538. doi: 10.1097/00007632-199807150-00006.

39. Sato M, Asazuma T, Ishihara M, et al. An experimental study of the regeneration of the intervertebral disc with an allograft of cultured annulus fibrosus cells using a tissue-engineering method. Spine (Phila Pa 1976). 2003;28(6):548–553. doi: 10.1097/01. BRS.0000049909.09102.60.

40. Gorensek M, Jaksimovic C, Kregar-Velikonja N, et al. Nucleus pulposus repair with cultured autologous elastic cartilage derived chondrocytes. Cell Mol Biol Lett. 2004;9(2):363–373.

41. Li X, Lee JP, Balian G, Anderson DG. Modulation of chondrocytic properties of fat-derived mesenchymal cells in co-cultures with nucleus pulposus. Connect Tissue Res. 2005;46(2):75–82. doi: 10.1080/03008200590954104.

42. Sakai D, Mochida J, Yamamoto Y, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials. 2003;24(20):3531–3541. doi: 10.1016/s0142- 9612(03)00222-9.

43. Vadalà G, Sobajima S, Lee JY, et al. In vitro interaction between muscle-derived stem cells and nucleus pulposus cells. Spine J. 2008;8(5):804–809. doi: 10.1016/j.spinee.2007.07.394.

44. Meisel HJ, Ganey T, Hutton WC, et al. Clinical experience in cellbased therapeutics: intervention and outcome. Eur Spine J. 2006;15 Suppl 3:S397–405. doi: 10.1007/s00586-006-0169-x.

45. Meisel HJ, Siodla V, Ganey T, et al. Clinical experience in cell-based therapeutics: disc chondrocyte transplantation A treatment for degenerated or damaged intervertebral disc. Biomol Eng. 2007;24(1):5–21. doi: 10.1016/j.bioeng.2006.07.002.

46. Maldonado BA, Oegema TR, Jr. Initial characterization of the metabolism of intervertebral disc cells encapsulated in microspheres. J Orthop Res. 1992;10(5):677–690. doi: 10.1002/jor.1100100510.

47. Blau HM, Brazelton TR, Weimann JM. The evolving concept of a stem cell: entity or function? Cell. 2001;105(7):829–841. doi: 10.1016/s0092-8674(01)00409-3.

48. Wobus AM. Potential of embryonic stem cells. Mol Aspects Med. 2001;22(3):149–164. doi: 10.1016/s0098-2997(01)00006-1.

49. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143– 147. doi: 10.1126/science.284.5411.143.

50. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–228. doi: 10.1089/107632701300062859.

51. Nakahara H, Goldberg VM, Caplan AI. Culture-expanded human periosteal-derived cells exhibit osteochondral potential in vivo. J Orthop Res. 1991;9(4):465–476. doi: 10.1002/jor.1100090402.

52. De Bari C, Dell’Accio F, Luyten FP. Human periosteum-derived cells maintain phenotypic stability and chondrogenic potential throughout expansion regardless of donor age. Arthritis Rheum. 2001;44(1):85-95. doi: 10.1002/1529-0131(200101)44:1<85::AIDANR12>3.0.CO;2-6.

53. De Bari C, Dell’Accio F, Tylzanowski P, Luyten FP. Multipotent mesenchymal stem cells from adult human synovial membrane. Arthritis Rheum. 2001;44(8):1928-1942. doi: 10.1002/1529-0131(200108)44:8<1928::AID-ART331>3.0.CO;2-P.

54. Lee JY, Qu-Petersen Z, Cao B, et al. Clonal isolation of muscle-derived cells capable of enhancing muscle regeneration and bone healing. J Cell Biol. 2000;150(5):1085–1100. doi: 10.1083/ jcb.150.5.1085.

55. Toma JG, Akhavan M, Fernandes KJ, et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nat Cell Biol. 2001;3(9):778–784. doi: 10.1038/ncb0901-778.

56. Brighton CT, Lorich DG, Kupcha R, et al. The pericyte as a possible osteoblast progenitor cell. Clin Orthop Relat Res. 1992;(275):287−299. doi: 10.1097/00003086-199202000-00043.

57. Reilly TM, Seldes R, Luchetti W, Brighton CT. Similarities in the phenotypic expression of pericytes and bone cells. Clin Orthop Relat Res. 1998:(346);95–103. doi: 10.1097/00003086-199801000-00014.

58. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res. 2000;2(6):477–488. doi: 10.1186/ar130.

59. Noth U, Osyczka AM, Tuli R, et al. Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res. 2002;20(5):1060–1069. doi: 10.1016/S0736- 0266(02)00018-9.

60. Osyczka AM, Noth U, Danielson KG, Tuan RS. Different osteochondral potential of clonal cell lines derived from adult human trabecular bone. Ann N Y Acad Sci. 2002;961(1):73–77. doi: 10.1111/j.1749-6632.2002.tb03054.x.

61. Risbud MV, Albert TJ, Guttapalli A, et al. Differentiation of mesenchymal stem cells towards a nucleus pulposus-like phenotype in vitro: implications for cell-based transplantation therapy. Spine (Phila Pa 1976). 2004;29(23):2627–2632. doi: 10.1097/01. brs.0000146462.92171.7f.

62. Sobajima S, Vadala G, Shimer A, et al. Feasibility of a stem cell therapy for intervertebral disc degeneration. Spine J. 2008;8(6):888– 896. doi: 10.1016/j.spinee.2007.09.011.

63. Kuroda R, Usas A, Kubo S, et al. Cartilage repair using bone morphogenetic protein 4 and muscle-derived stem cells. Arthritis Rheum. 2006;54(2):433–442. doi: 10.1002/art.21632.

64. Sacchetti B, Funari A, Michienzi S, et al. Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment. Cell. 2007;131(2):324–336. doi: 10.1016/j. cell.2007.08.025.

65. 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. doi: 10.1016/j.stem.2008.07.003.

66. Caplan AI. All MSCs are pericytes? Cell Stem Cell. 2008;3(3):229– 230. doi: 10.1016/j.stem.2008.08.008.

67. Hubert MG, Vadala G, Sowa G, et al. Gene therapy for the treatment of degenerative disk disease. J Am Acad Orthop Surg. 2008;16(6):312–319. doi: 10.5435/00124635-200806000-00003.

68. Risbud MV, Guttapalli A, Tsai TT, et al. Evidence for skeletal progenitor cells in the degenerate human intervertebral disc. Spine (Phila Pa 1976). 2007;32(23):2537–2544. doi: 10.1097/ BRS.0b013e318158dea6.

69. Blanco JF, Graciani IF, Sanchez-Guijo FM, et al. Isolation and characterization of mesenchymal stromal cells from human degenerated nucleus pulposus: comparison with bone marrow mesenchymal stromal cells from the same subjects. Spine (Phila Pa 1976). 2010;35(26):2259–2265. doi: 10.1097/ BRS.0b013e3181cb8828.

70. Steck E, Fischer J, Lorenz H, et al. Mesenchymal stem cell differentiation in an experimental cartilage defect: restriction of hypertrophy to bone-close neocartilage. Stem Cells Dev. 2009;18(7):969–978. doi: 10.1089/scd.2008.0213.

71. Le Visage C, Kim SW, Tateno K, et al. Interaction of human mesenchymal stem cells with disc cells: changes in extracellular matrix biosynthesis. Spine (Phila Pa 1976). 2006;31(18):2036–2042. doi: 10.1097/01.brs.0000231442.05245.87.

72. Hofstetter CP, Schwarz EJ, Hess D, et al. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci U S A. 2002;99(4):2199–2204. doi: 10.1073/ pnas.042678299.

73. Richardson SM, Walker RV, Parker S, et al. Intervertebral disc cell-mediated mesenchymal stem cell differentiation. Stem Cells. 2006;24(3):707–716. doi: 10.1634/stemcells.2005-0205.

74. Maroudas A, Stockwell RA, Nachemson A, Urban J. Factors involved in the nutrition of the human lumbar intervertebral disc: cellularity and diffusion of glucose in vitro. J Anat. 1975;120(Pt 1):113–130.

75. Vadala G, Studer RK, Sowa G, et al. Coculture of bone marrow mesenchymal stem cells and nucleus pulposus cells modulate gene expression profile without cell fusion. Spine (Phila Pa 1976). 2008;33(8):870–876. doi: 10.1097/BRS.0b013e31816b4619.

76. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem. 2006;98(5):1076–1084. doi: 10.1002/jcb.20886.

77. Strassburg S, Richardson SM, Freemont AJ, Hoyland JA. Coculture induces mesenchymal stem cell differentiation and modulation of the degenerate human nucleus pulposus cell phenotype. Regen Med. 2010;5(5):701–711. doi: 10.2217/rme.10.59.

78. Orozco L, Soler R, Morera C, et al. Intervertebral disc repair by autologous mesenchymal bone marrow cells: a pilot study. Transplantation. 2011;92(7):822–828. doi: 10.1097/TP.0b013e3182298a15.

79. Yoshikawa T, Ueda Y, Miyazaki K, et al. Disc regeneration therapy using marrow mesenchymal cell transplantation: a report of two case studies. Spine (Phila Pa 1976). 2010;35(11):475–480. doi: 10.1097/BRS.0b013e3181cd2cf4.

80. Lu ZF, Doulabi BZ, Wuisman PI, et al. Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells. J Cell Mol Med. 2008;12(6B):2812– 2822. doi: 10.1111/j.1582-4934.2008.00278.x.

81. Xeng TX, Doulabi BZ, Wuisman PI, Bank RA, Helder MN. Influence of collagen type II and nucleus pulposus cells on aggregation and differentiation of adipose tissue-derived stem cells. J Cell Mol Med. 2008;12:2812–2822. doi: 10.1111/ j.1582- 4934.2008.00278.x.

82. Jeong JH, Lee JH, Jin ES, et al. Regeneration of intervertebral discs in a rat disc degeneration model by implanted adipose-tissuederived stromal cells. Acta Neurochir (Wien). 2010;152(10):1771– 1777. doi: 10.1007/s00701-010-0698-2.

83. Ganey T, Hutton WC, Moseley T, et al. Intervertebral disc repair using adipose tissue-derived stem and regenerative cells: experiments in a canine model. Spine (Phila Pa 1976). 2009;34(21):2297–2304. doi: 10.1097/ BRS.0b013e3181a54157.

84. Sun Z, Luo B, Liu ZH, et al. Adipose-derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy. Int J Biol Sci. 2015;11(2):133–143. doi: 10.7150/ijbs.10598.

85. Nimura A, Muneta T, Koga H, et al. Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum. 2008;58(2):501–510. doi: 10.1002/art.23219.

86. Koga H, Muneta T, Nagase T, et al. Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res. 2008;333(2):207–215. doi: 10.1007/s00441-008-0633-5.

87. Miyamoto T, Muneta T, Tabuchi T, et al. Intradiscal transplantation of synovial mesenchymal stem cells prevents intervertebral disc degeneration through suppression of matrix metalloproteinaserelated genes in nucleus pulposus cells in rabbits. Arthritis Res Ther. 2010;12(6):R206. doi: 10.1186/ar3182.

88. Wei A, Tao H, Chung SA, et al. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs. J Orthop Res. 2009;27(3):374–379. doi: 10.1002/jor.20567.

89. Haufe SM, Mork AR. Intradiscal injection of hematopoietic stem cells in an attempt to rejuvenate the intervertebral discs. Stem Cells Dev. 2006;15(1):136–137. doi: 10.1089/scd.2006.15.136.


Для цитирования:


Бывальцев В.А., Степанов И.А., Бардонова Л.А., Белых Е.Г. Использование стволовых клеток в терапии дегенерации межпозвонкового диска. Вестник Российской академии медицинских наук. 2016;71(5):359-366. https://doi.org/10.15690/vramn729

For citation:


Byvaltsev V.A., Stepanov I.A., Bardonova L.A., Belykh E.G. The Use of Stem Cells in the Treatment of Intervertebral Disc Degeneration. Annals of the Russian academy of medical sciences. 2016;71(5):359-366. (In Russ.) https://doi.org/10.15690/vramn729

Просмотров: 197


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 0869-6047 (Print)
ISSN 2414-3545 (Online)