干细胞移植治疗脊髓损伤的研究现状_West China Medical Journal

Authors：

 汪雷 ,  宋跃明

四川大学华西医院骨科（成都 610041）;

Corresponding author：

宋跃明, Email: sym_cd@yahoo.com.cn

Keywords：

干细胞; 移植; 脊髓损伤

DOI：

10.7507/1002-0179.20150392

Video：

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Abstract Full text Figures/Tables Video References Cited by

脊髓损伤是目前脊柱外科临床上一种常见的疾病，至今仍是一个治疗难题。目前临床上的治疗手段如药物治疗、手术治疗等的治疗效果均极为有限，大部分患者经常规治疗后并未获得神经功能的实质性进展。干细胞移植后在局部能分化为目标细胞如神经元来发挥相应的功能，是目前脊髓损伤治疗的研究热点，尽管一直尚处于实验研究阶段，但仍然取得了较大的进展，为临床治疗脊髓损伤提供了较为可靠的实验依据。现根据国内外发表的相关文献综述干细胞移植治疗脊髓损伤，以期对干细胞移植的实验研究及临床治疗起到一定的参考作用。

Citation： 汪雷, 宋跃明. 干细胞移植治疗脊髓损伤的研究现状. West China Medical Journal, 2015, 30(7): 1357-1360. doi: 10.7507/1002-0179.20150392 Copy

1.	Tom VJ, Sandrow-Feinberg HR, Miller K, et al. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord[J]. J Neurosci, 2009, 29(47):14881-14890.
2.	Féron F, Perry C, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human spinal cord injury[J]. Brain, 2005, 128(Pt 12):2951-2960.
3.	Kabatas S, Teng YD. Potential roles of the neural stem cell in the restoration of the injured spinal cord:review of the literature[J].Turk Neurosurg, 2010, 20(2):103-110.
4.	Li Y, Zhang WM, Wang TH. Optimal location and time for neural stem cell transplantation into transected rat spinal cord[J]. Cell Mol Neurobiol, 2011, 31(3):407-414.
5.	Solter D. From teratocarcinomas to embryonic stem cells and beyond:a history of embryonic stem cell research[J]. Nat Rev Genet, 2006, 7(4):319-327.
6.	Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis[J]. Nature, 2004, 432(715):324-331.
7.	Mothe AJ, Kulbatski I, Parr A, et al. Adult spinal cord stem/progenitor cells transplanted as neurospheres preferentially differentiate into oligodendrocytes in the adult rat spinal cord[J]. Cell Transplant, 2008, 17(7):735-751.
8.	Dasari VR, Spomar DG, Li L, et al. Umbilical cord blood stem cell mediated downregulation of fas improves functional recovery of rats after spinal cord injury[J]. Neurochem Res, 2008, 33(1):134-149.
9.	Amoh Y, Kanoh M, Niiyama S, et al. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury:an advantageous alternative to ES and iPS cells[J]. J Cell Biochem, 2009, 107(5):1016-1020.
10.	Salewski RP, Eftekharpour E, Fehlings MG. Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury?[J]. J Cell Physiol, 2010, 222(3):515-521.
11.	Foret A, Quertainmont R, Botman O, et al. Stem cells in the adult rat spinal cord:plasticity after injury and treadmill training exercise[J]. J Neurochem, 2010, 112(3):762-772.
12.	Park HW, Lim MJ, Jung H, et al. Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury[J]. Glia, 2010, 58(9):1118-1132.
13.	Kamei N, Kwon SM, Alev C, et al. Lnk deletion reinforces the function of bone marrow progenitors in promoting neovascularization and astrogliosis following spinal cord injury[J]. Stem Cells, 2010, 28(2):365-375.
14.	Johnson PJ, Tatara A, Shiu A, et al. Controlled release of neurotrophin-3 and platelet-derived growth factor from fibrin scaffolds containing neural progenitor cells enhances survival and differentiation into neurons in a subacute model of SCI[J]. Cell Transplant, 2010, 19(1):89-101.
15.	Hsieh J, Aimone JB, Kaspar BK, et al. IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes[J]. J Cell Biol, 2004, 164(1):111-122.
16.	Veeravalli KK, Dasari VR, Tsung AJ, et al. Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury[J]. Neurobiol Dis, 2009, 36(1):200-212.
17.	Hardy SA, Maltman DJ, Przyborski SA. Mesenchymal stem cells as mediators of neural differentiation[J]. Curr Stem Cell Res Ther, 2008, 3(1):43-52.
18.	Bukovsky A, Caudle MR, Svetlikova M. Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro[J]. Cell Cycle, 2008, 7(22):3577-3583.
19.	Kim HM, Hwang DH, Lee JE, et al. Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury[J]. PLoS One, 2009, 4(3):e4987.
20.	Lee SI, Kim BG, Hwang DH, et al. Overexpression of Bcl-XL in human neural stem cells promotes graft survival and functional recovery following transplantation in spinal cord injury[J]. J Neurosci Res, 2009, 87(14):3186-3197.
21.	Shen J, Zhong XM, Duan XH, et al. Magnetic resonance imaging of mesenchymal stem cells labeled with dual (Mr and fluorescence) agents in rat spinal cord injury[J]. Acad Radiol, 2009, 16(9):1142-1154.
22.	Deda H, Inci MC, Kürekçi AE, et al. Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up[J]. Cytotherapy, 2008, 10(6):565-574.
23.	Abdelaziz OS, Marie A, Abbas M, et al. Feasibility, safety, and efficacy of directly transplanting autologous adult bone marrow stem cells in patients with chronic traumatic dorsal cord injury a pilot clinical study[J]. Neurosurg Q, 2010, 20(3):216-226.
24.	Zhang YQ, Zeng X, He LM, et al. NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro[J]. Anat Sci Int, 2010, 85(2):61-67.
25.	Wakao S, Hayashi T, Kitada M, et al. Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration[J]. Exp Neurol, 2010, 223(2):537-547.
26.	Kim K, Doi A, Wen B, et al. Epigenetic memory in induced pluripotent stem cells[J]. Nature, 2010, 467(7313):285-290.
27.	Tsuji O, Miura K, Okada Y, et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury[J]. Proc Natl Acad Sci USA, 2010, 107(28):12704-12709.
28.	Macias MY, Syring MB, Pizzi MA, et al. Pain with no gain:allodynia following neural stem cell transplantation in spinal cord injury[J]. Exp Neurol, 2006, 201(2):335-348.
29.	Hofstetter CP, Holmström NA, Lilja JA, et al. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome[J]. Nat Neurosci, 2005, 8(3):346-353.
30.	Owens J. Stem-cell treatments for spinal-cord injury may be worth the risk[J]. Nature, 2009, 458(7242):1101.
31.	Matsuda R, Yoshikawa M, Kimura H, et al. Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development[J]. Cell Transplant, 2009, 18(1):39-54.
32.	Sato Y, Oohira A. Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification[J]. Curr Stem Cell Res Ther, 2009, 4(3):200-209.
33.	Zhang YJ, Zhang W, Lin CG, et al. Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats[J]. J Neurol Sci, 2012, 313(1/2):64-74.
34.	Lu HX, Hao ZM, Jiao Q, et al. Neurotrophin-3 gene transduction of mouse neural stem cells promotes proliferation and neuronal differentiation in organotypic hippocampal slice cultures[J]. Med Sci Monit, 2011, 17(11):BR305-BR311.
35.	Hejcl A, Sedý J, Kapcalová M, et al. HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome in chronic spinal cord injury[J]. Stem Cells Dev, 2010, 19(10):1535-1546.
36.	Park J, Lim E, Back S, et al. Nerve regeneration following spinal cord injury using matrix metalloproteinase-sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor[J]. J Biomed Mater Res A, 2010, 93(3):1091-1099.
37.	Hatami M, Mehrjardi NZ, Kiani S, et al. Human embryonic stem cell-derived neural precursor transplants in collagen scaffolds promote recovery in injured rat spinal cord[J]. Cytotherapy, 2009, 11(5):618-630.

1. Tom VJ, Sandrow-Feinberg HR, Miller K, et al. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord[J]. J Neurosci, 2009, 29(47):14881-14890.
2. Féron F, Perry C, Cochrane J, et al. Autologous olfactory ensheathing cell transplantation in human spinal cord injury[J]. Brain, 2005, 128(Pt 12):2951-2960.
3. Kabatas S, Teng YD. Potential roles of the neural stem cell in the restoration of the injured spinal cord:review of the literature[J].Turk Neurosurg, 2010, 20(2):103-110.
4. Li Y, Zhang WM, Wang TH. Optimal location and time for neural stem cell transplantation into transected rat spinal cord[J]. Cell Mol Neurobiol, 2011, 31(3):407-414.
5. Solter D. From teratocarcinomas to embryonic stem cells and beyond:a history of embryonic stem cell research[J]. Nat Rev Genet, 2006, 7(4):319-327.
6. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis[J]. Nature, 2004, 432(715):324-331.
7. Mothe AJ, Kulbatski I, Parr A, et al. Adult spinal cord stem/progenitor cells transplanted as neurospheres preferentially differentiate into oligodendrocytes in the adult rat spinal cord[J]. Cell Transplant, 2008, 17(7):735-751.
8. Dasari VR, Spomar DG, Li L, et al. Umbilical cord blood stem cell mediated downregulation of fas improves functional recovery of rats after spinal cord injury[J]. Neurochem Res, 2008, 33(1):134-149.
9. Amoh Y, Kanoh M, Niiyama S, et al. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury:an advantageous alternative to ES and iPS cells[J]. J Cell Biochem, 2009, 107(5):1016-1020.
10. Salewski RP, Eftekharpour E, Fehlings MG. Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury?[J]. J Cell Physiol, 2010, 222(3):515-521.
11. Foret A, Quertainmont R, Botman O, et al. Stem cells in the adult rat spinal cord:plasticity after injury and treadmill training exercise[J]. J Neurochem, 2010, 112(3):762-772.
12. Park HW, Lim MJ, Jung H, et al. Human mesenchymal stem cell-derived Schwann cell-like cells exhibit neurotrophic effects, via distinct growth factor production, in a model of spinal cord injury[J]. Glia, 2010, 58(9):1118-1132.
13. Kamei N, Kwon SM, Alev C, et al. Lnk deletion reinforces the function of bone marrow progenitors in promoting neovascularization and astrogliosis following spinal cord injury[J]. Stem Cells, 2010, 28(2):365-375.
14. Johnson PJ, Tatara A, Shiu A, et al. Controlled release of neurotrophin-3 and platelet-derived growth factor from fibrin scaffolds containing neural progenitor cells enhances survival and differentiation into neurons in a subacute model of SCI[J]. Cell Transplant, 2010, 19(1):89-101.
15. Hsieh J, Aimone JB, Kaspar BK, et al. IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes[J]. J Cell Biol, 2004, 164(1):111-122.
16. Veeravalli KK, Dasari VR, Tsung AJ, et al. Human umbilical cord blood stem cells upregulate matrix metalloproteinase-2 in rats after spinal cord injury[J]. Neurobiol Dis, 2009, 36(1):200-212.
17. Hardy SA, Maltman DJ, Przyborski SA. Mesenchymal stem cells as mediators of neural differentiation[J]. Curr Stem Cell Res Ther, 2008, 3(1):43-52.
18. Bukovsky A, Caudle MR, Svetlikova M. Steroid-mediated differentiation of neural/neuronal cells from epithelial ovarian precursors in vitro[J]. Cell Cycle, 2008, 7(22):3577-3583.
19. Kim HM, Hwang DH, Lee JE, et al. Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury[J]. PLoS One, 2009, 4(3):e4987.
20. Lee SI, Kim BG, Hwang DH, et al. Overexpression of Bcl-XL in human neural stem cells promotes graft survival and functional recovery following transplantation in spinal cord injury[J]. J Neurosci Res, 2009, 87(14):3186-3197.
21. Shen J, Zhong XM, Duan XH, et al. Magnetic resonance imaging of mesenchymal stem cells labeled with dual (Mr and fluorescence) agents in rat spinal cord injury[J]. Acad Radiol, 2009, 16(9):1142-1154.
22. Deda H, Inci MC, Kürekçi AE, et al. Treatment of chronic spinal cord injured patients with autologous bone marrow-derived hematopoietic stem cell transplantation:1-year follow-up[J]. Cytotherapy, 2008, 10(6):565-574.
23. Abdelaziz OS, Marie A, Abbas M, et al. Feasibility, safety, and efficacy of directly transplanting autologous adult bone marrow stem cells in patients with chronic traumatic dorsal cord injury a pilot clinical study[J]. Neurosurg Q, 2010, 20(3):216-226.
24. Zhang YQ, Zeng X, He LM, et al. NT-3 gene modified Schwann cells promote TrkC gene modified mesenchymal stem cells to differentiate into neuron-like cells in vitro[J]. Anat Sci Int, 2010, 85(2):61-67.
25. Wakao S, Hayashi T, Kitada M, et al. Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration[J]. Exp Neurol, 2010, 223(2):537-547.
26. Kim K, Doi A, Wen B, et al. Epigenetic memory in induced pluripotent stem cells[J]. Nature, 2010, 467(7313):285-290.
27. Tsuji O, Miura K, Okada Y, et al. Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury[J]. Proc Natl Acad Sci USA, 2010, 107(28):12704-12709.
28. Macias MY, Syring MB, Pizzi MA, et al. Pain with no gain:allodynia following neural stem cell transplantation in spinal cord injury[J]. Exp Neurol, 2006, 201(2):335-348.
29. Hofstetter CP, Holmström NA, Lilja JA, et al. Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome[J]. Nat Neurosci, 2005, 8(3):346-353.
30. Owens J. Stem-cell treatments for spinal-cord injury may be worth the risk[J]. Nature, 2009, 458(7242):1101.
31. Matsuda R, Yoshikawa M, Kimura H, et al. Cotransplantation of mouse embryonic stem cells and bone marrow stromal cells following spinal cord injury suppresses tumor development[J]. Cell Transplant, 2009, 18(1):39-54.
32. Sato Y, Oohira A. Chondroitin sulfate, a major niche substance of neural stem cells, and cell transplantation therapy of neurodegeneration combined with niche modification[J]. Curr Stem Cell Res Ther, 2009, 4(3):200-209.
33. Zhang YJ, Zhang W, Lin CG, et al. Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats[J]. J Neurol Sci, 2012, 313(1/2):64-74.
34. Lu HX, Hao ZM, Jiao Q, et al. Neurotrophin-3 gene transduction of mouse neural stem cells promotes proliferation and neuronal differentiation in organotypic hippocampal slice cultures[J]. Med Sci Monit, 2011, 17(11):BR305-BR311.
35. Hejcl A, Sedý J, Kapcalová M, et al. HPMA-RGD hydrogels seeded with mesenchymal stem cells improve functional outcome in chronic spinal cord injury[J]. Stem Cells Dev, 2010, 19(10):1535-1546.
36. Park J, Lim E, Back S, et al. Nerve regeneration following spinal cord injury using matrix metalloproteinase-sensitive, hyaluronic acid-based biomimetic hydrogel scaffold containing brain-derived neurotrophic factor[J]. J Biomed Mater Res A, 2010, 93(3):1091-1099.
37. Hatami M, Mehrjardi NZ, Kiani S, et al. Human embryonic stem cell-derived neural precursor transplants in collagen scaffolds promote recovery in injured rat spinal cord[J]. Cytotherapy, 2009, 11(5):618-630.

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干细胞移植治疗脊髓损伤的研究现状

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