血-脊髓屏障修复在脊髓损伤治疗中作用的研究进展
|
摘要
<正>由于现代社会交通、工业的发展,脊髓损伤(spinal cord injury,SCI)的患者不断增加,我国SCI年患病率为37人/100万,尤以青壮年男性高发,但对于SCI目前尚缺乏有效的治疗手段,临床预后较差[1],其导致的瘫痪和劳动力丧失给患者、家庭和社会带来沉重的经济负担[2]。血-脊髓屏障(blood-spinal cord barrier,BSCB)是循环系统在中枢神经系统中形成的特殊结构,介导血管内外的物质交换[3]。研究表明,SCI后BSCB的破坏可导致脊髓水肿、出血、氧
引文
1.Witiw CD,Fehlings MG.Acute spinal cord injury[J].J Spinal Disord Tech,2015,28(6):202-210.
2.陈星月,陈栋,陈春慧,等.中国创伤性脊髓损伤流行病学和疾病经济负担的系统评价[J].中国循证医学杂志,2018,18(2):143-150.
3.Oudega M.Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair[J].Cell Tissue Res,2012,349(1):269-288.
4.Haggerty AE,Maldonado-Lasunción I,Oudega M.Biomaterials for revascularization and immunomodulation after spinal cord injury[J].Biomed Mater,2018,25,13(4):044105.
5.许兵,张俞.血脑屏障的研究进展[J].生理学报,2016,68(3):306-322.
6.Komarova Y,Malik AB.Regulation of endothelial permeability via paracellular and transcellular transport pathways[J].Annu Rev Physiol,2010,72:463-493.
7.Armulik A,GenovéG,Betsholtz C.Pericytes:developmental,physiological,and pathological perspectives,problems,and promises[J].Dev Cell,2011,21(2):193-215.
8.Daneman R,Prat A.The Blood-brain barrier[J].Cold Spring Harb Perspect Biol,2015,7(1):a020412.
9.Dejana E,Orsenigo F,Lampugnani MG.The role of adherens junctions and VE-cadherin in the control of vascular permeability[J].J Cell Sci,2008,121(Pt 13):2115-2122.
10.Sorokin L.The impact of the extracellular matrix on inflammation[J].Nat Rev Immunol,2010,10(10):712-723.
11.Nagaraja TN,Karki K,Ewing JR,et al.Identification of variations in blood-brain barrier opening after cerebral ischemia by dual contrast-enhanced magnetic resonance imaging and T 1sat measurements[J].Stroke,2008,39(2):427-432.
12.Shi Y,Jiang X,Zhang L,et al.Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood-brain barrier disruption after ischemic brain injury[J].Proc Natl Acad Sci U S A,2017,114(7):E1243-E1252.
13.Hawkins BT,Davis TP.The blood-brain barrier/neurovascular unit in health and disease[J].Pharmacol Rev,2005,57(2):173-185.
14.Andreone BJ,Chow BW,Tata A,et al.Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis[J].Neuron,2017,94(3):581-594.
15.Nag S,Manias JL,Stewart DJ.Expression of endothelial phosphorylated caveolin-1 is increased in brain injury[J].Neuropathol Appl Neurobiol,2009,35(4):417-426.
16.Brightman MW,Zis K,Anders J.Morphology of cerebral endothelium and astrocytes as determinants of the neuronal microenvironment[J].Acta Neuropathol Suppl,1983,8:21-33.
17.Yamamoto M,Ramirez SH,Sato S,et al.Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells[J].Am J Pathol,2008,172(2):521-533.
18.Rochfort KD,Cummins PM.The blood-brain barrier endothelium:a target for pro-inflammatory cytokines[J].Biochem Soc Trans,2015,43(4):702-706.
19.Dobrogowska DH,Lossinsky AS,Tarnawski M,et al.Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor[J].J Neurocytol,1998,27(3):163-173.
20.Wang W,Dentler WL,Borchardt RT.VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly[J].Am J Physiol Heart Circ Physiol,2001,280(1):H434-440.
21.Maisonpierre PC,Suri C,Jones PF,et al.Angiopoietin-2,a natural antagonist for Tie2 that fisrupts in vivo angiogenesis[J].Science,1997,277(5322):55-60.
22.Candelario-Jalil E,Yang Y,Rosenberg GA.Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia[J].Neuroscience,2009,158(3):983-994.
23.Noble LJ,Donovan F,Igarashi T,et al.Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events[J].J Neurosci,2002,22(17):7526-7535.
24.Fassbender JM,Whittemore SR,Hagg T.Targeting microvasculature for neuroprotection after SCI[J].Neurotherapeutics,2011,8(2):240-251.
25.Jiang X,Andjelkovic AV,Zhu L,et al.Blood-brain barrier dysfunction and recovery after ischemic stroke[J].Prog Neurobiol,2018,163-164:144-171.
26.Blight AR.Morphometric analysis of blood vessels in chronic experimental spinal cord injury:hypervascularity and recovery of function[J].J Neurol Sci,1991,106(2):158-174.
27.Widenfalk J,Lipson A,Jubran M,et al.Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury[J].Neuroscience,2003,120(4):951-960.
28.Benton RL,Whittemore SR.VEGF165 therapy exacerbates secondary damage following spinal cord injury[J].Neurochem Res,2003,28(11):1693-1703.
29.Han S,Arnold SA,Sithu SD,et al.Rescuing vasculature with intravenous angiopoietin-1 and alpha v beta 3 integrin peptide is protective after spinal cord injury[J].Brain,2010,133(Pt 4):1026-1042.
30.Kitamura K,Iwanami A,Nakamura M,et al.Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury[J].J Neurosci Res,2007,85(11):2332-2342.
31.Kang CE,Clarkson R,Tator CH,et al.Spinal cord blood flow and blood vessel permeability measured by dynamic computed tomography imaging in rats after localized delivery of fibroblast growth factor[J].J Neurotrauma,2010,27(11):2041-2053.
32.Ju R,Wen Y,Gou R,et al.The Experimental therapy on brain ischemia by improvement of local angiogenesis with tissue engineering in the mouse[J].Cell Transplant,2014,23(Suppl 1):S83-95.
33.Lutton C,Young YW,Williams R,et al.Combined VEGFand PDGF treatment reduces secondary degeneration after spinal cord injury[J].J Neurotrauma,2012,29(5):957-970.
34.Banfi A,Von DG,Gianni-Barrera R,et al.Therapeutic angiogenesis due to balanced single-vector delivery of VEGFand PDGF-BB[J].FASEB J,2012,26(6):2486-2497.
35.Kim JH,Jung Y,Kim SH,et al.The enhancement of mature vessel formation and cardiac function in infarcted hearts using dual growth factor delivery with self-assembling peptides[J].Biomaterials,2011,32(26):6080-6088.
36.Zhang J,Chopp M.Cell-based therapy for ischemic stroke[J].Expert Opin Biol Ther,2013,13(9):1229-1240.
37.Muheremu A,Peng J,Ao Q.Stem cell based therapies for spinal cord injury[J].Tissue Cell,2016,48(4):328-333.
38.Asahara T,Isner JM.Isolation of putative progenitor endothelial cells for angiogenesis[J].Science,1997,275(5302):964-967.
39.Guo X,Liu L,Zhang M,et al.Correlation of CD34+cells with tissue angiogenesis after traumatic brain injury in a rat model[J].J Neurotrauma,2009,26(8):1337-1344.
40.Greco NJ,Bhakta S,Winter DG,et al.Umbilical cord blood-selected CD133(+)cells exhibit vasculogenic functionality in vitro and in vivo[J].Cytotherapy,2010,12(1):67-78.
41.Sasaki H,Ishikawa M,Tanaka N,et al.Administration of human peripheral blood-derived CD133+cells accelerates functional recovery in a rat spinal cord injury model[J].Spine(Phila Pa 1976),2009,34(3):249-254.
42.Rosell A,Morancho A,Navarrosobrino M,et al.Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice[J].PLoS One,2013,8(9):e73244.
43.Hristov M,Weber C.Endothelial progenitor cells:characterization,pathophysiology,and possible clinical relevance[J].JCell Mol Med,2004,8(4):498-508.
44.Rafii S,Lyden D.Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J].Nat Med,2003,9(6):702-712.
45.Oswald J1,Boxberger S,J覬rgensen B,et al.Mesenchymal stem cells can be differentiated into endothelial cells in vitro[J].Stem Cells,2004,22(3):377-384.
46.Ritfeld GJ,Nandoe Tewarie RD,Vajn K,et al.Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats[J].Cell Transplant,2012,21(7):1561-1575.
47.Nandoe Tewarie RD,Bossers K,Ritfeld GJ,et al.Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair[J].Restor Neurol Neurosci,2011,29(3):187-201.
48.Slaughter BV,Khurshid SS,Fisher OZ,et al.Hydrogels in regenerative medicine[J].Adv Mater,2009,21(32-33):3307-3329.
49.Martino MM,Brkic S,Bovo E,et al.Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine[J].Front Bioeng Biotechnol,2015,3:45.
50.Vempati P,Popel AS,Mac Gabhann F.Formation of VEGFisoform-specific spatial distributions governing angiogenesis:computational analysis[J].BMC Syst Biol,2011,5:59.
51.Briquez PS,Clegg LE,Martino MM,et al.Design principles for therapeutic angiogenic materials[J].J Biomater Appl,2011,26(4):383-417.
52.Devolder R,Kong HJ.Hydrogels for in vivo-like three-dimensional cellular studies[J].Wiley Interdiscip Rev Syst Biol Med,2012,4(4):351-365.
53.Liekens S,De CE,Neyts J.Angiogenesis:regulators and clinical applications[J].Biochem Pharmacol,2001,61(3):253-270.
54.张驰,高明勇,全大萍.脊髓损伤修复再生支架材料研究进展[J].高分子通报,2016,(5):52-67.
55.Rauch MF,Hynes SR,Bertram J,et al.Engineering angiogenesis following spinal cord injury:a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier[J].Eur J Neurosci,2009,29(1):132-145.
56.Arulmoli J,Wright HJ,Phan DTT,et al.Combination scaffolds of salmon fibrin,hyaluronic acid,and laminin for human neural stem cell and vascular tissue engineering[J].Acta Biomater,2016,43:122-138.
57.Xue L,Greisler HP.Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based3-dimensional angiogenesis system[J].Surgery,2002,132(2):259-267.
58.Kroon ME,van Schie ML,Van d VB,et al.Collagen type 1retards tube formation by human microvascular endothelial cells in a fibrin matrix[J].Angiogenesis,2002,5(4):257-265.
59.Wang L,Shi Q,Dai J,et al.Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold[J].J Orthop Res,2017,36(3):1024-1034.
60.Hong LTA,Kim YM,Park HH,et al.An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling[J].Nat Commun,2017,8(1):533.
61.Zeng CG,Xiong Y,Xie G,et al.Fabrication and evaluation of PLLA multichannel conduits with nanofibrous microstructure for the differentiation of NSCs in vitro[J].Tissue Eng Part A,2014,20(5-6):1038-1048.
62.Duan H,Ge W,Zhang A,et al.Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury[J].Proc Natl Acad Sci U S A,2015,112(43):13360-13365.
63.Zeng X,Zeng YS,Ma YH,et al.Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation,promote angiogenesis,and reduce cavity formation in experimental spinal cord injury[J].Cell Transplant,2011,20(11-12):1881-1899.
64.Shafiee A,Atala A.Printing technologies for medical applications[J].Trends Mol Med,2016,22(3):254-265.
2.陈星月,陈栋,陈春慧,等.中国创伤性脊髓损伤流行病学和疾病经济负担的系统评价[J].中国循证医学杂志,2018,18(2):143-150.
3.Oudega M.Molecular and cellular mechanisms underlying the role of blood vessels in spinal cord injury and repair[J].Cell Tissue Res,2012,349(1):269-288.
4.Haggerty AE,Maldonado-Lasunción I,Oudega M.Biomaterials for revascularization and immunomodulation after spinal cord injury[J].Biomed Mater,2018,25,13(4):044105.
5.许兵,张俞.血脑屏障的研究进展[J].生理学报,2016,68(3):306-322.
6.Komarova Y,Malik AB.Regulation of endothelial permeability via paracellular and transcellular transport pathways[J].Annu Rev Physiol,2010,72:463-493.
7.Armulik A,GenovéG,Betsholtz C.Pericytes:developmental,physiological,and pathological perspectives,problems,and promises[J].Dev Cell,2011,21(2):193-215.
8.Daneman R,Prat A.The Blood-brain barrier[J].Cold Spring Harb Perspect Biol,2015,7(1):a020412.
9.Dejana E,Orsenigo F,Lampugnani MG.The role of adherens junctions and VE-cadherin in the control of vascular permeability[J].J Cell Sci,2008,121(Pt 13):2115-2122.
10.Sorokin L.The impact of the extracellular matrix on inflammation[J].Nat Rev Immunol,2010,10(10):712-723.
11.Nagaraja TN,Karki K,Ewing JR,et al.Identification of variations in blood-brain barrier opening after cerebral ischemia by dual contrast-enhanced magnetic resonance imaging and T 1sat measurements[J].Stroke,2008,39(2):427-432.
12.Shi Y,Jiang X,Zhang L,et al.Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood-brain barrier disruption after ischemic brain injury[J].Proc Natl Acad Sci U S A,2017,114(7):E1243-E1252.
13.Hawkins BT,Davis TP.The blood-brain barrier/neurovascular unit in health and disease[J].Pharmacol Rev,2005,57(2):173-185.
14.Andreone BJ,Chow BW,Tata A,et al.Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis[J].Neuron,2017,94(3):581-594.
15.Nag S,Manias JL,Stewart DJ.Expression of endothelial phosphorylated caveolin-1 is increased in brain injury[J].Neuropathol Appl Neurobiol,2009,35(4):417-426.
16.Brightman MW,Zis K,Anders J.Morphology of cerebral endothelium and astrocytes as determinants of the neuronal microenvironment[J].Acta Neuropathol Suppl,1983,8:21-33.
17.Yamamoto M,Ramirez SH,Sato S,et al.Phosphorylation of claudin-5 and occludin by rho kinase in brain endothelial cells[J].Am J Pathol,2008,172(2):521-533.
18.Rochfort KD,Cummins PM.The blood-brain barrier endothelium:a target for pro-inflammatory cytokines[J].Biochem Soc Trans,2015,43(4):702-706.
19.Dobrogowska DH,Lossinsky AS,Tarnawski M,et al.Increased blood-brain barrier permeability and endothelial abnormalities induced by vascular endothelial growth factor[J].J Neurocytol,1998,27(3):163-173.
20.Wang W,Dentler WL,Borchardt RT.VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly[J].Am J Physiol Heart Circ Physiol,2001,280(1):H434-440.
21.Maisonpierre PC,Suri C,Jones PF,et al.Angiopoietin-2,a natural antagonist for Tie2 that fisrupts in vivo angiogenesis[J].Science,1997,277(5322):55-60.
22.Candelario-Jalil E,Yang Y,Rosenberg GA.Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia[J].Neuroscience,2009,158(3):983-994.
23.Noble LJ,Donovan F,Igarashi T,et al.Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events[J].J Neurosci,2002,22(17):7526-7535.
24.Fassbender JM,Whittemore SR,Hagg T.Targeting microvasculature for neuroprotection after SCI[J].Neurotherapeutics,2011,8(2):240-251.
25.Jiang X,Andjelkovic AV,Zhu L,et al.Blood-brain barrier dysfunction and recovery after ischemic stroke[J].Prog Neurobiol,2018,163-164:144-171.
26.Blight AR.Morphometric analysis of blood vessels in chronic experimental spinal cord injury:hypervascularity and recovery of function[J].J Neurol Sci,1991,106(2):158-174.
27.Widenfalk J,Lipson A,Jubran M,et al.Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury[J].Neuroscience,2003,120(4):951-960.
28.Benton RL,Whittemore SR.VEGF165 therapy exacerbates secondary damage following spinal cord injury[J].Neurochem Res,2003,28(11):1693-1703.
29.Han S,Arnold SA,Sithu SD,et al.Rescuing vasculature with intravenous angiopoietin-1 and alpha v beta 3 integrin peptide is protective after spinal cord injury[J].Brain,2010,133(Pt 4):1026-1042.
30.Kitamura K,Iwanami A,Nakamura M,et al.Hepatocyte growth factor promotes endogenous repair and functional recovery after spinal cord injury[J].J Neurosci Res,2007,85(11):2332-2342.
31.Kang CE,Clarkson R,Tator CH,et al.Spinal cord blood flow and blood vessel permeability measured by dynamic computed tomography imaging in rats after localized delivery of fibroblast growth factor[J].J Neurotrauma,2010,27(11):2041-2053.
32.Ju R,Wen Y,Gou R,et al.The Experimental therapy on brain ischemia by improvement of local angiogenesis with tissue engineering in the mouse[J].Cell Transplant,2014,23(Suppl 1):S83-95.
33.Lutton C,Young YW,Williams R,et al.Combined VEGFand PDGF treatment reduces secondary degeneration after spinal cord injury[J].J Neurotrauma,2012,29(5):957-970.
34.Banfi A,Von DG,Gianni-Barrera R,et al.Therapeutic angiogenesis due to balanced single-vector delivery of VEGFand PDGF-BB[J].FASEB J,2012,26(6):2486-2497.
35.Kim JH,Jung Y,Kim SH,et al.The enhancement of mature vessel formation and cardiac function in infarcted hearts using dual growth factor delivery with self-assembling peptides[J].Biomaterials,2011,32(26):6080-6088.
36.Zhang J,Chopp M.Cell-based therapy for ischemic stroke[J].Expert Opin Biol Ther,2013,13(9):1229-1240.
37.Muheremu A,Peng J,Ao Q.Stem cell based therapies for spinal cord injury[J].Tissue Cell,2016,48(4):328-333.
38.Asahara T,Isner JM.Isolation of putative progenitor endothelial cells for angiogenesis[J].Science,1997,275(5302):964-967.
39.Guo X,Liu L,Zhang M,et al.Correlation of CD34+cells with tissue angiogenesis after traumatic brain injury in a rat model[J].J Neurotrauma,2009,26(8):1337-1344.
40.Greco NJ,Bhakta S,Winter DG,et al.Umbilical cord blood-selected CD133(+)cells exhibit vasculogenic functionality in vitro and in vivo[J].Cytotherapy,2010,12(1):67-78.
41.Sasaki H,Ishikawa M,Tanaka N,et al.Administration of human peripheral blood-derived CD133+cells accelerates functional recovery in a rat spinal cord injury model[J].Spine(Phila Pa 1976),2009,34(3):249-254.
42.Rosell A,Morancho A,Navarrosobrino M,et al.Factors secreted by endothelial progenitor cells enhance neurorepair responses after cerebral ischemia in mice[J].PLoS One,2013,8(9):e73244.
43.Hristov M,Weber C.Endothelial progenitor cells:characterization,pathophysiology,and possible clinical relevance[J].JCell Mol Med,2004,8(4):498-508.
44.Rafii S,Lyden D.Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration[J].Nat Med,2003,9(6):702-712.
45.Oswald J1,Boxberger S,J覬rgensen B,et al.Mesenchymal stem cells can be differentiated into endothelial cells in vitro[J].Stem Cells,2004,22(3):377-384.
46.Ritfeld GJ,Nandoe Tewarie RD,Vajn K,et al.Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats[J].Cell Transplant,2012,21(7):1561-1575.
47.Nandoe Tewarie RD,Bossers K,Ritfeld GJ,et al.Early passage bone marrow stromal cells express genes involved in nervous system development supporting their relevance for neural repair[J].Restor Neurol Neurosci,2011,29(3):187-201.
48.Slaughter BV,Khurshid SS,Fisher OZ,et al.Hydrogels in regenerative medicine[J].Adv Mater,2009,21(32-33):3307-3329.
49.Martino MM,Brkic S,Bovo E,et al.Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine[J].Front Bioeng Biotechnol,2015,3:45.
50.Vempati P,Popel AS,Mac Gabhann F.Formation of VEGFisoform-specific spatial distributions governing angiogenesis:computational analysis[J].BMC Syst Biol,2011,5:59.
51.Briquez PS,Clegg LE,Martino MM,et al.Design principles for therapeutic angiogenic materials[J].J Biomater Appl,2011,26(4):383-417.
52.Devolder R,Kong HJ.Hydrogels for in vivo-like three-dimensional cellular studies[J].Wiley Interdiscip Rev Syst Biol Med,2012,4(4):351-365.
53.Liekens S,De CE,Neyts J.Angiogenesis:regulators and clinical applications[J].Biochem Pharmacol,2001,61(3):253-270.
54.张驰,高明勇,全大萍.脊髓损伤修复再生支架材料研究进展[J].高分子通报,2016,(5):52-67.
55.Rauch MF,Hynes SR,Bertram J,et al.Engineering angiogenesis following spinal cord injury:a coculture of neural progenitor and endothelial cells in a degradable polymer implant leads to an increase in vessel density and formation of the blood-spinal cord barrier[J].Eur J Neurosci,2009,29(1):132-145.
56.Arulmoli J,Wright HJ,Phan DTT,et al.Combination scaffolds of salmon fibrin,hyaluronic acid,and laminin for human neural stem cell and vascular tissue engineering[J].Acta Biomater,2016,43:122-138.
57.Xue L,Greisler HP.Angiogenic effect of fibroblast growth factor-1 and vascular endothelial growth factor and their synergism in a novel in vitro quantitative fibrin-based3-dimensional angiogenesis system[J].Surgery,2002,132(2):259-267.
58.Kroon ME,van Schie ML,Van d VB,et al.Collagen type 1retards tube formation by human microvascular endothelial cells in a fibrin matrix[J].Angiogenesis,2002,5(4):257-265.
59.Wang L,Shi Q,Dai J,et al.Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold[J].J Orthop Res,2017,36(3):1024-1034.
60.Hong LTA,Kim YM,Park HH,et al.An injectable hydrogel enhances tissue repair after spinal cord injury by promoting extracellular matrix remodeling[J].Nat Commun,2017,8(1):533.
61.Zeng CG,Xiong Y,Xie G,et al.Fabrication and evaluation of PLLA multichannel conduits with nanofibrous microstructure for the differentiation of NSCs in vitro[J].Tissue Eng Part A,2014,20(5-6):1038-1048.
62.Duan H,Ge W,Zhang A,et al.Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury[J].Proc Natl Acad Sci U S A,2015,112(43):13360-13365.
63.Zeng X,Zeng YS,Ma YH,et al.Bone marrow mesenchymal stem cells in a three-dimensional gelatin sponge scaffold attenuate inflammation,promote angiogenesis,and reduce cavity formation in experimental spinal cord injury[J].Cell Transplant,2011,20(11-12):1881-1899.
64.Shafiee A,Atala A.Printing technologies for medical applications[J].Trends Mol Med,2016,22(3):254-265.