种子细胞与生物支架在脊髓组织工程中的实验研究进展

doi:10.3969/j.issn.1006-9771.2021.06.008

Abstract

Abstract: Objective

To explore the problems of seed cells and biological scaffolds in spinal cord tissue engineering, and review the recent experimental research.

Methods

Related literatures were searched in CNKI, Wangfang data, PubMed and Web of Science from establishment to March, 2021, and the problems and progress of seed cells, biological scaffolds and their combination were reviewed.

Results

The problems of seed cells are carcinogenicity, immune rejection, ethics, low survival rate and differentiation rate after transplantation, and current researches focus on exploring new cell types, gene transfection, cell co-transplantation and pretreatment before transplantation. The problems of biological scaffold are that a single material selection cannot meet different needs, and the traditional technology cannot simulate the internal structure of spinal cord well. There were more researches focusing on new composite materials and new technology. The core problem of their combination is that the effects of different cell and scaffold combinations are different, and the current researches are mostly devoted to the continuous exploration of suitable composite mode, and try to introduce biological agents and other factors.

Conclusion

Spinal cord tissue engineering has the potential to completely change the therapeutic pathway of spinal cord injury. Current experimental researches mainly base on solving the problems of seed cells and biological scaffolds of spinal cord tissue engineering, and further explore the appropriate composite mode of seed cells and biological scaffolds, so as to provide more basic evidence for its clinical application.

Key words: spinal cord tissue engineering, spinal cord injury, seed cells, biological scaffolds, experiment research, review

CLC Number:

R651.2

Guo-dong QI,Qiong JIANG,Ya-min WU,Wei QI. Experimental Advance in Seed Cells and Biological Scaffolds for Spinal Cord Tissue Engineering (review)[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2021, 27(6): 677-686.

Figures/Tables 4

细胞	支架	体外	体内	结论
子宫内膜干细胞	纤维蛋白水凝胶	未提及	√	支架上的人子宫内膜干细胞生长良好，可促进大鼠脊髓损伤后的运动功能恢复^[67]
子宫内膜干细胞	自组装多肽	√	√	含有层粘连蛋白长基序的肽纳米纤维具有增加神经发生和减少星形胶质细胞的作用^[68]
神经干细胞	壳聚糖-明胶	√	未提及	该支架表面层能显著促进神经干细胞的黏附与生长，而且可以促进向高蛋白、搞基因表达的神经元与星形胶质细胞分化^[69]
神经干细胞	胶原蛋白	√	√	附着在支架上的细胞可更多分化成神经元，且移植到完全切断大鼠脊髓后更多细胞迁移到损伤中心和新生神经元出现在损伤部位^[70]
间充质干细胞	丝-明胶海绵	√	√	具有较高的细胞活性，具有良好的细胞分布和表型，在移植后具有较强的生物相容性^[71]
间充质干细胞	肽系水凝胶	√	√	在体外显著提高细胞存活率、黏附与生长。在体内抑制继发性损伤因素，包括炎症反应和星形胶质细胞过度活动^[72]
脂肪干细胞	纤维蛋白	√	√	种植在纤维蛋白支架上的脂肪干细胞能产生更多的功能性神经营养因子和血管生成因子，增强轴突再生距离^[73]
脂肪干细胞	结冷胶水凝胶	√	√	脂肪干细胞和嗅鞘细胞可以再水凝胶中共培养，诱导更强健的神经突起生长。体内移植后，可导致显著的运动改善^[74]
诱导性多功能干细胞	丙烯酸明胶	√	√	在体外神经突起生长旺盛，神经元分化明显。在体内减少空腔面积与胶原沉积，通过减少活化的巨噬细胞/小胶质细胞来减轻炎症，并且显著抑制胶质瘢痕及促进轴突再生^[75]
诱导性多功能干细胞	层粘连蛋白水凝胶	√	√	在体外支架上细胞可显著表达神经特异性蛋白。复合物植入慢性损伤模型后宿主轴突、星形胶质细胞和血管生长到复合物中，但统计学上没有显著改善运动恢复^[76]
施万细胞	聚乳酸-羟基乙酸	未提及	√	细胞在支架上分布与增殖良好，能显著改善脊髓的恢复^[77]
施万细胞	聚己内酯	√	√	扫描电镜结果表明，细胞在支架上生长良好。此外，移植可减少损伤腔的体积，提高大鼠运动功能的恢复^[78]
嗅鞘细胞	柞蚕丝素蛋白	√	未提及	丝素蛋白纳米纤维可以调控嗅鞘细胞的形态、黏附、扩散、基因和蛋白的表达及迁移^[79]
嗅鞘细胞	胶原	未提及	√	当胶原支架上种植嗅鞘细胞后，嗅鞘细胞可以在支架上迁徙并形成髓鞘从而引起轴突再生，最终导致前肢功能改善^[80]

References 85

1	KUMAR R, LIM J, MEKARY R A, et al. Traumatic spinal injury: global epidemiology and worldwide volume [J]. World Neurosurg. 2018, 113: e345-e363.
2	PINCHI E, FRATI A, CANTATORE S, et al. Acute spinal cord injury: a systematic review investigating miRNA families involved [J]. Int J Mol Sci, 2019, 20(8): 1841.
3	ANWAR M A, SHEHABI T S A, EID A H. Inflammogenesis of secondary spinal cord injury [J]. Front Cell Neurosci, 2016, 10: 98.
4	UMEBAYASHI D, NATSUME A, TAKEUCHI H, et al. Blockade of gap junction hemichannel protects secondary spinal cord injury from activated microglia-mediated glutamate exitoneurotoxicity [J]. J Neurotrauma, 2014, 31(24): 1967-1974.
5	DAWSON T M, DAWSON V L. Mitochondrial mechanisms of neuronal cell death: potential therapeutics [J]. Annu Rev Pharmacol Toxicol, 2017, 57: 437-454.
6	BAKHSHANDEH B, ZARRINTAJ P, OFTADEH M O, et al. Tissue engineering; strategies, tissues, and biomaterials [J]. Biotechnol Genet Eng Rev, 2017, 33(2): 144-172.
7	RASPA A, PUGLIESE R, MALEKI M, et al. Recent therapeutic approaches for spinal cord injury [J]. Biotechnol Bioeng, 2016, 113(2): 253-259.
8	XIAO Z, TANG F, TANG J, et al. One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients [J]. Sci China Life Sci, 2016, 59(7): 647-655.
9	THEODORE N, HLUBEK R, DANIELSON J, et al. First human implantation of a bioresorbable polymer scaffold for acute traumatic spinal cord injury: a clinical pilot study for safety and feasibility [J]. Neurosurgery, 2016, 79(2): E305-E312.
10	LEVI A D, ANDERSON K D, OKONKWO D O, et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury [J]. J Neurotrauma, 2019, 36(6): 891-902.
11	BARTLETT R D, BURLEY S, IP M, et al. Cell therapies for spinal cord injury: trends and challenges of current clinical trials [J]. Neurosurgery, 2020, 87(4): E456-E472.
12	BOTTAI D, CIGOGNINI D, MADASCHI L, et al. Embryonic stem cells promote motor recovery and affect inflammatory cell infiltration in spinal cord injured mice [J]. Exp Neurol, 2010, 223(2): 452-463.
13	KEIRSTEAD H S, NISTOR G, BERNAL G, et al. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury [J]. J Neurosci, 2005, 25(19): 4694-4705.
14	PFEIFER K, VROEMEN M, BLESCH A, et al. Adult neural progenitor cells provide a permissive guiding substrate for corticospinal axon growth following spinal cord injury [J]. Eur J Neurosci, 2004, 20(7): 1695-1704.
15	MORITA T, SASAKI M, KATAOKA-SASAKI Y, et al. Intravenous infusion of mesenchymal stem cells promotes functional recovery in a model of chronic spinal cord injury [J]. Neuroscience, 2016, 335: 221-231.
16	CHUNG H J, CHUNG W H, LEE J H, et al. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats [J]. J Vet Sci, 2016, 17(1): 97-102.
17	WANG Y, LIU H, MA H. Intrathecally transplanting mesenchymal stem cells (MSCs) activates ERK1/2 in spinal cords of ischemia-reperfusion injury rats and improves nerve function [J]. Med Sci Monit, 2016, 22: 1472-1479.
18	KINGHAM P J, KOLAR M K, NOVIKOVA L N, et al. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair [J]. Stem Cells Dev, 2014, 23(7): 741-754.
19	KOLAR M K, KINGHAM P J, NOVIKOVA L N, et al. The therapeutic effects of human adipose-derived stem cells in a rat cervical spinal cord injury model [J]. Stem Cells Dev, 2014, 23(14): 1659-1674.
20	ROMANYUK N, AMEMORI T, TURNOVCOVA K, et al. Beneficial effect of human induced pluripotent stem cell-derived neural precursors in spinal cord injury repair [J]. Cell Transplant, 2015, 24(9): 1781-1797.
21	AMEMORI T, RUZICKA J, ROMANYUK N, et al. Comparison of intraspinal and intrathecal implantation of induced pluripotent stem cell-derived neural precursors for the treatment of spinal cord injury in rats [J]. Stem Cell Res Ther, 2015, 6: 257.
22	YUI S, FUJITA N, CHUNG C S, et al. Olfactory ensheathing cells (OECs) degrade neurocan in injured spinal cord by secreting matrix metalloproteinase-2 in a rat contusion model [J]. Jpn J Vet Res, 2014, 62(4): 151-162.
23	KHANKAN R R, GRIFFIS K G, HAGGERTY-SKEANS J R, et al. Olfactory ensheathing cell transplantation after a complete spinal cord transection mediates neuroprotective and immunomodulatory mechanisms to facilitate regeneration [J]. J Neurosci, 2016, 36(23): 6269-6286.
24	AZANCHI R, BERNAL G, GUPTA R, et al. Combined demyelination plus Schwann cell transplantation therapy increases spread of cells and axonal regeneration following contusion injury [J]. J Neurotrauma, 2004, 21(6): 775-788.
25	WILLIAMS R R, HENAO M, PEARSE D D, et al. Permissive Schwann cell graft/spinal cord interfaces for axon regeneration [J]. Cell Transplant, 2015, 24(1): 115-131.
26	MIURA K, OKADA Y, AOI T, et al. Variation in the safety of induced pluripotent stem cell lines [J]. Nat Biotechnol, 2009, 27(8): 743-745.
27	SALEWSKI R P, MITCHELL R A, SHEN C, et al. Transplantation of neural stem cells clonally derived from embryonic stem cells promotes recovery after murine spinal cord injury [J]. Stem Cells Dev, 2015, 24(1): 36-50.
28	TEH D B L, PRASAD A, JIANG W, et al. Driving neurogenesis in neural stem cells with high sensitivity optogenetics [J]. Neuromolecular Med, 2020, 22(1): 139-149.
29	ANTONIOS J P, FARAH G J, CLEARY D R, et al. Immunosuppressive mechanisms for stem cell transplant survival in spinal cord injury [J]. Neurosurg Focus, 2019, 46(3): E9.
30	叶佳美,胡晓敏,王丽群,等. 间充质干细胞治疗脊髓损伤的可视化分析[J]. 中国康复理论与实践, 2020, 26(4): 400-406.
	YE J M, HU X M, WANG L Q, et al. Researches on mesenchymal stem cells for treatment of spinal cord injury: a visualization analysis [J]. Chin J Rehabil Theory Pract, 2020, 26(4): 400-406.
31	HAKIM R, COVACU R, ZACHARIADIS V, et al. Mesenchymal stem cells transplanted into spinal cord injury adopt immune cell-like characteristics [J]. Stem Cell Res Ther, 2019, 10(1): 115.
32	YAMANAKA S, TAKAHASHI K. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors [J]. Cell, 2006, 126(4): 663-676.
33	QIN C, GUO Y, YANG D G, et al. Induced pluripotent stem cell transplantation improves locomotor recovery in rat models of spinal cord injury: a systematic review and meta-analysis of randomized controlled trials [J]. Cell Physiol Biochem, 2018, 47(5): 1835-1852.
34	TSUJI O, SUGAI K, YAMAGUCHI R, et al. Concise Review: laying the groundwork for a first-in-human study of an induced pluripotent stem cell-based intervention for spinal cord injury [J]. Stem Cells, 2019, 37(1): 6-13.
35	TANG L, LU X, ZHU R, et al. Adipose-derived stem cells expressing the neurogenin-2 promote functional recovery after spinal cord injury in rat [J]. Cell Mol Neurobiol, 2016, 36(5): 657-667.
36	SHI W, QUE Y, LV D, et al. Overexpression of TG2 enhances the differentiation of ectomesenchymal stem cells into neuron‑like cells and promotes functional recovery in adult rats following spinal cord injury [J]. Mol Med Rep, 2019, 20(3): 2763-2773.
37	ALLAHDADI K J, DE SANTANA T A, SANTOS G C, et al. IGF-1 overexpression improves mesenchymal stem cell survival and promotes neurological recovery after spinal cord injury [J]. Stem Cell Res Ther, 2019, 10(1): 146.
38	ZHANG J, CHEN H, DUAN Z, et al. The effects of co-transplantation of olfactory ensheathing cells and Schwann cells on local inflammation environment in the contused spinal cord of rats [J]. Mol Neurobiol, 2017, 54(2): 943-953.
39	SUN L, WANG F, CHEN H, et al. Co-transplantation of human umbilical cord mesenchymal stem cells and human neural stem cells improves the outcome in rats with spinal cord injury [J]. Cell Transplant, 2019, 28(7): 893-906.
40	GOMES E D, MENDES S S, ASSUNÇÃO-SILVA R C, et al. Co-transplantation of adipose tissue-derived stromal cells and olfactory ensheathing cells for spinal cord injury repair [J]. Stem Cells, 2018, 36(5): 696-708.
41	ZHILAI Z, BILING M, SUJUN Q, et al. Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury [J]. Brain Res, 2016, 1642: 426-435.
42	SONG Y Y, PENG C G, YE X B. Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats [J]. Genet Mol Res, 2015, 14(4): 19136-19143.
43	漆国栋,伍亚民,漆伟,等. 黄芪总皂甙对Wnt/β-catenin信号通路及神经干细胞分化的影响[J]. 中国康复理论与实践, 2018, 24(11): 1264-1270.
	QI G D, WU Y M, QI W. Effects of total saponins of astragalus on neural stem cells differentiating and Wnt/β-catenin signaling pathway [J]. Chin J Rehabil Theory Pract, 2018, 24(11): 1264-1270.
44	BARTLETT R D, CHOI D, PHILLIPS J B. Biomechanical properties of the spinal cord: implications for tissue engineering and clinical translation [J]. Regen Med, 2016, 11(7): 659-673.
45	SUBRAMANIAN A, KRISHNAN U M, SETHURAMAN S. Development of biomaterial scaffold for nerve tissue engineering: biomaterial mediated neural regeneration [J]. J Biomed Sci, 2009, 16: 108.
46	BREEN B A, KRASKIEWICZ H, RONAN R, et al. Therapeutic effect of neurotrophin-3 treatment in an injectable collagen scaffold following rat spinal cord hemisection injury [J]. ACS Biomater Sci Eng, 2017, 3(7): 1287-1295.
47	SHI Q, GAO W, HAN X, et al. Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model [J]. Sci China Life Sci, 2014, 57(2): 232-240.
48	CHEDLY J, SOARES S, MONTEMBAULT A, et al. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration [J]. Biomaterials, 2017, 138: 91-107.
49	YANG Z, ZHANG A, DUAN H, et al. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury [J]. Proc Natl Acad Sci U S A, 2015, 112(43): 13354-13359.
50	KING V R, ALOVSKAYA A, WEI D Y, et al. The use of injectable forms of fibrin and fibronectin to support axonal ingrowth after spinal cord injury [J]. Biomaterials, 2010, 31(15): 4447-4456.
51	JOHNSON P J, PARKER S R, SAKIYAMA-ELBERT S E. Fibrin-based tissue engineering scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury [J]. J Biomed Mater Res A, 2010, 92(1): 152-163.
52	LEVIN B, REDMOND S L, RAJKHOWA R, et al. Utilising silk fibroin membranes as scaffolds for the growth of tympanic membrane keratinocytes, and application to myringo plasty surgery [J]. J Laryngol Otol, 2013, 127(1): S13-S20.
53	KWIECIEN J M, ZHANG L, YARON J R, et al. Local serpin treatment via chitosan-collagen hydrogel after spinal cord injury reduces tissue damage and improves neurologic function [J]. J Clin Med, 2020, 9(4): 1221.
54	LI X, ZHANG C, HAGGERTY A E, et al. The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord [J]. Biomaterials, 2020, 245: 119978.
55	NUNE M, KRISHNAN U M, SETHURAMAN S. PLGA nanofibers blended with designer self-assembling peptides for peripheral neural regeneration [J]. Mater Sci Eng C Mater Biol Appl, 2016, 62: 329-337.
56	AHI Z B, ASSUNÇÃO-SILVA R C, SALGADO A J, et al. A combinatorial approach for spinal cord injury repair using multifunctional collagen-based matrices: development, characterization and impact on cell adhesion and axonal growth [J]. Biomed Mater, 2020, 15(5): 055024.
57	SCHAUB N J, JOHNSON C D, COOPER B, et al. Electrospun fibers for spinal cord injury research and regeneration [J]. J Neurotrauma, 2016, 33(15): 1405-1415.
58	VIGANI B, ROSSI S, SANDRI G, et al. Design and criteria of electrospun fibrous scaffolds for the treatment of spinal cord injury [J]. Neural Regen Res, 2017, 12(11): 1786-1790.
59	YAN H, WANG Y, LI L, et al. A micropatterned conductive electrospun nanofiber mesh combined with electrical stimulation for synergistically enhancing differentiation of rat neural stem cells [J]. J Mater Chem B, 2020, 8(13): 2673-2688.
60	CNOPS V, CHIN J S, MILBRETA U, et al. Biofunctional scaffolds with high packing density of aligned electrospun fibers support neural regeneration [J]. J Biomed Mater Res A, 2020, 108(12): 2473-2483.
61	BAGARIA V, BHANSALI R, PAWAR P. 3D printing-creating a blueprint for the future of orthopedics: current concept review and the road ahead! [J]. J Clin Orthop Trauma, 2018, 9(3): 207-212.
62	KOFFLER J, ZHU W, QU X, et al. Biomimetic 3D-printed scaffolds for spinal cord injury repair [J]. Nat Med, 2019, 25(2): 263-269.
63	SUN Y, YANG C, ZHU X, et al. 3D printing collagen/chitosan scaffold ameliorated axon regeneration and neurological recovery after spinal cord injury [J]. J Biomed Mater Res A, 2019, 107(9): 1898-1908.
64	SOARES S, BOXBERG Y VON, NOTHIAS F. Repair strategies for traumatic spinal cord injury, with special emphasis on novel biomaterial-based approaches [J]. Rev Neurol (Paris), 2020, 176(4): 252-260.
65	WILEMS T S, PARDIECK J, IYER N, et al. Combination therapy of stem cell derived neural progenitors and drug delivery of anti-inhibitory molecules for spinal cord injury [J]. Acta Biomater, 2015, 28: 23-32.
66	QIU X C, JIN H, ZHANG R Y, et al. Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transection [J]. Stem Cell Res Ther, 2015, 6: 105.
67	JALALI MONFARED M, NASIRINEZHAD F, EBRAHIMI-BAROUGH S, et al. Transplantation of miR-219 overexpressed human endometrial stem cells encapsulated in fibrin hydrogel in spinal cord injury [J]. J Cell Physiol, 2019, 234(10): 18887-18896.
68	TAVAKOL S, SABER R, HOVEIZI E, et al. Self-assembling peptide nanofiber containing long motif of laminin induces neural differentiation, tubulin polymerization, and neurogenesis: in vitro, ex vivo, and in vivo studies [J]. Mol Neurobiol, 2016, 53(8): 5288-5299.
69	WANG S, GUAN S, LI W, et al. 3D culture of neural stem cells within conductive PEDOT layer-assembled chitosan/gelatin scaffolds for neural tissue engineering [J]. Mater Sci Eng C Mater Biol Appl, 2018, 93: 890-901.
70	LIU W, XU B, XUE W, et al. A functional scaffold to promote the migration and neuronal differentiation of neural stem/progenitor cells for spinal cord injury repair [J]. Biomaterials, 2020, 243: 119941.
71	LI G, CHE M T, ZHANG K, et al. Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury [J]. Biomaterials, 2016, 83: 233-248
72	LI L M, HAN M, JIANG X C, et al. Peptide-tethered hydrogel scaffold promotes recovery from spinal cord transection via synergism with mesenchymal stem cells [J]. ACS Appl Mater Interfaces, 2017, 9(4): 3330-3342.
73	KINGHAM P J, KOLAR M K, NOVIKOVA L N, et al. Stimulating the neurotrophic and angiogenic properties of human adipose-derived stem cells enhances nerve repair [J]. Stem Cells Dev, 2014, 23(7): 741-754.
74	GOMES E D, MENDES S S, LEITE-ALMEIDA H, et al. Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model [J]. Biomaterials, 2016, 105: 38-51.
75	FAN L, LIU C, CHEN X, et al. Directing induced pluripotent stem cell derived neural stem cell fate with a three-dimensional biomimetic hydrogel for spinal cord injury repair [J]. ACS Appl Mater Interfaces, 2018, 10(21): 17742-17755.
76	RUZICKA J, ROMANYUK N, JIRAKOVA K, et al. The effect of iPS-derived neural progenitors seeded on laminin-coated pHEMA-MOETACl hydrogel with dual porosity in a rat model of chronic spinal cord injury[J]. Cell Transplant, 2019, 28(4): 400-412.
77	SUN F, SHI T, ZHOU T, et al. 3D poly (lactic-co-glycolic acid) scaffolds for treating spinal cord injury [J]. J Biomed Nanotechnol, 2017, 13(3): 290-302.
78	ZHOU X, SHI G, FAN B, et al. Polycaprolactone electrospun fiber scaffold loaded with iPSCs-NSCs and ASCs as a novel tissue engineering scaffold for the treatment of spinal cord injury [J]. Int J Nanomedicine, 2018, 13: 6265-6277.
79	FAN Z, SHEN Y, ZHANG F, et al. Control of olfactory ensheathing cell behaviors by electrospun silk fibroin fibers [J]. Cell Transplant, 2013, 1: S39-50.
80	ALTINOVA H, MÖLLERS S, DEUMENS R, et al. Functional recovery not correlated with axon regeneration through olfactory ensheathing cell-seeded scaffolds in a model of acute spinal cord injury [J]. Tissue Eng Regen Med, 2016, 13(5): 585-600.
81	XING H, REN X, YIN H, et al. Construction of a NT-3 sustained-release system cross-linked with an acellular spinal cord scaffold and its effects on differentiation of cultured bone marrow mesenchymal stem cells [J]. Mater Sci Eng C Mater Biol Appl, 2019, 104: 109902.
82	LI X, ZHAO Y, CHENG S, et al. Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair [J]. Biomaterials, 2017, 137: 73-86.
83	LI X, FAN C, XIAO Z, et al. A collagen microchannel scaffold carrying paclitaxel-liposomes induces neuronal differentiation of neural stem cells through Wnt/β-catenin signaling for spinal cord injury repair [J]. Biomaterials. 2018, 183: 114-127.
84	杨明亮,李建军,李强,等. 脊柱脊髓损伤临床及康复治疗路径实施方案[J]. 中国康复理论与实践, 2012, 18(8): 791-796.
	YANG M L, LI J J, LI Q, et al. Clinic and rehabilitation pathway recommendation for spine and spinal cord injury [J]. Chin J Rehabil Theory Pract, 2012, 18(8): 791-796.
85	JI W C, LI M, JIANG W T, et al. Protective effect of brain-derived neurotrophic factor and neurotrophin-3 overexpression by adipose-derived stem cells combined with silk fibroin/chitosan scaffold in spinal cord injury [J]. Neurol Res, 2020, 42(5): 361-371.

种类	名称	来源	机制研究
干细胞	胚胎干细胞	早期胚胎、原始性腺	通过减少损伤部位巨噬细胞的数量，显著减轻损伤后的炎症反应^[12]；移植后出现大量的髓鞘再生^[13]
	神经干细胞	脑室下层、海马齿状回	可分化为神经元，取代受损的神经元，与周围神经系统建立正确的突触联系^[14]；可分化为胶质细胞，减少胶质瘢痕，增强神经营养支持和保护作用^[15]
	间充质干细胞	骨髓、骨膜、脐带血等	提高脑源性神经营养因子和神经生长因子的水平^[16]；鞘内移植可激活细胞外调节蛋白激酶1/2改善部分功能及抑制细胞凋亡^[17]
	脂肪干细胞	脂肪组织	激活转录因子3和生长相关蛋白43在背根神经节过度表达，凋亡蛋白表达明显降低^[18]；改变胶质瘢痕结构，降低星形胶质细胞密度，刺激轴突出芽^[19]
	诱导性多功能干细胞	皮肤等任何体细胞	可分化为多巴胺能神经元、中间神经元、胆碱乙酰转移酶阳性运动神经元和5-羟色胺能神经元^[20]；可保留更多的脑灰质和白质，增加轴突出芽，减少星形胶质细胞^[21]
周围神经细胞	嗅鞘细胞	嗅神经、嗅球、嗅黏膜	分泌基质金属蛋白酶-2降解抑制轴突再生的蛋白多糖^[22]；可促进胶质瘢痕边界的形成，保护局部神经元和轴突，减轻免疫细胞的浸润^[23]
周围神经细胞	施万细胞	神经纤维	分泌多种神经营养因子促进损伤神经元和轴突的存活^[24]；能刺激髓鞘再生并包裹再生轴突^[25]

材料	工艺	效果
胶原蛋白	水凝胶	在损伤部位抑制胶质瘢痕、减少炎症及增加神经元数量，可显著提高伤后4周和6周的功能恢复^[46]
胶原蛋白	冷冻干燥	可提高脊髓半切模型术后的生存率，促进运动功能恢复并引导神经纤维生长^[47]
壳聚糖	水凝胶	促进脊髓组织和血管重建，纤维胶质瘢痕减少，且能调节炎症反应^[48]
壳聚糖	冷冻干燥	在完全切除大鼠胸髓的5 mm间隙中，吸引内源性神经干细胞进入损伤区，形成功能神经网络，将上下行轴突相互连接^[49]
纤维蛋白	水凝胶	与宿主脊髓融合良好，并支持一定程度的轴突生长，连接部位可聚集一些神经元^[50]
纤维蛋白	冷冻干燥	在移植后2周和4周病变部位的神经纤维染色水平显著升高，且病变周围星形胶质细胞的积聚延迟^[51]

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Experimental Advance in Seed Cells and Biological Scaffolds for Spinal Cord Tissue Engineering (review)

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