《中国康复理论与实践》 ›› 2021, Vol. 27 ›› Issue (6): 677-686.doi: 10.3969/j.issn.1006-9771.2021.06.008
收稿日期:
2019-11-04
修回日期:
2021-04-14
出版日期:
2021-06-25
发布日期:
2021-06-21
通讯作者:
漆伟
E-mail:qiwei200@126.com
作者简介:
漆国栋(1993-),男,汉族,重庆市人,硕士,医师,主要研究方向:骨与神经组织损伤后修复方面的研究|漆伟(1966-),男,汉族,重庆市人,硕士,主任医师,主要研究方向:骨与神经组织损伤后修复方面的研究。
基金资助:
Guo-dong QI1,2,Qiong JIANG2,Ya-min WU3,Wei QI1()
Received:
2019-11-04
Revised:
2021-04-14
Published:
2021-06-25
Online:
2021-06-21
Contact:
Wei QI
E-mail:qiwei200@126.com
Supported by:
摘要: 以脊髓组织工程中的种子细胞和生物支架存在的问题为切入点,综述近期实验研究进展。 检索建库至2021年3月中国知网、万方、PubMed和Web of Science数据库中的相关文献,并对种子细胞、生物支架和种子细胞-生物支架复合的问题及进展进行综述。 种子细胞的问题在于致癌性、免疫排斥、伦理道德和移植后低存活率与分化率,现研究多集中于探索新细胞种类、基因转染、多细胞共移植和移植前预处理。生物支架的问题在于单一材料选择无法同时满足不同需求,且传统工艺也无法更好地模拟脊髓内部结构,因此,新型复合材料与新工艺成为研究热点。种子细胞-生物支架复合的核心问题在于不同种子细胞与生物支架复合的效果不一,现研究多致力于持续探索适宜的新复合模式,并尝试引入生物制剂等因素。 脊髓组织工程有潜力彻底改变脊髓损伤治疗路径,现阶段实验研究主要以解决脊髓组织工程中的种子细胞与生物支架各自问题作为基础,进而深入探索二者适宜的复合模式,以此为临床应用提供更多基础证据。
中图分类号:
漆国栋,江琼,伍亚民,漆伟. 种子细胞与生物支架在脊髓组织工程中的实验研究进展[J]. 《中国康复理论与实践》, 2021, 27(6): 677-686.
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.
表1
种子细胞中的干细胞和周围神经细胞列举"
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[ |
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[ | |
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[ | |
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[ | |
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[ | |
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[ |
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[ |
表2
传统生物支架实验研究列举"
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ |
表3
近期脊髓组织工程种子细胞-生物支架复合模式列举"
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ | |
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[ |
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[ |
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