目的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。方法检索建库至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...目的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。方法检索建库至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。结果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。结论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。展开更多
The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ.Platelet-derived growth factor（PDGF） has been...The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ.Platelet-derived growth factor（PDGF） has been shown to promote the migration of bone marrow stromal cells;however,cytokines need to be released at a steady rate to maintain a stable concentration in vivo.Therefore,new methods are needed to maintain an optimal concentration of cytokines over an extended period of time to effectively promote seed cell localization,proliferation and differentiation.In the present study,a partition-type tubular scaffold matching the anatomical features of the thoracic 8–10 spinal cord of the rat was fabricated using chitosan and then subsequently loaded with chitosan-encapsulated PDGF-BB microspheres（PDGF-MSs）.The PDGF-MS-containing scaffold was then examined in vitro for sustained-release capacity,biocompatibility,and its effect on neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells（MUSE-NPCs）.We found that pre-freezing for 2 hours at-20°C significantly increased the yield of partition-type tubular scaffolds,and 30 μL of 25% glutaraldehyde ensured optimal crosslinking of PDGF-MSs.The resulting PDGF-MSs cumulatively released 52% of the PDGF-BB at 4 weeks in vitro without burst release.The PDGF-MS-containing tubular scaffold showed suitable biocompatibility towards MUSE-NPCs and could promote the directional migration and growth of these cells.These findings indicate that the combination of a partition-type tubular scaffold,PDGF-MSs and MUSENPCs may be a promising model for the fabrication of tissue-engineered spinal cord grafts.展开更多
文摘目的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。方法检索建库至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。结果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。结论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。
基金supported by the Natural Science Foundation of China,No.81501610,81350030the Priority Academic Program Development of Jiangsu Higher Education Institutes of China
文摘The best tissue-engineered spinal cord grafts not only match the structural characteristics of the spinal cord but also allow the seed cells to grow and function in situ.Platelet-derived growth factor（PDGF） has been shown to promote the migration of bone marrow stromal cells;however,cytokines need to be released at a steady rate to maintain a stable concentration in vivo.Therefore,new methods are needed to maintain an optimal concentration of cytokines over an extended period of time to effectively promote seed cell localization,proliferation and differentiation.In the present study,a partition-type tubular scaffold matching the anatomical features of the thoracic 8–10 spinal cord of the rat was fabricated using chitosan and then subsequently loaded with chitosan-encapsulated PDGF-BB microspheres（PDGF-MSs）.The PDGF-MS-containing scaffold was then examined in vitro for sustained-release capacity,biocompatibility,and its effect on neural progenitor cells differentiated in vitro from multilineage-differentiating stress-enduring cells（MUSE-NPCs）.We found that pre-freezing for 2 hours at-20°C significantly increased the yield of partition-type tubular scaffolds,and 30 μL of 25% glutaraldehyde ensured optimal crosslinking of PDGF-MSs.The resulting PDGF-MSs cumulatively released 52% of the PDGF-BB at 4 weeks in vitro without burst release.The PDGF-MS-containing tubular scaffold showed suitable biocompatibility towards MUSE-NPCs and could promote the directional migration and growth of these cells.These findings indicate that the combination of a partition-type tubular scaffold,PDGF-MSs and MUSENPCs may be a promising model for the fabrication of tissue-engineered spinal cord grafts.
