Zhong Tianyu, Gao Yunan, Qiao Hu, Zhou Hong, Liu Yong
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Xi'an Jiaotong University, Xi'an, China; Department of Orthodontics, The Affiliated Stomatological Hospital of Xi'an Jiaotong University, Xi'an, China; Institute of Neurobiology, Xi'an Jiaotong University Health Science Center, Xi'an, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Xi'an Jiaotong University, Xi'an, China; Department of Orthodontics, The Affiliated Stomatological Hospital of Xi'an Jiaotong University, Xi'an, China.
Ann Palliat Med. 2020 Sep;9(5):2962-2969. doi: 10.21037/apm-20-460. Epub 2020 Jul 21.
The osteogenic capacity of inflammatory dental pulp stem cells (DPSCs-IPs) is reported lower than that of normal dental pulp stem cells (DPSCs-NPs). Down-regulation of Wnt4 may be the key factor affecting the osteogenic ability of DPSCs-IPs. In order to prove that the restoration of Wnt4 expression could improve the osteogenic potential of DPSCs-IPs, Wnt4 overexpressed inflammatory dental pulp stem cells (Wnt4-DPSCs-IPs) were performed to reconstruct bone defects in rats.
Human DPSCs-IPs were cultured and transfected with Wnt4 overexpression lentiviral vector. Stem cell characterization was performed by flow cytometry and induction of multidirectional differentiation. Wnt4-DPSCs-IPs were loaded onto poly (hydroxybutyrate-co-valerate) (PHBV). The compounds were engrafted into artificially-created defect in alveolar bone. The effectiveness of Wnt4-DPSCs-IPs/PHBV in bone regeneration was assessed by micro-CT and immunohistochemical staining of osteocalcin, a representative osteogenic marker.
Collecting data showed that Wnt4 overexpression didn't change stem cell characteristics of DPSCs-IPs. Wnt4-DPSCs-IPs retain osteogenic, adipogenic and chondrogenic differentiation abilities. Wnt4-DPSCs-IPs/PHBV were more effective than DPSCs-IPs/PHBV in repair of rat bone defects by 3 months' post-surgical reconstruction.
Restoration of Wnt4 expression could improve the osteogenic potential of DPSCs-IPs. Wnt4 restored DPSCs-IPs may be a feasible resource of seed cells for bone regeneration in future clinical application.
据报道，炎性牙髓干细胞（DPSCs - IPs）的成骨能力低于正常牙髓干细胞（DPSCs - NPs）。Wnt4的下调可能是影响DPSCs - IPs成骨能力的关键因素。为了证明恢复Wnt4表达可以提高DPSCs - IPs的成骨潜能，构建了Wnt4过表达的炎性牙髓干细胞（Wnt4 - DPSCs - IPs）来修复大鼠骨缺损。
培养人DPSCs - IPs并用Wnt4过表达慢病毒载体进行转染。通过流式细胞术和多向分化诱导进行干细胞特性鉴定。将Wnt4 - DPSCs - IPs接种到聚（羟基丁酸酯 - 共 - 戊酸酯）（PHBV）上。将复合物植入人工制造的牙槽骨缺损处。通过显微CT和骨钙素（一种代表性的成骨标志物）的免疫组织化学染色评估Wnt4 - DPSCs - IPs/PHBV在骨再生中的有效性。
收集的数据表明，Wnt4过表达并未改变DPSCs - IPs的干细胞特性。Wnt4 - DPSCs - IPs保留了成骨、成脂和成软骨分化能力。术后3个月重建时，Wnt4 - DPSCs - IPs/PHBV在修复大鼠骨缺损方面比DPSCs - IPs/PHBV更有效。
恢复Wnt4表达可提高DPSCs - IPs的成骨潜能。恢复Wnt4的DPSCs - IPs可能是未来临床应用中骨再生种子细胞的一种可行来源。
