PMID- 32323459 OWN - NLM STAT- MEDLINE DCOM- 20211027 LR - 20211027 IS - 1552-4965 (Electronic) IS - 1549-3296 (Linking) VI - 108 IP - 9 DP - 2020 Sep TI - A bone matrix-simulating scaffold to alleviate replicative senescence of mesenchymal stem cells during long-term expansion. PG - 1955-1967 LID - 10.1002/jbm.a.36958 [doi] AB - Replicative senescence during in vitro augmentation, which is mostly induced by the loss of physiological microenvironment, hinders the application of mesenchymal stem cells (MSCs) in the clinic. Here, we investigated whether MSCs senescence could be prevented by bio-scaffold mimicking the natural tissue matrix. Human umbilical cord mesenchymal stem cells (hUCMSCs) exhibited a senescent phenotype during a long-term passage in the conventional culture dish. To fabricate the bone matrix, a naturally based matrix composed of nano-hydroxyapatite/chitosan/poly lactide-co-glycolide (nHA/CS/PLGA) was produced. Long-term passage resulted in an obvious increase in the expression of senescence markers and a reduction in the expression of master genes involved in tissue regeneration. Functional assay confirmed that nHA/CS/PLGA scaffold preserved the proliferation and differentiation of hUCMSCs even after being passaged 27 times. Moreover, in vivo ectopic bone formation assay revealed that the bone formation of hUCMSCs cultured on the nano-scaffolds for the long term was as robust as the cells in the early passage. In summary, our results demonstrate that nHA/CS/PLGA scaffold effectively preserves the stemness and youth of hUCMSCs in the long-term passage. Taken advantage of its compatibility and bioactivity, nHA/CS/PLGA scaffold is of great potential in large-scale expansion of MSCs for stem cell therapy and tissue engineering. CI - (c) 2020 Wiley Periodicals, Inc. FAU - Su, Xiaoxia AU - Su X AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Jing, Huan AU - Jing H AD - Department of Stomatology, Bethune International Peace Hospital, Shijiazhuang, China. FAU - Yu, Wenting AU - Yu W AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Lei, Fengzhen AU - Lei F AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Wang, Rui AU - Wang R AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Hu, Cheng AU - Hu C AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Li, Mujia AU - Li M AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Lin, Tingting AU - Lin T AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Zhou, Hong AU - Zhou H AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Wang, Fei AU - Wang F AD - Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, Department of Orthodontics, College of Stomatology, Xi'an Jiaotong University, Xi'an, China. FAU - Liao, Li AU - Liao L AUID- ORCID: 0000-0003-0030-1009 AD - State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China. AD - State Key Laboratory of Oral Disease, West China School of Stomatology, Sichuan University, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200502 PL - United States TA - J Biomed Mater Res A JT - Journal of biomedical materials research. Part A JID - 101234237 SB - IM MH - Animals MH - Bone Matrix/*chemistry MH - Cell Culture Techniques/methods MH - Cell Proliferation MH - Cells, Cultured MH - Cellular Senescence MH - Humans MH - Mesenchymal Stem Cells/*cytology MH - Mice, Inbred BALB C MH - Mice, Nude MH - Osteogenesis MH - Tissue Engineering MH - Tissue Scaffolds/*chemistry OTO - NOTNLM OT - biomaterials OT - differentiation OT - mesenchymal stem cells OT - microenvironment OT - proliferation OT - senescence EDAT- 2020/04/24 06:00 MHDA- 2021/10/28 06:00 CRDT- 2020/04/24 06:00 PHST- 2020/01/21 00:00 [received] PHST- 2020/04/15 00:00 [revised] PHST- 2020/04/19 00:00 [accepted] PHST- 2020/04/24 06:00 [pubmed] PHST- 2021/10/28 06:00 [medline] PHST- 2020/04/24 06:00 [entrez] AID - 10.1002/jbm.a.36958 [doi] PST - ppublish SO - J Biomed Mater Res A. 2020 Sep;108(9):1955-1967. doi: 10.1002/jbm.a.36958. Epub 2020 May 2.