title: Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats.
abstract: The functions of mesenchymal stem cells (MSCs) appear to decline with age due to cellular senescence, which could reduce the efficacy of MSCs-based therapies. Recently, MSCs have been identified in the nucleus pulposus, which offers great potential for intervertebral disc (IVD) repair. However, this potential might be affected by the senescence of nucleus pulposus MSCs (NPMSCs), but whether or not this exists remains unknown. The aim of this study was to investigate the age-related changes in NPMSCs. NPMSCs isolated from young (3-month-old) and old (14-month-old) Sprague-Dawley rats were cultured in vitro. Differences in morphology, proliferation, colony formation, multilineage differentiation, cell cycle, and expression ofβ-galactosidase (SA-β-gal) and senescent markers (p53, p21, and p16) were compared between groups. Both young and old NPMSCs fulfilled the criteria for definition as MSCs. Moreover, young NPMSCs presented better proliferation, colony-forming, and multilineage differentiation capacities than old NPMSCs. Old NPMSCs displayed senescent features, including significantly increased G0/G1 phase arrest, increased SA-β-gal expression, decreased S phase entry, and significant p53-p21-pRB pathway activation. Therefore, this is the first study demonstrating that senescent NPMSCs accumulate in IVD with age. The efficacy of NPMSCs is compromised by donor age, which should be taken into consideration prior to clinical application.
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Yachao
authors.identifier: 0000-0001-9002-8485
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, The 306th Hospital of People's Liberation Army, Beijing, China.
authors.forename: Zhiwei
authors.identifier: 0000-0002-0601-3318
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Laboratory Medicine, Children's Hospital of Hebei Province, Shijiazhuang, Hebei, China.
authors.forename: Shanshan
authors.identifier: 0000-0002-8665-3875
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Yaohong
authors.identifier: 0000-0002-7393-2779
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Longgang
authors.identifier: 0000-0002-7021-1810
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Linghan
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Deli
authors.identifier: 0000-0001-5032-2567
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Qing
authors.identifier: 0000-0002-5712-0762
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Orthopaedics, Navy General Hospital, Beijing, China.
authors.forename: Dike
authors.identifier: 0000-0002-9642-3096
authors.initials: D
authors.lastname: Ruan