Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats

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...

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Main Authors: Yachao Zhao, Zhiwei Jia, Shanshan Huang, Yaohong Wu, Longgang Liu, Linghan Lin, Deli Wang, Qing He, Dike Ruan
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/6761572
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author Yachao Zhao
Zhiwei Jia
Shanshan Huang
Yaohong Wu
Longgang Liu
Linghan Lin
Deli Wang
Qing He
Dike Ruan
author_facet Yachao Zhao
Zhiwei Jia
Shanshan Huang
Yaohong Wu
Longgang Liu
Linghan Lin
Deli Wang
Qing He
Dike Ruan
author_sort Yachao Zhao
collection DOAJ
description 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 of β-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.
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publishDate 2017-01-01
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spelling doaj-art-a0a52b305b2345ccbedd4350fefb81292025-02-03T06:08:13ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/67615726761572Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in RatsYachao Zhao0Zhiwei Jia1Shanshan Huang2Yaohong Wu3Longgang Liu4Linghan Lin5Deli Wang6Qing He7Dike Ruan8Department of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, The 306th Hospital of People’s Liberation Army, Beijing, ChinaDepartment of Laboratory Medicine, Children’s Hospital of Hebei Province, Shijiazhuang, Hebei, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaDepartment of Orthopaedics, Navy General Hospital, Beijing, ChinaThe 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 of β-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.http://dx.doi.org/10.1155/2017/6761572
spellingShingle Yachao Zhao
Zhiwei Jia
Shanshan Huang
Yaohong Wu
Longgang Liu
Linghan Lin
Deli Wang
Qing He
Dike Ruan
Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
Stem Cells International
title Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
title_full Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
title_fullStr Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
title_full_unstemmed Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
title_short Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats
title_sort age related changes in nucleus pulposus mesenchymal stem cells an in vitro study in rats
url http://dx.doi.org/10.1155/2017/6761572
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