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Article: Adipose-derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy

TitleAdipose-derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy
Authors
KeywordsAdipose-derived stromal cells
Compressive load
Intervertebral disc
Nucleus pulposus
Issue Date2015
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm
Citation
International Journal of Biological Sciences, 2015, v. 11 n. 2, p. 133-143 How to Cite?
AbstractINTRODUCTION: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. METHODS: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. RESULTS: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). CONCLUSIONS: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3 activity; regulating ECM and modulator genes, suppressing pro-inflammatory factors and preserving CK8. Consequently, the protective impact of ADSCs found in this study provides an essential understanding and expands our knowledge as to the utility of ADSCs therapy for intervertebral disc regeneration.
Persistent Identifierhttp://hdl.handle.net/10722/220177
ISSN
2023 Impact Factor: 8.2
2023 SCImago Journal Rankings: 2.114
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSun, Z-
dc.contributor.authorLuo, B-
dc.contributor.authorLiu, ZH-
dc.contributor.authorSamartzis, D-
dc.contributor.authorLiu, Z-
dc.contributor.authorGao, B-
dc.contributor.authorHuang, L-
dc.contributor.authorLuo, ZJ-
dc.date.accessioned2015-10-16T06:31:39Z-
dc.date.available2015-10-16T06:31:39Z-
dc.date.issued2015-
dc.identifier.citationInternational Journal of Biological Sciences, 2015, v. 11 n. 2, p. 133-143-
dc.identifier.issn1449-2288-
dc.identifier.urihttp://hdl.handle.net/10722/220177-
dc.description.abstractINTRODUCTION: Abnormal biomechanics plays a role in intervertebral disc degeneration. Adipose-derived stromal cells (ADSCs) have been implicated in disc integrity; however, their role in the setting of mechanical stimuli upon the disc's nucleus pulposus (NP) remains unknown. As such, the present study aimed to evaluate the influence of ADSCs upon NP cells in compressive load culture. METHODS: Human NP cells were cultured in compressive load at 3.0MPa for 48 hours with or without ADSCs co-culture (the ratio was 50:50). We used flow cytometry, live/dead staining and scanning electron microscopy (SEM) to evaluate cell death, and determined the expression of specific apoptotic pathways by characterizing the expression of activated caspases-3, -8 and -9. We further used real-time (RT-) PCR and immunostaining to determine the expression of the extracellular matrix (ECM), mediators of matrix degradation (e.g. MMPs, TIMPs and ADAMTSs), pro-inflammatory factors and NP cell phenotype markers. RESULTS: ADSCs inhibited human NP cell apoptosis via suppression of activated caspase-9 and caspase-3. Furthermore, ADSCs protected NP cells from the degradative effects of compressive load by significantly up-regulating the expression of ECM genes (SOX9, COL2A1 and ACAN), tissue inhibitors of metalloproteinases (TIMPs) genes (TIMP-1 and TIMP-2) and cytokeratin 8 (CK8) protein expression. Alternatively, ADSCs showed protective effect by inhibiting compressive load mediated increase of matrix metalloproteinases (MMPs; MMP-3 and MMP-13), disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs; ADAMTS-1 and 5), and pro-inflammatory factors (IL-1beta, IL-6, TGF-beta1 and TNF-alpha). CONCLUSIONS: Our study is the first in vitro study assessing the impact of ADSCs on NP cells in an un-physiological mechanical stimulation culture environment. Our study noted that ADSCs protect compressive load induced NP cell death and degradation by inhibition of activated caspase-9 and -3 activity; regulating ECM and modulator genes, suppressing pro-inflammatory factors and preserving CK8. Consequently, the protective impact of ADSCs found in this study provides an essential understanding and expands our knowledge as to the utility of ADSCs therapy for intervertebral disc regeneration.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.biolsci.org/index.htm-
dc.relation.ispartofInternational Journal of Biological Sciences-
dc.rightsInternational Journal of Biological Sciences. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAdipose-derived stromal cells-
dc.subjectCompressive load-
dc.subjectIntervertebral disc-
dc.subjectNucleus pulposus-
dc.titleAdipose-derived stromal cells protect intervertebral disc cells in compression: implications for stem cell regenerative disc therapy-
dc.typeArticle-
dc.identifier.emailSamartzis, D: dspine@hku.hk-
dc.identifier.authoritySamartzis, D=rp01430-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/ijbs.10598-
dc.identifier.pmid25561896-
dc.identifier.pmcidPMC4279089-
dc.identifier.scopuseid_2-s2.0-84921917633-
dc.identifier.hkuros255797-
dc.identifier.hkuros269615-
dc.identifier.volume11-
dc.identifier.issue2-
dc.identifier.spage133-
dc.identifier.epage143-
dc.identifier.isiWOS:000350408200002-
dc.publisher.placeAustralia-
dc.identifier.issnl1449-2288-

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