Document Detail

Bone Marrow Mesenchymal Stem Cells Slow Intervertebral Disc Degeneration Through the NF-ĸB Pathway.
MedLine Citation:
PMID:  25457469     Owner:  NLM     Status:  Publisher    
BACKGROUND CONTEXT: Previous studies have demonstrated the use of bone marrow mesenchymal stem cells (BMSCs) in tissue-engineering treatments to slow or reverse diseased intervertebral discs. Several approaches have successfully employed the co-culturing of stem cells with disc-native nucleus pulposus cells (NPCs) with evidence of either transformed BMSCs into NP-like cells, increased activity and matrix production by NPCs, or elements of both. The influence of the cytokine TGF-β in the differentiation of BMSCs into NP-like cells and its up-regulation in co-culture to increase matrix production is well established. However, the role of the inflammatory signaling molecule NF-κB in intervertebral disc degeneration is far less clear, although there is some existing evidence suggesting its role in the pathogenesis and progression of disc disease. A limited number of studies in other pathologies have alluded to the antagonistic relationship between both proteins. To date, there is no such investigation of their dynamic role in co-culture of BMSCs and NPCs.
PURPOSE: This study investigates the relationship of the regenerative effects of BMSCs co-cultured with NPCs. The authors hypothesized that as levels of TGF-β increase in the co-culture, the levels of NF- κ B will concomitantly decrease. This would in turn be reflected by an increase in the expression of mRNAs markers of the nucleus pulposus matrix which includes aggrecan, Type II collagen (CII), and SOX-9, as well as increase in cellular proliferation. Study Design/Setting: Co-culture with contact of rabbit NPCs and BMSCs (MSCs).
METHODS: BMSCs were co-cultured with NPCs at a ratio of 1:1, and compared to BMSCS and NPCs controls cultured alone. Cell proliferation was evaluated by CCK-8 from 3 to 9 days. Gene expression of aggrecan, Type II collagen (CII), and SOX-9 was assayed by RT-PCR from 5 to 14 days. Detection of TGF-β l and NF-ĸ B was determined by ELISA, and IHC staining was carried out to evaluate CII synthesis.
RESULTS: After 3 days, cellular proliferation of the co-cultured group exceeded that of controls. Following 11 days, the expression of SOX-9 in the co-cultured group had also exceeded controls. Furthermore, after 14 days aggrecan and CII significantly expression exceeded controls. Immunohistochemical stains of CII in the NPCs control group were positive at each point in time and demonstrated strongest expression at 14 days. Co-culturing BMSCs with NPCs, therefore, seem to have resulted in the promotion of aggrecan, Type II Collagen, and SOX-9 gene expression. Finally, after 11 days TGF-β l content of the co-cultured group significantly exceeded control levels while NF-ĸ B content had significantly lowered.
CONCLUSIONS: Co-culture of BMSCs may be able to delay NPC matrix degeneration potentially through the concomitant upregulation of TGF-β and the downregulation of NF-ĸ B pathway.
Cheng Cao; Jun Zou; Xiaochen Liu; Anna Shapiro; Muhammad Moral; Zongping Luo; Qin Shi; Jiayong Liu; Huilin Yang; Nabil Ebraheim
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-29
Journal Detail:
Title:  The spine journal : official journal of the North American Spine Society     Volume:  -     ISSN:  1878-1632     ISO Abbreviation:  Spine J     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  101130732     Medline TA:  Spine J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 Elsevier Inc. All rights reserved.
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