PMID- 24258526 OWN - NLM STAT- MEDLINE DCOM- 20141124 LR - 20211021 IS - 1432-0932 (Electronic) IS - 0940-6719 (Print) IS - 0940-6719 (Linking) VI - 23 IP - 3 DP - 2014 Mar TI - Using notochordal cells of developmental origin to stimulate nucleus pulposus cells and bone marrow stromal cells for intervertebral disc regeneration. PG - 679-88 LID - 10.1007/s00586-013-3107-8 [doi] AB - PURPOSE: Bone marrow stromal cells (BMSCs) have been proposed to complement the declining population of nucleus pulposus cells (NPCs) found in a degenerative intervertebral disc. Although able to stop degeneration, they could not produce enough matrix to restore a healthy state. Looking at development, when a large amount of matrix is produced, the disc also contains notochordal cells (NCs), potential progenitors or regulators of NPCs. The aim of the study was, therefore, to combine NCs to a BMSC/NPC mix and evaluate their effects on cell phenotype and matrix production, in long-term culture. METHODS: In a 3D hydrogel, NCs were co-cultured in different ratios with BMSCs and/or NPCs. Matrix production, cell morphology, and gene expression of disc markers were assessed after 4 weeks of culture. RESULTS: At day 28, BMSCs/NPCs highly expressed disc matrix markers (type II collagen and aggrecan) and produced disc matrix up to 30 % of values obtained for the positive control (BMSCs under TGFbeta stimulation). The addition of NCs only slightly up-regulated marker expression (6-12x increase); an up-regulation not reflected at the matrix level. During the 4 weeks of culture, however, the NC phenotype changed drastically (morphology, disc marker expression). CONCLUSION: In contrast to previously reported short-term studies, long-term co-cultures with NCs had no substantial effects on BMSCs and NPCs, most likely due to the loss of the NC native phenotype during culture. It, therefore, appears critical to maintain this specific phenotype for a long-term effect of the NCs. FAU - Potier, Esther AU - Potier E AD - Orthopaedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, GEM-Z 4.103, P.O. Box 513, 5600 MB, Eindhoven, The Netherlands, e.potier@tue.nl. FAU - Ito, Keita AU - Ito K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131121 PL - Germany TA - Eur Spine J JT - European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society JID - 9301980 RN - 0 (Aggrecans) RN - 0 (Collagen Type II) SB - IM MH - Aggrecans/metabolism MH - Animals MH - Cattle MH - Coculture Techniques MH - Collagen Type II/metabolism MH - Gene Expression MH - Intervertebral Disc/*metabolism MH - Intervertebral Disc Degeneration/*metabolism/pathology MH - Mesenchymal Stem Cells/*cytology MH - Notochord/*cytology MH - Regeneration MH - Swine PMC - PMC3940810 EDAT- 2013/11/22 06:00 MHDA- 2014/12/15 06:00 PMCR- 2015/03/01 CRDT- 2013/11/22 06:00 PHST- 2013/05/01 00:00 [received] PHST- 2013/11/07 00:00 [accepted] PHST- 2013/11/07 00:00 [revised] PHST- 2013/11/22 06:00 [entrez] PHST- 2013/11/22 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2015/03/01 00:00 [pmc-release] AID - 3107 [pii] AID - 10.1007/s00586-013-3107-8 [doi] PST - ppublish SO - Eur Spine J. 2014 Mar;23(3):679-88. doi: 10.1007/s00586-013-3107-8. Epub 2013 Nov 21.