Document Detail

Effect of cell density on the rate of glycosaminoglycan accumulation by disc and cartilage cells in vitro.
MedLine Citation:
PMID:  17985391     Owner:  NLM     Status:  MEDLINE    
Aggrecan concentration falls markedly during cartilage and disc degeneration with unfortunate biomechanical and physiological consequences. There is thus now an increasing interest in developing biological methods for its replacement. One approach is to stimulate aggrecan and hence glycosaminoglycan (GAG) production by resident cells through growth factor or genetic engineering. Another approach is to implant autologous cells into the cartilage or disc to enhance GAG production. In both instances GAG accumulation depends both on the number of active cells in the cartilage or disc and the rate of aggrecan synthesis per cell. Here we examine how cell density influences the rate of glycosaminoglycan accumulation in a three-dimensional cell culture system. In the results, at cell densities found in vivo (standard condition) in the articular cartilage and the disc nucleus viz. 4 million cells/ml and at 21% oxygen the concentration of GAG in the bead reached 520.9+/-62.4 microg/ml and 649.0+/-40.1 microg/ml, respectively, in 5 days. These concentrations could be increased to 2-4-fold by raising cell density to 25 million cells/ml. However, rates of GAG production per cell decreased by 50-60%. These results showed that rate of accumulation of glycosaminoglycan in this culture system in vitro is slow and is limited both by the rate of production of GAG per cell and by the cell density which can be maintained in a viable state. Although GAG production can be increased somewhat by use of higher cell densities, the consequent fall in concentration of oxygen and other nutrients in the center of three-dimensional constructs slows metabolism and leads to apoptosis and cell death, which again limits the rate that the cells can produce matrix.
Shigeru Kobayashi; Adam Meir; Jill Urban
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of orthopaedic research : official publication of the Orthopaedic Research Society     Volume:  26     ISSN:  1554-527X     ISO Abbreviation:  J. Orthop. Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-12     Completed Date:  2008-04-08     Revised Date:  2011-12-01    
Medline Journal Info:
Nlm Unique ID:  8404726     Medline TA:  J Orthop Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  493-503     Citation Subset:  IM    
Copyright Information:
(c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
Department of Physiology, Anatomy, and Genetics, Oxford University, Oxford, United Kingdom.
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MeSH Terms
Biocompatible Materials
Cartilage, Articular / metabolism*
Cell Count
Cell Culture Techniques
Cell Survival
Cells, Cultured
Glucuronic Acid
Glycosaminoglycans / metabolism*
Hexuronic Acids
Intervertebral Disc / metabolism*
Time Factors
Grant Support
//Arthritis Research UK
Reg. No./Substance:
0/Alginates; 0/Biocompatible Materials; 0/Glycosaminoglycans; 0/Hexuronic Acids; 576-37-4/Glucuronic Acid; 9005-32-7/alginic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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