The potential of human allogeneic juvenile chondrocytes for restoration of articular cartilage.
BACKGROUND
Donor-site morbidity, limited numbers of cells, loss of phenotype during ex vivo expansion, and age-related decline in chondrogenic activity present critical obstacles to the use of autologous chondrocyte implantation for cartilage repair. Chondrocytes from juvenile cadaveric donors may represent an alternative to autologous cells. Hypothesis/


OBJECTIVE
The authors hypothesized that juvenile chondrocyte would show stronger and more stable chondrogenic activity than adult cells in vitro and that juvenile cells pose little risk of immunologic incompatibility in adult hosts.


METHODS
Controlled laboratory study.


METHODS
Cartilage samples were from juvenile (<13 years old) and adult (>13 years old) donors. The chondrogenic activity of freshly isolated human articular chondrocytes and of expanded cells after monolayer culture was measured by proteoglycan assay, gene expression analysis, and histology. Lymphocyte proliferation assays were used to assess immunogenic activity.


RESULTS
Proteoglycan content in neocartilage produced by juvenile chondrocytes was 100-fold higher than in neocartilage produced by adult cells. Collagen type II and type IX mRNA in fresh juvenile chondrocytes were 100- and 700-fold higher, respectively, than in adult chondrocytes. The distributions of collagens II and IX were similar in native juvenile cartilage and in neocartilage made by juvenile cells. Juvenile cells grew significantly faster in monolayer cultures than adult cells (P = .002) and proteoglycan levels produced in agarose culture was significantly higher in juvenile cells than in adult cells after multiple passages (P < .001). Juvenile chondrocytes did not stimulate lymphocyte proliferation.


CONCLUSIONS
These results document a dramatic age-related decline in human chondrocyte chondrogenic potential and show that allogeneic juvenile chondrocytes do not stimulate an immunologic response in vivo.


CONCLUSIONS
Juvenile human chondrocytes have greater potential to restore articular cartilage than adult cells, and may be transplanted without the fear of rejection, suggesting a new allogeneic approach to restoring articular cartilage in older individuals.
Adkisson
H Davis
HD
ISTO Technologies, Inc, St Louis, Missouri, St Louis, MO 63132, USA. hadkisson@istotech.com
Martin
James A
JA
Amendola
Richard L
RL
Milliman
Curt
C
Mauch
Kelsey A
KA
Katwal
Arbindra B
AB
Seyedin
Mitchell
M
Amendola
Annuziato
A
Streeter
Philip R
PR
Buckwalter
Joseph A
JA
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002357:Cartilage Diseases / Q000601:surgery; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000737:chemistry / Q000502:physiology* / Q000637:transplantation*; D024043:Collagen Type II / Q000032:analysis / Q000378:metabolism; D024081:Collagen Type IX / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000032:analysis / Q000378:metabolism; D012038:Regeneration; D055815:Young Adult
D024043:Collagen Type II; D024081:Collagen Type IX; D011509:Proteoglycans