Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors.
BACKGROUND
One means of treating osteoarthritis is with autologous or allogeneic osteochondral grafts. The purpose of this study was to evaluate the innate immunological response in humans toward xeno-derived osteochondral grafts that have been partially or entirely treated by the photooxidation process.


METHODS
The antigens tested included bovine, porcine, ovine and equine osteochondral samples that have been treated in successive steps of photooxidation. ELISPOT assays were used to evaluate the production of IL-1, IL-4, IL-6, IL-10, IL-12 and TNF-alpha by human monocytes in response to the antigens.


RESULTS
Results indicated vigorous production of IL-1, IL-6, IL-10 and TNF-alpha in response to untreated bovine, porcine and equine specimens. This indicates that these samples are perceived as foreign, or stimulatory, by the human monocytes. There was no induction of IL-4 or IL-12, which is required for Th2 and Th1 immunity, respectively. In contrast, the processed bovine, porcine and equine samples did not induce significant activation of cells of the innate immune system. This occurred after the first step in processing (after cleaning in increasing strengths of ethanol). This suggests that the processing steps dramatically, if not completely, negated the immunostimulatory properties of the test sample. The results for the ovine samples indicate a reverse response.


CONCLUSIONS
The findings of the study suggest that photooxidized bovine, porcine or equine samples have the potential to be used as an osteochondral graft. Although the first step in processing reduced the immunological response, photooxidation is still necessary to retain the structure and mechanical integrity of the cartilage, which would allow for immediate joint resurfacing.
Hetherington
Vincent J
VJ
Ohio College of Podiatric Medicine, 10515 Carnegie Avenue, Cleveland 44106, USA. vjh@ocpm.edu
Kawalec
Jill S
JS
Dockery
Douglas S
DS
Targoni
Oleg S
OS
Lehmann
Paul V
PV
Nadler
Daniel
D
D000328:Adult; D000368:Aged; D000818:Animals; D016025:Bone Transplantation / Q000276:immunology*; D001842:Bone and Bones / Q000528:radiation effects; D002356:Cartilage / Q000528:radiation effects / Q000637:transplantation*; D002417:Cattle; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006736:Horses; D006801:Humans; D007159:Immunologic Tests; D008027:Light; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010084:Oxidation-Reduction; D012756:Sheep; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology*
D016207:Cytokines