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Home / Equine Research Bank / BMC Musculoskelet Disord / Immunologic testing of xeno-derived osteochondral grafts usi...
BMC musculoskeletal disorders2005; 6; 36; doi: 10.1186/1471-2474-6-36

Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors.

Abstract: 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.
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Publication Date: 2005-06-29 PubMed ID: 15987525PubMed Central: PMC1184085DOI: 10.1186/1471-2474-6-36Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study investigates the immune response in humans to osteochondral grafts from different animals that have been partially or fully treated with a process called photooxidation.

Background

  • The research addresses the problem of treating osteoarthritis, a degenerative joint disease. It suggests that osteochondral grafts—tissue transplants of bone and cartilage—might help restore damaged joints.
  • These grafts can be autologous (from the patient’s own body) or allogenic (from a donor of the same species). A third and more complicated approach involves using xeno-derived grafts (from a different species).
  • The goal of this study is to assess the human immune response to xeno-derived grafts from various animals that have been treated by photooxidation, a chemical process thought to reduce their recognition as foreign by the immune system.

Methods

  • The research used osteochondral samples from bovine, porcine, ovine and equine sources that had been subjected to different levels of photooxidation.
  • The researchers attempted to gauge the immune response by measuring production levels of certain immunological markers—IL-1, IL-4, IL-6, IL-10, IL-12, and TNF-alpha—in response to these samples. ELISPOT assays, a type of immune assay, were utilized for this purpose.

Results

  • There was a strong production of IL-1, IL-6, IL-10 and TNF-alpha in reaction to untreated bovine, porcine and equine specimens. This suggests that these samples are detected as foreign by the immune system.
  • On the other hand, there was no induction of IL-4 or IL-12, signalling an absence of Th1 and Th2 immunity, respectively.
  • The processed or photooxidized samples, however, did not induce significant activation of the innate immune system. This was observed after an initial cleaning in increasing strengths of ethanol, indicating that the immunogenic properties of these samples were greatly reduced.

Conclusions

  • The study concludes that photooxidized bovine, porcine or equine samples could potentially be used as osteochondral grafts with a reduced likelihood of immune rejection.
  • The results also suggest that while the initial processing step is good at reducing the immune response, photooxidation is necessary to retain the structure and mechanical integrity of the cartilage for immediate joint resurfacing.

Cite This Article

APA
Hetherington VJ, Kawalec JS, Dockery DS, Targoni OS, Lehmann PV, Nadler D. (2005). Immunologic testing of xeno-derived osteochondral grafts using peripheral blood mononuclear cells from healthy human donors. BMC Musculoskelet Disord, 6, 36. https://doi.org/10.1186/1471-2474-6-36

Publication

BMC musculoskeletal disorders
ISSN: 1471-2474
NlmUniqueID: 100968565
Country: England
Language: English
Volume: 6
Pages: 36

Researcher Affiliations

Hetherington, Vincent J
  • Ohio College of Podiatric Medicine, 10515 Carnegie Avenue, Cleveland 44106, USA. vjh@ocpm.edu
Kawalec, Jill S
    Dockery, Douglas S
      Targoni, Oleg S
        Lehmann, Paul V
          Nadler, Daniel

            MeSH Terms

            • Adult
            • Aged
            • Animals
            • Bone Transplantation / immunology
            • Bone and Bones / radiation effects
            • Cartilage / radiation effects
            • Cartilage / transplantation
            • Cattle
            • Cytokines / biosynthesis
            • Enzyme-Linked Immunosorbent Assay
            • Female
            • Horses
            • Humans
            • Immunologic Tests
            • Light
            • Male
            • Middle Aged
            • Monocytes / immunology
            • Monocytes / metabolism
            • Oxidation-Reduction
            • Sheep
            • Swine
            • Transplantation, Heterologous / immunology

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            Citations

            This article has been cited 2 times.
            1. Kuerten S, Batoulis H, Recks MS, Karacsony E, Zhang W, Subbramanian RA, Lehmann PV. Resting of Cryopreserved PBMC Does Not Generally Benefit the Performance of Antigen-Specific T Cell ELISPOT Assays. Cells 2012 Jul 30;1(3):409-27.
              doi: 10.3390/cells1030409pubmed: 24710483google scholar: lookup
            2. Kawalec-Carroll JS, Hetherington VJ, Dockery DS, Shive C, Targoni OS, Lehmann PV, Nadler D, Prins D. Immunogenicity of unprocessed and photooxidized bovine and human osteochondral grafts in collagen-sensitive mice. BMC Musculoskelet Disord 2006 Mar 17;7:32.
              doi: 10.1186/1471-2474-7-32pubmed: 16545115google scholar: lookup
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