Histological Analysis of Human Meniscal Allografts

Background: Little is known about the biology of meniscal allograft transplantation in humans. In particular, little information is available about the phenotype of the cells that repopulate the allograft, whether an immune response is elicited against the graft, and whether the repopulating cells synthesize normal extracellular matrix components. Methods: A small biopsy specimen of the meniscal allograft (twenty-eight menisci in twenty-five patients) and the adjacent synovial membrane (sixteen patients) was harvested during follow-up arthroscopy in patients who had undergone meniscal allograft transplantation at a mean of sixteen months earlier. Seventeen patients had undergone concomitant reconstruction of the anterior cruciate ligament with an allograft. Normal menisci (unimplanted allografts) and synovial specimens from agematched controls were examined as well. All twentyeight meniscal allografts were examined histologically. Immunohistochemical analysis was carried out on ten menisci and nine synovial specimens with use of monoclonal antibodies to class-I and class-II major histocompatibility complex antigens, CD-8, CD-11b, and CD-19 epitopes, as well as other epitopes, to demonstrate immunogenic macromolecules, cytotoxic T-lymphocytes, activated macrophages, and B-lymphocytes. Results: Most of the specimens demonstrated incomplete repopulation with viable cells. The repopulating cells stained positively with phenotype markers for both synovial cells and fibroblasts. Polarized light microscopy demonstrated evidence of active remodeling of the matrix. The cells in frozen, unimplanted menisci stained positively for class-I and class-II human leukocyte antigens, indicating immunogenicity at the time of transplantation. Overall, nine of twelve specimens contained immunoreactive cells (B-lymphocytes or cytotoxic Tcells) in the meniscus or synovial tissue. However, only a small number of these cells was present. There was no evidence of frank immunological rejection. The clinical outcome (success or failure of the transplant) was not related to the overall histological score or to the presence of an immune response in the meniscal or synovial biopsy specimen. Conclusions: Human meniscal allograft transplants are repopulated with cells that appear to be derived from the synovial membrane; these cells appear to actively remodel the matrix. Although there is histological evidence of an immune response directed against the transplant, this response does not appear to affect the clinical outcome. The presence of histocompatibility antigens on the meniscal surface at the time of transplantation (even after freezing) indicates the potential for an immune response against the transplant. Clinical Relevance: Despite the absence of frank immunological rejection, a subtle immune reaction may affect the healing, incorporation, and revascularization of the graft. It is possible that the structural remodeling associated with cellular repopulation may render the meniscus more susceptible to injury. Both clinical and experimental investigations have clearly demonstrated the detrimental effects of meniscectomy. These findings have provided the impetus for meniscal allograft transplantation in meniscus-deficient knees. The current indications for such transplantation include meniscal deficiency in patients with symptoms such as pain or swelling associated with early osteoarthritis (Outerbridge grades II and III) in a stable and normally aligned knee. Currently, only limited information is available regarding the clinical outcomes of this procedure and little is known about the biology of meniscal allograft transplantation in humans. The longterm function of a meniscal allograft transplant requires the presence of viable cells with the ability to synthesize extracellular matrix molecules. However, little is known about the phenotype of the cells that repopulate the allograft, whether an immune response is elicited against the allograft, and whether normal matrix components are synthesized by the transplanted meniscus. Jackson et al. used DNA probe analysis following fresh meniscal allograft transplantation in a goat model to demonstrate that, within one week, the donor cells in the allograft are replaced by host cells. By four weeks, no donor cells remained. Arnoczky et al. examined meniscal allograft transplants in a dog model and reported that transplanted deep-frozen menisci were repopulated with cells that appeared to originate from the adjacent sy*No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. No funds were received in support of this study. †Laboratory for Soft Tissue Research, The Hospital for Special Surgery, 535 East 70th Street, New York, N.Y. 10021. E-mail address for S. A. Rodeo: [email protected]. ‡Department of Orthopaedic Surgery, Oji General Hospital, 3-4-8 Wakakusa-cho, Tomakomai 053-8506, Japan. Copyright © 2000 by The Journal of Bone and Joint Surgery, Incorporated