The Journal of Bone and Joint Surgery 82:1071 (2000)
© 2000 The Journal of Bone and Joint Surgery, Inc.
Histological Analysis of Human Meniscal Allografts
A Preliminary Report*
Scott A. Rodeo, M.D. ,
Aruna Seneviratne, M.D.,
Katsunori Suzuki, M.D. ,
Kevin Felker, B.S.,
Thomas L. Wickiewicz, M.D. and
Russell F. Warren, M.D.
Investigation performed at the Laboratory for Soft Tissue
Research, The Hospital for Special Surgery, New York, N.Y.
*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: rodeos{at}hss.edu
Department of Orthopaedic Surgery, Oji General Hospital, 3-4-8
Wakakusa-cho, Tomakomai 053-8506, Japan.
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 age-matched controls were examined as
well. All twenty-eight 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 T-cells) 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.
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