Commentary & Perspective

Commentary & Perspective on
"Transplantation of Viable Meniscal Allograft: Survivorship Analysis and Clinical Outcome of One Hundred Cases"
by Peter C.M. Verdonk, MD, et al.

Commentary & Perspective by
Scott A. Rodeo, MD*,
Hospital for Special Surgery, New York, NY

The paper by Verdonk et al. presents a thorough review of the clinical outcome of 100 meniscal transplantations in ninety-six patients. I commend the authors for their high rate of follow-up and the careful outcome analysis. Overall, the authors demonstrate that meniscal transplantation can result in improved symptoms in patients with pain and swelling due to early arthrosis. The authors report survival rates of approximately 70% at ten years for both medial and lateral meniscal transplants.

The strengths of this paper are threefold: there is a high rate of follow-up; there is relatively long-term follow-up (mean 7.2 years); and the authors have performed a careful analysis of symptoms and knee function.

A limitation of the paper is that the authors have defined failure by subjective criteria based on questionnaire scores. There is no direct evaluation of the status of the meniscal allograft. Such an evaluation would require either magnetic resonance imaging scan or arthroscopic inspection. Because previous studies have demonstrated that a meniscal transplant may be degenerated and even torn, while the patient may have minimal symptoms, the outcome analysis presented here may miss asymptomatic meniscal failures. The authors do acknowledge this point in their Discussion.

I would suggest that outcome evaluations of reconstructive procedures (such as meniscal transplantation) should include subjective scoring both of symptoms and function as well as direct objective evaluation of the implant. I believe this is an important point, as studies in our institution as well as other studies have shown a relatively high rate of intrinsic degenerative changes in the transplanted meniscal tissue when the evaluation included appropriate magnetic resonance imaging sequences¹. These changes may be seen in patients who are essentially asymptomatic. Although the cases of such patients may not be considered to be clinical failures, it is likely that the transplanted tissue is not providing the expected function in such patients. Furthermore, many meniscal transplants are performed with other concomitant surgical procedures, such as anterior cruciate ligament reconstruction, a cartilage resurfacing procedure such as microfracture, or osteotomy. In such patients, it is difficult to attribute a good result to the meniscal transplant. Thus, objective evaluation of the status of the transplanted tissue is critical.

The authors demonstrated better results with patients who underwent a concomitant valgus-producing proximal tibial osteotomy. Of note, the patients in that group had a greater degree of preoperative degenerative joint disease. Many studies have demonstrated poorer results in patients with more advanced hyaline cartilage degeneration. The finding of better results in this patient group suggests that the good result is likely due, at least in part, to the concomitant osteotomy. This again points out the need for objective evaluation of the transplanted meniscal tissue.

The authors make the important point that meniscal transplantation is contraindicated in the setting of malalignment, and osteotomy should be considered in those patients. However, it is not known if osteotomy truly makes the affected compartment suitable for transplantation in a patient who otherwise would have been contraindicated. The idea that osteotomy and meniscal transplantation can be routinely combined should be viewed with caution because many patients who have undergone osteotomy have serious architectural changes in the joint, and these changes are typically believed to be contraindications to meniscal transplantation¹. For example, there is often some flattening of the femoral condyle, and studies in our institution (as well as studies by other authors) have demonstrated that flattening of the femoral condyle is associated with a higher failure rate of meniscal transplantation. A simple shifting of the mechanical axis to the contralateral compartment with osteotomy does not affect these architectural changes. I do agree that combined osteotomy and meniscal transplantation may be considered in patients who do not have advanced architectural changes in the involved tibiofemoral compartment.

The authors performed their meniscal transplants without attached bone to enhance fixation. Several studies have demonstrated better graft fixation with bone plugs attached to the anterior and posterior horns. On the lateral side, many surgeons will transplant the lateral meniscus with a common bone slot which contains the attachments of the anterior and posterior horns. In-vitro studies demonstrate better restoration of contact mechanics in the joint if the meniscus is transplanted with osseous fixation rather than simple suture fixation². Nonetheless, the authors report good results here with a technique that did not use bone plug fixation, suggesting that they achieved adequate fixation and healing of the transplanted menisci.

In this paper, the authors have transplanted viable meniscal tissue. These grafts were harvested in a sterile manner and then cultured while the donors were screened for transmissible diseases. The rationale for transplanting tissue with viable cells is that these cells may contribute to synthesis of extracellular matrix molecules and to the repair of microscopic damage in the tissue. However, it is not known exactly how long and to what degree the transplanted cells remain viable and continue to function. The authors cite a well-done study by Jackson et al, who used DNA probe analysis in a goat model and found that all donor cells were rapidly replaced by host cells by four weeks following transplantation³. However, the authors have previously presented data suggesting that donor DNA can still be detected in the transplanted tissue more than five years following transplantation⁴. It appears that cellular repopulation of transplanted tissue in humans is a much slower process compared with that seen in existing animal studies. The presence of viable donor cells may render the tissue more immunogenic; however, the authors did not report any clinical evidence of immune rejection. Further studies are necessary to further our understanding of the biology of transplanting viable meniscus.

One of the principle concerns with meniscus transplantation at this time is the degenerative changes which are found to occur in transplanted tissue over time. This has been noted with use of magnetic resonance imaging. These data are derived almost exclusively from series of patients who have received acellular, frozen, meniscal tissue. It is possible that adverse changes in the tissue may not occur with a viable cell population, and thus I would encourage the authors to use high-quality magnetic resonance imaging to assess their meniscal transplants.

It is notable that the authors did not demonstrate an association between the degree of preoperative hyaline cartilage degeneration and the outcome of the meniscal transplant. Other studies have demonstrated higher failure rates in patients with more advanced cartilage degeneration. All patients in this series had some degree of cartilage degeneration, with the average Outerbridge scores preoperatively between two and three in the affected compartments. It is possible that the success of meniscal transplants will be greater in knees with less hyaline cartilage degeneration. The authors did note that higher grades of articular cartilage degeneration at the time of failure were associated with more advanced degenerative changes in the meniscal allograft. This demonstrates a close interrelation between the status and function of the meniscus and the adjacent hyaline cartilage surface. My own experience has been that the failure rate of meniscal transplantation appears to be higher in knees with more advanced degenerative changes, and thus this procedure should generally be carried out in patients who have early hyaline cartilage changes only. Furthermore, meniscal transplantation should only be carried out in knees that show appropriate alignment and the absence of architectural changes on the femoral condyles (flattening of the condyle).

This paper points to the need for a prospective randomized trial with appropriate subjective and objective evaluations of outcome. Meniscal transplantation is an option for that difficult group of patients for whom there are often no other good surgical options. In the group of young and middle-age patients who present with symptoms and signs of excessive joint-loading secondary to meniscal deficiency but who have normal alignment, osteotomy is not an option. A cartilage resurfacing procedure is not indicated because this group usually has only early degenerative cartilage changes. They are not candidates for arthroplasty because of the relatively mild degree of degeneration and because of their desire to lead an active lifestyle. Thus, meniscal transplantation becomes the best (and often the only) option for these patients.

I believe that improvements in meniscal transplantation will be made as we gain additional knowledge about both the biological and biomechanical factors associated with meniscal transplantation. In particular, several areas are in need of further research. We need improved understanding of the effects of mechanical load on remodeling of the transplanted meniscal tissue. This information will provide objective evidence to assist in directing rehabilitation protocols. Improved techniques to maintain cell viability and decrease immunogenicity may allow more widespread use of viable meniscal tissue. Biopsy studies from our laboratory have demonstrated appreciable remodeling of the meniscus in association with cellular repopulation. This result would be expected, since migration of cells into the dense meniscal tissue requires breakdown and remodeling of the extracellular matrix. Perhaps it would be better to transplant tissue with viable cells and thus prevent repopulation with host cells. If the transplanted cells remain viable in the tissue and synthesize appropriate matrix molecules and repair microscopic matrix damage, then the apparent degenerative changes that are often found with magnetic resonance imaging may be delayed or even prevented.

Ultimately, the success of meniscal transplantation may be improved greatly by gene therapy techniques. For example, the cells in the allograft may be transfected with genes for appropriate cytokines that can improve matrix molecule production. Other options may be to increase the expression of genes for tissue inhibitors of metalloproteinase. These molecules inhibit metalloproteinase activity and thus may prevent breakdown of the extracellular matrix. Further understanding of the biology of the transplanted meniscus may allow these possibilities to become reality in the near future.

In summary, I believe that meniscal transplantation remains an effective procedure in carefully selected patients. The current study by Verdonk et al. demonstrates good clinical results with a satisfactory rate of survival at ten years following transplantation. Because this group of patients is difficult to treat and also because of the complexities of meniscal transplantation, improved techniques are needed for meniscal transplantation. Perhaps, in the future, tissue-engineered meniscal tissue or a synthetic meniscal prosthesis will become available, allowing for an "off-the-shelf" option for replacement of the meniscus.

*The author did not receive grants or outside funding in support of his research or preparation of this manuscript. He did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the author is affiliated or associated.

References

1. Noyes FR, Barber-Westin SD, Rankin M. Meniscal transplantation in symptomatic patients less than fifty years old. J Bone Joint Surg Am. 2004;86:1392-404.
2. Paletta GA Jr, Manning T, Snell E, Parker R, Bergfeld J. The effect of allograft meniscal replacement on intraarticular contact area and pressures in the human knee. A biomechanical study. Am J Sports Med. 1997;25:692-8.
3. Jackson DW, Whelan J, Simon TM. Cell survival after transplantation of fresh meniscal allografts. DNA probe analysis in a goat model. Am J Sports Med. 1993;21:540-50.
4. Verdonk P, Almqvist KF, Lootens T, Van Hoofstat D, Van Den Eeckhout E, Verbruggen G, Berdonk R. DNA fingerprinting of fresh viable meniscal allografts transplantated in the human knee [abstract]. Osteoarthritis Cartilage. 2002;10(Supple A):S43-S44.

Copyright © 2005 by the The Journal of Bone and Joint Surgery, Inc.