Transplantation of Achilles Tendon Treated With Bone Morphogenetic Protein 7 Promotes Meniscus Regeneration in a Rat Model of Massive Meniscal Defect

Ozeki, Nobutake; Muneta, Takeshi; Koga, Hideyuki; Katagiri, Hiroki; Otabe, Koji; Okuno, Masashi; Tsuji, Kunikazu; Kobayashi, Eiji; Matsumoto, Kenji; Saito, Hirohisa; Saito, T.; Sekiya, Ichiro

doi:10.1002/art.38099

Cited by 48 publications

(46 citation statements)

References 49 publications

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“…The sheep model also does not permit broad immunophenotyping of regenerated tissues owing to a paucity of antibodies and probes. Although we were unable to track cell recruitment in the sheep, host cell recruitment was demonstrated in a 50% rat meniscus resection defect when LacZ + cells in BMP7-treated Achilles tendon allograft were transplanted (33,34), which supports our hypothesis of meniscus regeneration by endogenous cells.…”

Section: Discussionsupporting

confidence: 50%

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

et al. 2014

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Regeneration of complex tissues, such as kidney, liver, and cartilage, continues to be a scientific and translational challenge. Survival of ex vivo cultured, transplanted cells in tissue grafts is among one of the key barriers. Meniscus is a complex tissue consisting of collagen fibers and proteoglycans with gradient phenotypes of fibrocartilage and functions to provide congruence of the knee joint, without which the patient is likely to develop arthritis. Endogenous stem/progenitor cells regenerated the knee meniscus upon spatially released human connective tissue growth factor (CTGF) and transforming growth factor–β3 (TGFβ3) from a three-dimensional (3D)–printed biomaterial, enabling functional knee recovery. Sequentially applied CTGF and TGFβ3 were necessary and sufficient to propel mesenchymal stem/progenitor cells, as a heterogeneous population or as single-cell progenies, into fibrochondrocytes that concurrently synthesized procollagens I and IIα. When released from microchannels of 3D–printed, human meniscus scaffolds, CTGF and TGFβ3 induced endogenous stem/progenitor cells to differentiate and synthesize zone-specific type I and II collagens. We then replaced sheep meniscus with anatomically correct, 3D–printed scaffolds that incorporated spatially delivered CTGF and TGFβ3. Endogenous cells regenerated the meniscus with zone-specific matrix phenotypes: primarily type I collagen in the outer zone, and type II collagen in the inner zone, reminiscent of the native meniscus. Spatiotemporally delivered CTGF and TGFβ3 also restored inhomogeneous mechanical properties in the regenerated sheep meniscus. Survival and directed differentiation of endogenous cells in a tissue defect may have implications in the regeneration of complex (heterogeneous) tissues and organs.

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Section: Discussionsupporting

confidence: 50%

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

et al. 2014

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“…Non-viral vectors provide the potential to expedite the process of translation but their use is constrained by transient, low level expression of the genes they carry. As noted by the work of Ozeki et al (34), described earlier in this review, it may prove possible to achieve the in situ differentiation of progenitor cells using a single application of a recombinant protein, rather than a vector, which would simplify the process even further. It may also be possible using small molecules (37).…”

Section: Discussionmentioning

confidence: 93%

“…Ozeki et al (34) were able to regenerate meniscal tissue in rat knees using transplanted Achilles tendon. BMP-7 was first injected into the tendon to initiate differentiation of multipotent progenitor cells into fibrochondrocytes.…”

Section: Tendon and Ligamentmentioning

confidence: 99%

Native, Living Tissues as Cell Seeded Scaffolds

Evans

2014

Ann Biomed Eng

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Much effort is expended in developing biomimetic scaffolds that provide the micro-architecture of native tissue with appropriate cellular niches. Such scaffolds are often seeded with progenitor cells to generate engineered replacements for diseased or damaged tissues. An alternative approach relies on biology, rather than technology, to provide scaffolds containing progenitor cells in authentic niches. This article describes the use of accessible living tissues containing endogenous progenitor cells in their native, physiological environments. Such tissues also possess scaffolding properties, and can be readily harvested, manipulated and returned to the patient intra-operatively to facilitate repair and regeneration. Our group has explored the in situ genetic manipulation of cells within these tissues before they are reimplanted, although other means of modulation are certainly possible. Examples of suitable donor tissues include marrow, skeletal muscle and fat. In the case of marrow, clotting produces a moldable, autologous fibrin matrix containing endogenous cells; if necessary, exogenous cells can be added prior to clotting. These approaches have been studied experimentally in orthopaedic contexts, particularly for the healing and regeneration of bone and cartilage.

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“…After the patellar tendon was dislocated laterally and the anterior insertional ligament of the medial meniscus was cut, the anterior half of the medial meniscus was resected at the level of the medial collateral ligament. The posterior part of the medial meniscus was left remained, and the wound was closed in layers . Immediately after the skin incision was closed, a 27‐gauge needle was inserted at the center of the triangle formed by the medial side of the patellar ligament, the medial femoral condyle, and the medial tibial condyle, toward the intercondylar space of the femur.…”

Section: Methodsmentioning

confidence: 99%

Meniscus regeneration by syngeneic, minor mismatched, and major mismatched transplantation of synovial mesenchymal stem cells in a rat model

Okuno

Muneta

Koga

et al. 2014

Journal Orthopaedic Research

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ABSTRACT:We compared the effect of syngeneic and allogeneic transplantation of synovial mesenchymal stem cells (MSCs) for meniscus regeneration in a rat model. Synovium was harvested from the knee joints of three strains of rats. The anterior half of the medial meniscus in both knees of F344 rats was removed and 5 million synovial MSCs derived from F344 (syngeneic transplantation), Lewis (minor mismatched transplantation), and ACI (major mismatched transplantation) were injected into the knee of the F344 rats. At 4 weeks, the area of the regenerated meniscus in the F344 group was significantly larger than that in the ACI group. Histological score was significantly better in the F344 and Lewis groups than in the ACI group at 8 weeks. DiI labeled cells could be observed in the knee joint in the F344 group, but were hardly detected in the ACI group at 1 week. The number of macrophages and CD8 T cells at synovium around the meniscus defect was significantly lower in the F344 group than in the ACI group at 1 week. Syngeneic and minor mismatched transplantation of synovial MSCs promoted meniscus regeneration better than major mismatched transplantation in a rat meniscectmized model. The meniscus is a fibrocartilage whose functions are to increase surface contact area, to absorb mechanical loads, and to improve stability across the knee joint. Meniscal injury is one of the most common injuries of the knee joint, primarily due to sports injuries or degenerative conditions. For injured menisci, efforts have been made to preserve the meniscus as much as possible to prevent degenerative arthritis. For meniscal defects after meniscectomy or meniscal degeneration, transplantations of meniscal grafts or artificial menisci have been attempted; however, the invasiveness, durability and safety of the transplant remain controversial.1 Therefore, a novel strategy for meniscus regeneration is required.Mesenchymal stem cells (MSCs), especially those derived from synovium, are an attractive cell source for meniscus regeneration, because synovial MSCs have remarkable proliferation 2 and chondrogenic potential.3-5 We previously reported that intraarticular injection of synovial MSCs promoted meniscal regeneration in a rat model. 6 It was a syngeneic transplantation model; therefore, possible immune reactions seem to be negligible. MSCs have potent anti-inflammatory/immunosuppressive properties.7 This suggests that allogeneic MSCs can be used therapeutically with equal efficacy to autologous MSCs without triggering the donor specific immune responses. However, this is still controversial, and the opposite results were also reported. [8][9][10] In regard to synovial MSCs, the influence of allogeneic transplantation has not been investigated at all. In this study, we compared the effect of syngeneic and allogeneic transplantation of synovial MSCs for meniscus regeneration in a rat model. For allogeneic transplantations, major antigen mismatched and minor antigen mismatched MSCs were also prepared. MATERIALS AND METHODS AnimalsThis study w...

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Transplantation of Achilles Tendon Treated With Bone Morphogenetic Protein 7 Promotes Meniscus Regeneration in a Rat Model of Massive Meniscal Defect

Cited by 48 publications

References 49 publications

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

Protein-releasing polymeric scaffolds induce fibrochondrocytic differentiation of endogenous cells for knee meniscus regeneration in sheep

Native, Living Tissues as Cell Seeded Scaffolds

Meniscus regeneration by syngeneic, minor mismatched, and major mismatched transplantation of synovial mesenchymal stem cells in a rat model

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