Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells

Kuroda, Ryosuke; Ishida, Kazunari; Matsumoto, Tomoyuki; Akisue, Toshihiro; Fujioka, Hiroyuki; Mizuno, Kosaku; Ohgushi, Hajime; Wakitani, Shigeyuki; Kurosaka, Masahiro

doi:10.1016/j.joca.2006.08.008

Cited by 371 publications

(276 citation statements)

References 19 publications

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“…In order to harness MSCs for cartilage tissue engineering, analyses of the appropriate three-dimensional microenvironment to stimulate MSCs toward chondrogenesis in vitro und in vivo have been performed extensively, with factors such as TGF-β1, 2, -3, and BMP-2 emerging among the most popular candidates (see also Table 1). This research has led to the first clinical application of autologous bone marrow stromal cells for the repair of full-thickness articular cartilage defects in humans, which resulted in stable fibrocartilage tissue formation at the defect site [93,187]. However, a successful use of MSCs to aid cartilage repair by means of generating a stable hyaline-rich cartilage repair tissue in vivo, likely requires the efficient delivery of factors to stimulate MSCs toward chondrogenesis, and maintenance of an articular cartilage phenotype without ossification, fibrinogenesis, or inflammation [23,80,177].…”

Section: Gene Transfer To Mesenchymal Stem Cellsmentioning

confidence: 99%

Concepts in gene therapy for cartilage repair

Steinert

Nöth

Tuan

2008

Injury

142

119

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SummaryOnce articular cartilage is injured, it has a very limited capacity for self-repair. Although current surgical therapeutic procedures to cartilage repair are clinically useful, they cannot restore a normal articular surface. Current research offers a growing number of bioactive reagents, including proteins and nucleic acids, that may be used to augment different aspects of the repair process. As these agents are difficult to administer effectively, gene transfer approaches are being developed to provide their sustained synthesis at sites of repair.To augment regeneration of articular cartilage, therapeutic genes can be delivered to the synovium, or directly to the cartilage lesion. Gene delivery to the cells of the synovial lining is generally considered more suitable for chondroprotective approaches, based on the expression of antiinflammatory mediators. Gene transfer targeted to cartilage defects can be achieved by either direct vector administration to cells located at or surrounding the defects, or by transplantation of genetically modified chondrogenic cells into the defect. Several studies have shown that exogenous cDNAs encoding growth factors can be delivered locally to sites of cartilage damage, where they are expressed at therapeutically relevant levels. Furthermore, data is beginning to emerge indicating, that efficient delivery and expression of these genes is capable of influencing a repair response toward the synthesis of a more hyaline cartilage repair tissue in vivo. This review presents the current status of gene therapy for cartilage healing and highlights some of the remaining challenges.

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Section: Gene Transfer To Mesenchymal Stem Cellsmentioning

confidence: 99%

Concepts in gene therapy for cartilage repair

Steinert

Nöth

Tuan

2008

Injury

142

119

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show abstract

“…43,44 While the use of MSCs has been shown to improve repair compared with untreated controls, critically normal hyaline cartilage does not regenerate, rather a hyaline-like or fibro-cartilagenous tissue forms. [45][46][47] Chondrogenic predifferentiation of MSCs within collagen gels, leading to improved functionality of the engineered graft prior to implantation, has been shown to improve the outcome in long-term sheep studies, 48 resulting in superior repair compared with undifferentiated MSCs or chondrocytes.…”

Section: Introductionmentioning

confidence: 99%

The Role of Environmental Factors in Regulating the Development of Cartilaginous Grafts Engineered Using Osteoarthritic Human Infrapatellar Fat Pad–Derived Stem Cells

Liu

Buckley

Downey

et al. 2012

Tissue Engineering Part A

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“…To date, MSCs derived from the bone marrow have been the prime site of cell harvesting for cartilage therapy development Kuroda et al, 2007;Wakitani et al, 2007). More recently, interest has also extended to utilising MSCs from other locations, and in the case of knee joint cartilage repair, from non-cartilaginous knee joint tissues.…”

Section: Introductionmentioning

confidence: 99%

Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells

Buckley

Vinardell

Thorpe

et al. 2010

Journal of Biomechanics

106

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Articular cartilage has a poor intrinsic capacity for self repair. The advent of autologous chondrocyte implantation has provided a feasible method to treat cartilage defects.However, the associated drawbacks with the isolation and expansion of chondrocytes from autologous tissue has prompted research into alternative cell sources such as mesenchymal stem cells (MSCs) which have been found to exist in the bone marrow as well as other joint tissues such as the infrapatellar fat pad (IFP), synovium and within the synovial fluid itself. In this work we assessed the chondrogenic potential of IFP derived porcine cells over a six week period in agarose hydrogel culture in terms of mechanical properties, biochemical content and histology. It was found that IFP cells underwent robust chondrogenesis as assessed by glycosaminoglycan (1.47 ± 0.22 % w/w) and collagen (1.44 ± 0.22 % w/w) accumulation after 42 days of culture. The 1Hz dynamic modulus of the engineered tissue at this time-point was 272.8 kPa (± 46.8). The removal of TGF-β3 from culture after 21 days was shown to have a significant effect on both the mechanical properties and biochemical content of IFP constructs after 42 days, with minimal increases occurring from day 21 to day 42 without continued supplementation of TGF-β3. These findings further strengthen the case that the IFP may be a promising cell source for putative cartilage repair strategies.3

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Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells

Abstract: Our findings indicate that the transplantation of autologous bone-marrow stromal cells can promote the repair of large focal articular cartilage defects in young, active patients.

Cited by 371 publications

References 19 publications

Concepts in gene therapy for cartilage repair

Concepts in gene therapy for cartilage repair

The Role of Environmental Factors in Regulating the Development of Cartilaginous Grafts Engineered Using Osteoarthritic Human Infrapatellar Fat Pad–Derived Stem Cells

Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells

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