Ex vivo cartilage defect model for the evaluation of cartilage regeneration using mesenchymal stem cells

Iwai, Ryosuke; Fujiwara, Masashi; Wakitani, Shigeyuki; Takagi, Mutsumi

doi:10.1016/j.jbiosc.2010.11.001

Cited by 16 publications

(12 citation statements)

References 20 publications

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“…Fifteen studies [49, 65, 72, 75, 81, 86, 89–97] used a mixture of solutions prepared from hyaluronic acid [65, 92, 94–97], phosphate buffer solution [91], plasma [75], basal medium with chondrogenesis [89], collagen acid [93], sodium alginate [86] or a growth factor medium [90]. Two studies used MSCs only [49, 72].…”

Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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BackgroundThe management of articular cartilage defects presents many clinical challenges due to its avascular, aneural and alymphatic nature. Bone marrow stimulation techniques, such as microfracture, are the most frequently used method in clinical practice however the resulting mixed fibrocartilage tissue which is inferior to native hyaline cartilage. Other methods have shown promise but are far from perfect. There is an unmet need and growing interest in regenerative medicine and tissue engineering to improve the outcome for patients requiring cartilage repair. Many published reviews on cartilage repair only list human clinical trials, underestimating the wealth of basic sciences and animal studies that are precursors to future research. We therefore set out to perform a systematic review of the literature to assess the translation of stem cell therapy to explore what research had been carried out at each of the stages of translation from bench-top (in vitro), animal (pre-clinical) and human studies (clinical) and assemble an evidence-based cascade for the responsible introduction of stem cell therapy for cartilage defects.Main body of abstractThis review was conducted in accordance to PRISMA guidelines using CINHAL, MEDLINE, EMBASE, Scopus and Web of Knowledge databases from 1st January 1900 to 30th June 2015. In total, there were 2880 studies identified of which 252 studies were included for analysis (100 articles for in vitro studies, 111 studies for animal studies; and 31 studies for human studies). There was a huge variance in cell source in pre-clinical studies both of terms of animal used, location of harvest (fat, marrow, blood or synovium) and allogeneicity. The use of scaffolds, growth factors, number of cell passages and number of cells used was hugely heterogeneous.Short conclusionsThis review offers a comprehensive assessment of the evidence behind the translation of basic science to the clinical practice of cartilage repair. It has revealed a lack of connectivity between the in vitro, pre-clinical and human data and a patchwork quilt of synergistic evidence. Drivers for progress in this space are largely driven by patient demand, surgeon inquisition and a regulatory framework that is learning at the same pace as new developments take place.

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Section: Resultsmentioning

confidence: 99%

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

et al. 2017

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“…In vivo, the crosstalk between the tissues is restricted to the bone cartilage interface. Factors secreted by osteoblasts isolated from sclerotic bone, but also mononucleated cells that are present in the bone marrow, have been shown to influence chondrocyte metabolism indicated by a reduction of cartilage matrix synthesis in a co-culture model (Sanchez et al, 2005a,b;Iwai et al, 2011). Therefore, we thought that if the direct communication of all factors released from the subchondral bone, including the bone marrow, with the cartilage of osteochondral explants can be restricted to crosstalk via the cartilage bone interface, cartilage matrix composition may be maintained.…”

Section: Isolation Of Osteochondral Biopsiesmentioning

confidence: 99%

Ex vivo culture platform for assessment of cartilage repair treatment strategies

Schwab

Meeuwsen

Ehlicke

et al. 2017

ALTEX

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SummaryThere is a great need for valuable ex vivo models that allow for assessment of cartilage repair strategies to reduce the high number of animal experiments. In this paper we present three studies with our novel ex vivo osteochondral culture platform. It consists of two separated media compartments for cartilage and bone, which better represents the in vivo situation and enables supply of factors specific to the different needs of bone and cartilage. We investigated whether separation of the cartilage and bone compartments and/or culture media results in the maintenance of viability, structural and functional properties of cartilage tissue. Next, we evaluated for how long we can preserve cartilage matrix stability of osteochondral explants during long-term culture over 84 days. Finally, we determined the optimal defect size that does not show spontaneous self-healing in this culture system. It was demonstrated that separated compartments for cartilage and bone in combination with tissue-specific medium allow for long-term culture of osteochondral explants while maintaining cartilage viability, matrix tissue content, structure and mechanical properties for at least 56 days. Furthermore, we could create critical size cartilage defects of different sizes in the model. The osteochondral model represents a valuable preclinical ex vivo tool for studying clinically relevant cartilage therapies, such as cartilage biomaterials, for their regenerative potential, for evaluation of drug and cell therapies, or to study mechanisms of cartilage regeneration. It will undoubtedly reduce the number of animals needed for in vivo testing.

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“…It is worth mentioning that cartilage regeneration in osteochondral and chondral defects with the use of MSCs transfected with the TGF-β-gene was more effective in contrast to non-transfected MSCs. This phenomenon might be caused by diffusion of TGF-β3 molecules form the transfected cells to the medium [70]. Swine bone marrow-derived mesenchymal stem cells were successfully differentiated into chondrocytes, and then were seeded onto a three dimensional PGA-derived scaffold to construct cartilage.…”

Section: Scale-up Mesenchymal Stem Cell Culturementioning

confidence: 99%

Induced Pluripotent and Mesenchymal Stem Cells as a Promising Tool for Articular Cartilage Regeneration

Trzeciak¹,

Augustyniak²,

Richter³

et al. 2014

J Cell Sci Ther

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The application of stem cells in regenerative medicine has recently become a rapidly growing field, holding promise for combating a number of orthopedic disorders including osteodegenerative ones (osteoporosis and osteoarthritis). Although the differentiation of stem cells into chondrocytes is now intensively investigated on a laboratory scale, implementing the laboratory protocols in clinical practice requires a scale-up culture. In order to apply this technique many aspects of stem cell bioprocessing such as optimal culture conditions for anchoragedependent or anchorage-independent cells and the type of culture must be taken into account. The presence of microcarriers and/or scaffolds for adherent cells is essential, since they provide a three-dimensional microenvironment indispensable for cell growth. For treatment of osteoarthritis, induced pluripotent stem cells and mesenchymal stem cells seem to be the best choice. Although, the scale-up culture using stem cells has been intensively investigated on a laboratory scale, the scale-up culture for clinical application still requires further technical improvements.In this review stem cell bioprocessing including the use of biomaterials, bioreactors, and factors affecting this process, as well as scale-up culture of induced Pluripotent and mesenchymal stem cells were presented and discussed.

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Ex vivo cartilage defect model for the evaluation of cartilage regeneration using mesenchymal stem cells

Cited by 16 publications

References 20 publications

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review

Ex vivo culture platform for assessment of cartilage repair treatment strategies

Induced Pluripotent and Mesenchymal Stem Cells as a Promising Tool for Articular Cartilage Regeneration

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