Adapted chondrogenic differentiation of human mesenchymal stem cells via controlled release of TGF-β1 from poly(ethylene oxide)-terephtalate/poly(butylene terepthalate) multiblock scaffolds

Rey‐Rico, Ana; Venkatesan, Jagadeesh K.; Sohier, Jérôme; Moroni, Lorenzo; Cucchiarini, Magali; Madry, Henning

doi:10.1002/jbm.a.35181

Cited by 24 publications

(26 citation statements)

References 63 publications

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“…of studiesReferencesCell SourceNo. of studies a ReferencesHuman73[48, 50, 52, 53, 168–236]Bone marrow62[48, 50–53, 164, 168, 170–173, 177–180, 182–185, 187, 188, 192, 195–197, 203, 206–210, 212, 216, 217, 219, 221, 223, 227, 230, 232–235, 237–255]Rabbit17[240–242, 246, 249, 252, 255–265]Adipose36[66, 169, 175, 176, 181, 186, 189, 193, 194, 199, 201, 202, 211, 214, 216, 218–220, 224, 228, 229, 231, 235, 242, 256, 257, 260–269]Bovine5[51, 164, 243, 245, 270]Synovium9[174, 191, 200…”

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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“…Proteoglycans were measured spectrophotometrically by binding to the dimethylmethylene blue dye using chondroitin-6-sulfate to generate a standard curve (n = 6)5152. The DNA contents were determined by the Hoechst 33258 assay535455. All data were normalized to the total protein contents assessed by a BCA assay (Pierce, Limburg, Germany), and to the DNA contents535455.…”

Section: Methodsmentioning

confidence: 99%

“…The DNA contents were determined by the Hoechst 33258 assay535455. All data were normalized to the total protein contents assessed by a BCA assay (Pierce, Limburg, Germany), and to the DNA contents535455. All measurements were performed on a GENios spectrophotometer/fluorometer (Tecan, Crailsheim, Germany).…”

Section: Methodsmentioning

confidence: 99%

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Biomedical-grade, high mannuronic acid content (BioMVM) alginate enhances the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D microenvironment

Rey‐Rico

Klich

Cucchiarini

et al. 2016

Sci Rep

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Alginates are important hydrogels for meniscus tissue engineering as they support the meniscal fibrochondrocyte phenotype and proteoglycan production, the extracellular matrix (ECM) component chiefly responsible for its viscoelastic properties. Here, we systematically evaluated four biomedical- and two nonbiomedical-grade alginates for their capacity to provide the best three-dimensional (3-D) microenvironment and to support proteoglycan synthesis of encapsulated human meniscal fibrochondrocytes in vitro. Biomedical-grade, high mannuronic acid alginate spheres (BioLVM, BioMVM) were the most uniform in size, indicating an effect of the purity of alginate on the shape of the spheres. Interestingly, the purity of alginates did not affect cell viability. Of note, only fibrochondrocytes encapsulated in BioMVM alginate produced and retained significant amounts of proteoglycans. Following transplantation in an explant culture model, the alginate spheres containing fibrochondrocytes remained in close proximity with the meniscal tissue adjacent to the defect. The results reveal a promising role of BioMVM alginate to enhance the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D hydrogel microenvironment. These findings have significant implications for cell-based translational studies aiming at restoring lost meniscal tissue in regions containing high amounts of proteoglycans.

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“…Here, we selected a strategy of spatiotemporal controlled release of TGF-b1 from solid, cell-free scaffolds to study the mechanisms of early chondrogenesis of MSCs that migrate into and repopulate osteochondral defects (21). We have previously demonstrated the suitability of porous scaffolds that are composed of poly(ethylene oxide)-terephtalate/poly(butylene terephthalate) (PEOT/ PBT) to allow for a controlled and sustained TGF-b1 release for at least 21 d in vitro (22). As much of our current understanding of chondrogenesis in cartilage defects is based on studies in small animals, such as mice or rabbits, we chose the large animal model of osteochondral defects in the distal medial femoral condyles in the stifle joints of adult minipigs (23).…”

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Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

et al. 2018

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The continuous presence of TGF-β is critically important to induce effective chondrogenesis. To investigate chondrogenesis in a cartilage defect, we tested the hypothesis that the implantation of TGF-β1-releasing scaffolds improves very early cartilage repair in vivo. Spatiotemporal controlled release of TGF-β1 was achieved from multiblock scaffolds that were implanted in osteochondral defects in the medial femoral condyles of adult minipigs. We observed a sustained presence of TGF-β1 at 4 wk in vivo, which significantly promoted structural aspects of early overall cartilage repair, especially cellularity, cellular morphology, and safranin O staining intensity. Furthermore, early aggrecan and type II collagen production were both increased in specific topographic patterns in cartilaginous repair tissue. Sustained release of TGF-β1 also increased cell numbers and proliferation, staining intensities for the stem cell surface marker, CD105, and number of stromal cell-derived factor-1 (SDF-1) -positive cells within cartilaginous repair tissue. These data identify a mechanism by which TGF-β1 modulates early chondrogenesis by primarily increasing the number of progenitor cells arising from the subchondral bone marrow compartment via the SDF-1/chemokine (CXC motif) receptor 4 pathway, their proliferation, differentiation, and extracellular matrix deposition in specific topographic patterns, highlighting the pivotal role played by TGF-β1 during this crucial phase.-Asen, A.-K., Goebel, L., Rey-Rico, A., Sohier, J., Zurakowski, D., Cucchiarini, M., Madry, H. Sustained spatiotemporal release of TGF-β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns.

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Adapted chondrogenic differentiation of human mesenchymal stem cells via controlled release of TGF-β1 from poly(ethylene oxide)-terephtalate/poly(butylene terepthalate) multiblock scaffolds

Cited by 24 publications

References 63 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

Biomedical-grade, high mannuronic acid content (BioMVM) alginate enhances the proteoglycan production of primary human meniscal fibrochondrocytes in a 3-D microenvironment

Sustained spatiotemporal release of TGF‐β1 confers enhanced very early chondrogenic differentiation during osteochondral repair in specific topographic patterns

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