Synergistic Effects of FGF-18 and TGF-<i>β</i>3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture

Huang, Liangjie; Yi, Long; Zhang, Chunli; He, Ying; Zhou, Liangliang; Liu, Yan; Qian, Long; Hou, Shuxun; Weng, Tujun

doi:10.1155/2018/7139485

Cited by 22 publications

(15 citation statements)

References 29 publications

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“…ACAN, COMP, COL2 and PRG4). Huang et al described the upregulation of ACAN, COMP and PRG4 by FGF-18 on human adipose-derived stem cells, suggesting that a higher concentration of 100 ng/mL was more effective than a lower one (10 ng/mL) [59] . Although working on a different set of cells (i.e.…”

Section: Discussionmentioning

confidence: 99%

Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

et al. 2020

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Current treatments for cartilage lesions are often associated with fibrocartilage formation and donor site morbidity. Mechanical and biochemical stimuli play an important role in hyaline cartilage formation. Biocompatible scaffolds capable of transducing mechanical loads and delivering bioactive instructive factors may better support cartilage regeneration. In this study we aimed to test the interplay between mechanical and FGF-18 mediated biochemical signals on the proliferation and differentiation of primary bovine articular chondrocytes embedded in a chondro-conductive Fibrin-Hyaluronan (FB/HA) based hydrogel. Chondrocytes seeded in a Fibrin-HA hydrogel, with or without a chondro-inductive, FGFR3 selective FGF18 variant (FGF-18v) were loaded into a joint-mimicking bioreactor applying controlled, multi-axial movements, simulating the natural movements of articular joints. Samples were evaluated for DNA content, sulphated glycosaminoglycan (sGAG) accumulation, key chondrogenic gene expression markers and histology. Under moderate loading, samples produced particularly significant amounts of sGAG/DNA compared to unloaded controls. Interestingly there was no significant effect of FGF-18v on cartilage gene expression at rest. Following moderate multi-axial loading, FGF-18v upregulated the expression of Aggrecan (ACAN), Cartilage Oligomeric Matrix Protein (COMP), type II collagen (COL2) and Lubricin (PRG4). Moreover, the combination of load and FGF-18v, significantly downregulated Matrix Metalloproteinase-9 (MMP-9) and Matrix Metaloproteinase-13 (MMP-13), two of the most important factors contributing to joint destruction in OA. Biomimetic mechanical signals and FGF-18 may work in concert to support hyaline cartilage regeneration and repair. Statement of significance Articular cartilage has very limited repair potential and focal cartilage lesions constitute a challenge for current standard clinical procedures. The aim of the present research was to explore novel procedures and constructs, based on biomaterials and biomechanical algorithms that can better mimic joints mechanical and biochemical stimulation to promote regeneration of damaged cartilage. Using a hydrogel-based platform for chondrocyte 3D culture revealed a synergy between mechanical forces and growth factors. Exploring the mechanisms underlying this mechano-biochemical interplay may enhance our understanding of cartilage remodeling and the development of new strategies for cartilage repair and regeneration.

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Section: Discussionmentioning

confidence: 99%

Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

et al. 2020

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“…It is worth noting that protocols similar to this study induced chondrogenesis in hADSC only in combination with TGF-β3 and/or other growth factors (e.g. FGF-18, IGF-1 BMP-6) [ 45 – 48 ]. This BM side preferential chondrogenic differentiation of the hADSCs may again be attributed to the composition of this tissue layer [e.g.…”

Section: Discussionmentioning

confidence: 99%

Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: a comparative study between a collagen scaffold and two xenografts

et al. 2020

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Background Stem cell therapies represent a promising tool in regenerative medicine. Considering the drawbacks of direct stem cell injections (e.g. poor cell localisation), extracellular matrix-based biomaterials (e.g. scaffolds and tissue grafts), due to their compositional biofunctionality and cytocompatibility, are under investigation as potential stem cell carriers. Methods The present study assessed the potential of three commercially available extracellular matrix-based biomaterials [a collagen/glycosaminoglycan scaffold (Integra™ Matrix Wound Dressing), a decellularised porcine peritoneum (XenoMEM™) and a porcine urinary bladder (MatriStem™)] as human adipose-derived stem cell delivery vehicles. Results Both tissue grafts induced significantly (p < 0.01) higher human adipose-derived stem cell proliferation in vitro over the collagen scaffold, especially when the cells were seeded on the basement membrane side. Human adipose-derived stem cell phenotype and trilineage differentiation potential was preserved in all biomaterials. In a splinted wound healing nude mouse model, in comparison to sham, biomaterials alone and cells alone groups, all biomaterials seeded with human adipose-derived stem cells showed a moderate improvement of wound closure, a significantly (p < 0.05) lower wound gap and scar index and a significantly (p < 0.05) higher proportion of mature collagen deposition and angiogenesis (the highest, p < 0.01, was observed for the cell loaded at the basement membrane XenoMEM™ group). All cell-loaded biomaterial groups retained more cells at the implantation side than the direct injection group, even though they were loaded with half of the cells than the cell injection group. Conclusions This study further advocates the use of extracellular matrix-based biomaterials (in particular porcine peritoneum) as human adipose-derived stem cell delivery vehicles. Graphical abstract Comparative analysis of a collagen scaffold (Integra™ Matrix Wound Dressing) and two tissue grafts [decellularised porcine peritoneum (XenoMEM™) and porcine urinary bladder (MatriStem™)] as human adipose-derived stem cells carriers

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“…53 Additionally, a combination of scaffolds and bioactive agents such as platelet-rich plasma or growth factors may also be considered. 54-56 Similar considerations will also be relevant in an older patient population.…”

Section: Discussionmentioning

confidence: 99%

Quality of Cartilage Repair from Marrow Stimulation Correlates with Cell Number, Clonogenic, Chondrogenic, and Matrix Production Potential of Underlying Bone Marrow Stromal Cells in a Rabbit Model

et al. 2018

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Objective Previous studies have shown that intrinsic behavior of subchondral bone marrow stem cells (BMSCs) is influenced by donors and locations. To understand the variability in cartilage repair outcomes following bone marrow stimulation, we tested the hypothesis that in vivo cartilage repair correlates with in vitro biological properties of BMSCs using a rabbit model. Methods Full-thickness cartilage defects were created in the trochlea and condyle in one knee of skeletally mature New Zealand White rabbits ( n = 8) followed by microdrilling. Three-week repair tissues were analyzed by macroscopic International Cartilage Repair Society (ICRS) scores, O’Driscoll histological scores, and Safranin-O (Saf-O) and type-II collagen (Coll-II) % stain. BMSCs isolated from contralateral knees were assessed for cell yield, surface marker expression, CFU-f, %Saf-O, and %Coll-II in pellet culture followed by correlation analyses with the above cartilage repair responses. Results In vivo cartilage repair scores showed strong, positive correlation with cell number, clonogenic, chondrogenic, and matrix production (Coll-II, GAG) potential of in vitro TGF-βIII stimulated BMSC cultures. Trochlear repair showed clear evidence of donor dependency and strong correlation was observed for interdonor variation in repair and the above in vitro properties of trochlear BMSCs. Correlation analyses indicated that donor- and location-dependent variability observed in cartilage repair can be attributed to variation in the properties of BMSCs in underlying subchondral bone. Conclusion Variation in cell number, clonogenic, chondrogenic, and matrix production potential of BMSCs correlated with repair response observed in vivo and appear to be responsible for interanimal variability as well as location-dependent repair.

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Synergistic Effects of FGF-18 and TGF-β3 on the Chondrogenesis of Human Adipose-Derived Mesenchymal Stem Cells in the Pellet Culture

Cited by 22 publications

References 29 publications

Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

Extracellular matrix-based biomaterials as adipose-derived stem cell delivery vehicles in wound healing: a comparative study between a collagen scaffold and two xenografts

Quality of Cartilage Repair from Marrow Stimulation Correlates with Cell Number, Clonogenic, Chondrogenic, and Matrix Production Potential of Underlying Bone Marrow Stromal Cells in a Rabbit Model

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