Induction of Osteogenic Differentiation in Human Mesenchymal Stem Cells by Crosstalk with Osteoblasts

Glueck, Martina; Gardner, Oliver F. W.; Czekanska, Ewa M.; Alini, Mauro; Stoddart, Martin J.; Salzmann, Gian M.; Schmal, Hagen

doi:10.1089/biores.2015.0002

Cited by 30 publications

(22 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…SOX9/RUNX2 ratio, chondrogenesis‐conducive aggregate culture, and osteogenesis inductive P21‐RUNX2‐8R can likely promote osteoclast formation needed for osteochondral differentiation. Similar gene expression profile was observed in the works of Schagemann et al and Glueck et al, where TGFβ (present in chondrogenesis medium) enhances chondrocyte differentiation, osteoblast maturation, and osteoclast maturation .…”

Section: Resultssupporting

confidence: 87%

Osteogenic Programming of Human Mesenchymal Stem Cells with Highly Efficient Intracellular Delivery of RUNX2

Thiagarajan

Abu-Awwad

Dixon

2017

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Mesenchymal stem cells (MSCs) are being exploited in regenerative medicine due to their tri‐lineage differentiation and immunomodulation activity. Currently, there are two major challenges when directing the differentiation of MSCs for therapeutic applications. First, chemical and growth factor strategies to direct osteogenesis in vivo lack specificity for targeted delivery with desired effects. Second, MSC differentiation by gene therapy is difficult as transfection with existing approaches is clinically impractical (viral transfection) or have low efficacy (lipid‐mediated transfection). These challenges can be avoided by directly delivering nonvirally derived recombinant protein transcription factors with the glycosaminoglycan‐binding enhanced transduction (GET) delivery system (P21 and 8R peptides). We used the osteogenic master regulator, RUNX2 as a programming factor due to its stage‐specific role in osteochondral differentiation pathways. Herein, we engineered GET‐fusion proteins and compared sequential osteogenic changes in MSCs, induced by exposure to GET fusion proteins or conventional stimulation methods (dexamethasone and Bone morphogenetic protein 2). By assessing loss of stem cell‐surface markers, upregulation of osteogenic genes and matrix mineralization, we demonstrate that GET‐RUNX2 efficiently transduces MSCs and triggers osteogenesis by enhancing target gene expression directly. The high transduction efficiency of GET system holds great promise for stem cell therapies by allowing reproducible transcriptional control in stem cells, potentially bypassing problems observed with high‐concentration growth‐factor or pleiotropic steroid therapies. Stem Cells Translational Medicine 2017;6:2146–2159

show abstract

Section: Resultssupporting

confidence: 87%

Osteogenic Programming of Human Mesenchymal Stem Cells with Highly Efficient Intracellular Delivery of RUNX2

Thiagarajan

Abu-Awwad

Dixon

2017

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…Β-glycerophosphate which is an integral component of osteogenic differentiation media to provide a phosphate source for the mineralizing osteoblasts, is regarded as hypertrophy promoting reagent for chondrocytes [ 27 ]. The main component of chondrogenic differentiation medium, TGF-β, was shown to cause a downregulation of ALP expression [ 28 ], which was also found in our study for MSC seeded in scaffolds from mineralized salmon collagen ( Figure 4 ). Based on these results we propose an osteochondral medium containing a reduced amount of TGF-β (5 ng/mL), no FCS, high glucose content, bovine serum albumin, as well as the factors stimulating both osteogenic and chondrogenic differentiation: dexamethasone and ascorbic acid-2-phosphate.…”

Section: Discussionsupporting

confidence: 83%

Biphasic Scaffolds from Marine Collagens for Regeneration of Osteochondral Defects

2018

View full text Add to dashboard Cite

Background: Collagens of marine origin are applied increasingly as alternatives to mammalian collagens in tissue engineering. The aim of the present study was to develop a biphasic scaffold from exclusively marine collagens supporting both osteogenic and chondrogenic differentiation and to find a suitable setup for in vitro chondrogenic and osteogenic differentiation of human mesenchymal stroma cells (hMSC). Methods: Biphasic scaffolds from biomimetically mineralized salmon collagen and fibrillized jellyfish collagen were fabricated by joint freeze-drying and crosslinking. Different experiments were performed to analyze the influence of cell density and TGF-β on osteogenic differentiation of the cells in the scaffolds. Gene expression analysis and analysis of cartilage extracellular matrix components were performed and activity of alkaline phosphatase was determined. Furthermore, histological sections of differentiated cells in the biphasic scaffolds were analyzed. Results: Stable biphasic scaffolds from two different marine collagens were prepared. An in vitro setup for osteochondral differentiation was developed involving (1) different seeding densities in the phases; (2) additional application of alginate hydrogel in the chondral part; (3) pre-differentiation and sequential seeding of the scaffolds and (4) osteochondral medium. Spatially separated osteogenic and chondrogenic differentiation of hMSC was achieved in this setup, while osteochondral medium in combination with the biphasic scaffolds alone was not sufficient to reach this ambition. Conclusions: Biphasic, but monolithic scaffolds from exclusively marine collagens are suitable for the development of osteochondral constructs.

show abstract

“…In conclusion it is known that local and systemic concentrations of different osteogenic cytokines increase during physiological fracture healing, in particular sufficient serum concentrations of TGF-ß have been shown to be pivotal to fracture healing [ 36 ]. It has been reported that TGF-ß and BMPs are capable of inducing each others expressions [ 33 , 34 ], however patients with failed bone healing are known to have impaired local BMP concentration, furthermore the current study showed that the concentration of TGF-ß in concerned patients is decreased during the initial 12 months; indicating that BMP-7 and TGF-ß have to be present in fracture healing in a sufficient concentration [ 37 ]. Our results show that local application of BMP-7 serves as a substitution of impaired BMP-7 levels in non-union patients and thereby modulating the microenviroment in the fracture gap and promoting bone regeneration.…”

Section: Discussionmentioning

confidence: 65%

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy

et al. 2016

View full text Add to dashboard Cite

BackgroundIn this study we sought to determine if application of bone morphogenic protein 7 (BMP-7) promotes physiological bone healing of non-unions and to investigate if serum cytokine analysis may serve as a promising tool in the analysis of adjunct non-union therapy. Therefore we analyzed the influence of BMP-7 application on the serum cytokine expression patterns on patients with impaired bone healing compared to patients that showed proper bone healing.MethodsOur study involved analyzing blood samples from 208 patients with long bone fractures together with patients that subsequently developed non-unions. From this large pool, 15 patients with atrophic non-union were matched to 15 patients with atrophic non-union treated with local application of BMP-7 as well as normal bone healing. Changes in the cytokine expression patterns were monitored during the 1st, 2nd, 4th, 8th, 12th and 52nd week. The patients were followed both clinically and radiologically for the entire duration of the study. Serum cytokine expression levels of transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) were analyzed and compared.ResultsSerum expression of TGF-β were nearly parallel in all three groups, however serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05). bFGF serum concentrations increased initially in patients with proper bone healing and in those treated with BMP-7. Afterwards, values decreased; bFGF serum concentrations in the BMP-7 group were significantly higher than in the other groups (p < 0.05). PDGF serum concentration levels were nearly parallel in all groups, serum concentrations were significantly higher in patients with proper bone healing and those treated with BMP-7 than in patients with non-unions (p < 0.05).ConclusionTreatment with BMP-7 in patients with former non-unions led to similar cytokine expression patterns after treatment as those found in patients with proper bone healing. Our results suggest that treatment with BMP-7 promote healing of non-unions. Furthermore, quantitative measurement of serum cytokine expression is a promising tool for evaluating the effectiveness of additional non-union therapies such as adjunct application of growth factors.

show abstract

Induction of Osteogenic Differentiation in Human Mesenchymal Stem Cells by Crosstalk with Osteoblasts

Cited by 30 publications

References 21 publications

Osteogenic Programming of Human Mesenchymal Stem Cells with Highly Efficient Intracellular Delivery of RUNX2

Osteogenic Programming of Human Mesenchymal Stem Cells with Highly Efficient Intracellular Delivery of RUNX2

Biphasic Scaffolds from Marine Collagens for Regeneration of Osteochondral Defects

Non-unions treated with bone morphogenic protein 7: introducing the quantitative measurement of human serum cytokine levels as promising tool in evaluation of adjunct non-union therapy

Contact Info

Product

Resources

About