Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation

Bondarava, Maryna; Cattaneo, Chiara; Ren, Bin; Thasler, Wolfgang E.; Jansson, Volkmar; Müller, Peter E.; Betz, Oliver B.

doi:10.1038/srep39712

Cited by 9 publications

(9 citation statements)

References 66 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The question whether the osteogenic differentiation capacity or the potential to deliver high levels of transgene is more important for effective bone regeneration can only be answered by future in vivo experiments. Interestingly, recent in vitro studies could prove that human fat tissue (Bondarava et al, ) and human muscle tissue (Miao et al, ) can transdifferentiate into mineralized tissue with bone‐like characteristics. These results suggest that the grafted gene‐activated tissue fragments used in the experiments of Betz and colleagues (Betz et al, ; Betz et al, ) contributed to the formation of new bone in vivo through transdifferentiation and not only through the local effects of the delivered BMP on the environment of the lesion.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Gene‐activated tissue grafts for sustained bone morphogenetic protein‐2 delivery and bone engineering: Is muscle with fascia superior to muscle and fat?

Ren

Betz

Thirion³

et al. 2017

J Tissue Eng Regen Med

Self Cite

View full text Add to dashboard Cite

Previously, we have presented an expedited strategy for sustained delivery of bone morphogenetic protein-2 (BMP-2) to bone lesions based on the implantation of gene-activated fat and muscle fragments. The aim of the present in vitro experiments was to evaluate the potential of muscle with fascia as a BMP-2 delivering osteo-regenerative implant in comparison to fat tissue and muscle alone. Subcutaneous fat, muscle, and muscle with fascia were harvested from Fischer 344 rats. The tissues were cut into small pieces and cultured for up to 90 days after direct transduction with adenoviral BMP-2 or green fluorescence protein vectors. Different vector doses were applied, and proliferation, long-term BMP-2 production, and osteogenic differentiation of the 3 different tissues were investigated in vitro. Muscle with fascia produced the largest amounts of BMP-2. Expression of the transgene was detected for up to 90 days. Proliferation was reduced with increased vector doses. Muscle with fascia showed a higher potential for osteogenic differentiation than fat, but it was not improved as compared to muscle alone. A dose of 4 × 10 plaque forming units of the adenoviral BMP-2 vector appeared to be the optimal dose for transduction of muscle with fascia. Because muscle with fascia produced higher amounts of BMP-2 as compared to muscle alone or fat tissue grafts, showing a high potential for osteogenic differentiation, it might represent an improved osteo-regenerative implant facilitating endogenous repair. Future studies should investigate the effect of muscle with fascia transduced with 4 × 10 plaque forming units on bone healing in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The implantation of BMP‐2 gene‐activated fat led to fast and robust structural and functional healing of femoral defects. Moreover, in recent work, it could be demonstrated that human fat tissue can transdifferentiate into bone‐like tissue (Bondarava et al, ).…”

Section: Introductionmentioning

confidence: 99%

Gene‐activated tissue grafts for sustained bone morphogenetic protein‐2 delivery and bone engineering: Is muscle with fascia superior to muscle and fat?

Ren

Betz

Thirion³

et al. 2017

J Tissue Eng Regen Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…For hADSCs, cells were donated to our lab by Maryna et al . 69 , whereas chondrocytes and hBMSCs were obtained from Lonza (Lonza, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

Recommendations for improving accuracy of gene expression data in bone and cartilage tissue engineering

Huang

Chak

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Autogenous tissue grafting remains the gold standard in the treatment of critical sized bone and certain cartilage defects, while the translation of tissue engineered osteogenesis or chondrogenesis from the lab bench into clinical practice, utilizing natural or synthetic biomimetic devices, remains challenging. One of the crucial underestimated reasons for non-translatability could be the imprecision and inconsistency of generated gene expression profiles, utilizing improperly optimized and standardized quantitative gene assays. Utilizing GeNorm for downstream qRT-PCR applications, the stability of reference genes in relation to optimal cDNA amounts was assessed on human bone marrow-derived mesenchymal and adipose-derived stem cells neat and made to differentiate into chondrocytes including normal human derived chondrocytes and muscle tissue from rats. Results showed that reference genes can vary substantially across separately and/or combined cell lines and/or tissue types including treatment parameters. The recommendations to all bone and cartilage tissue engineers utilizing qRT-PCR is not to assume that reference gene stability and quantity remain conserved across cell lines or tissue types but to always determine, for each new experiment, the stability and normalization quantity of reference genes anew.

show abstract

“…The authors attributed the compromised results to large defect sizes, rapid resorption of the ceramic scaffolds, and possibly the lack of osteoinductive signals in the form of rhBMP‐2. In context, a recent study demonstrated enhanced osteogenic differentiation of cells from “whole adipose tissue” stimulated by rhBMP‐2 compared to stimulation by osteogenic medium alone (Bondarava et al., ).…”

Section: Discussionmentioning

confidence: 99%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

View full text Add to dashboard Cite

Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

show abstract

Osseous differentiation of human fat tissue grafts: From tissue engineering to tissue differentiation

Cited by 9 publications

References 66 publications

Gene‐activated tissue grafts for sustained bone morphogenetic protein‐2 delivery and bone engineering: Is muscle with fascia superior to muscle and fat?

Gene‐activated tissue grafts for sustained bone morphogenetic protein‐2 delivery and bone engineering: Is muscle with fascia superior to muscle and fat?

Recommendations for improving accuracy of gene expression data in bone and cartilage tissue engineering

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Contact Info

Product

Resources

About