Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5653_Библиотеки_им_академика_М_И_Перельмана

brils into bers compact enough to mimic the superbrillar organisation of natural tissues [112]. Decorin gene expressionwas consistently upregu­lated to a signicant extentupon osteogenic induc­tion of hBM-MSC despite different contexts; (i) when hBMSC-TERT cells were cultured as 3D osteospheroids [22], (ii) in primary hBM-MSC cul­tured in either Fetal Bovine Serum or Platelet lysate [100] and (iii) when the primary hBM-MSC were tested in another laboratory using different batches of growth medium and a different osteoinduction medium formulation [101]. Thus, decorin repre­sents a biomarker that could qualify as being ‘robustly expressed’ across different cell expansion platforms. The fold-change in hBMSC- TERT DCN mRNA expression was >3-fold for monolayer cul­tures or >2-fold for 3D cultures osteogenically induced in FBS containing medium. For monolayer cultures of primary hBM-MSC grown with platelet lysateinstead of FBS, theDCN- specic transcript expression typically increased 20 to 30-fold after just 1 week of osteogenic induction and this was reproducible despite use of alternative osteogenic induction agents across different laboratories [101]. Good for potency biosensing purposes, signicant changes in decorin expression occurred early in the induced transition from precursor cell to osteoblast [34, 35, 65, 97, 98, 155]. Beyond inuencing colla- gen bril organisation, preventing aberrant prema­ture osteoid mineralisation, decorin is likely to have an important role in blocking excess TGF-ß signal­ing from inhibiting osteoblast maturation [19]. Although TGF-ß1 is required for optimal bone for­mation [19, 20, 52, 61, 144, 164], high doses of TGF-ß1 could suppress mineralisation in an ortho­topic implant model [20]. Decorin can interact directly with all three TGF-ß protein isoforms [62,

the cells in culture, required to perform some osteogenic potency assay tests, already intro­duces additional need for quality and safety con­trols for the relevant reagents. Noteworthy alternative differentiation methods include use of osteoinductive materials such as graphene oxide composites [78] or introduction of nano vibra­tions [64] as procedures that can stimulate innate potent bioactive metabolites that specically potentiate osteogenesis, without incurring the potential artefact of an arbitrarily derived exvivo differentiation factor. Furthermore, experimental models have demonstrated that both siRNA [5] and microRNA [106] can be used to functionalise scaffolds to inuence multilineage differentiation and accelerate bone regeneration, although potency assays that incorporate the contribution of scaffold dynamics are at an early stage of development. Notably, for the compromised cir­cumstances found in large bone fractures, the cel­lular component combined with the scaffold was signicant for repair [79]. Additional approaches, exploring whether scaffolds can be engineered to encourage activation of endogenous cells to regenerate the appropriate skeletal tissue healing are under development [8].