Matteo Centola, PhD
Tendons are responsible for generating movement and are cyclically exposed to immense stresses, upward of 100 megapascals. Tendons are thus highly prone to injury and their hypocellularity and hypovascularity make their natural healing extremely slow and inefficient. Surgical repair strategies are common but often unsuccessful.
The new drug-discovery initiative within the Musculoskeletal Disease Area (MSD) aims at improving tendon repair and developing effective treatments for tendinopathy. These efforts will profit from an expansion of the currently limited knowledge on (i) the molecular mechanisms that control embryonic tendon development, and (ii) the differentiation of resident tendon (stem/progenitor) cells in the adult tissue.
We aim to develop robust in vitro differentiation protocols to engineer 3D tendon niches that simulate the mechanobiology of the native tissue. Building on knowledge of tendon embryonic development, we wish to drive the differentiation of pluripotent stem cells and adult tendon-derived cells by (i) temporally-controlled delivery of morphogens mimicking the normal tendon developmental pathway and (ii) dynamic biomechanical stimulation of the engineered tissue to achieve a mature cell differentiation.
The organoids generated in this project will serve as models for testing drug efficacy. Introducing the third dimension into drug-discovery research is anticipated to provide the key missing link between in vitro and in vivo assays, as conventional 2D cell culture only partially mimics the complexity of the tissue microenvironment.
Tissue engineering strategies to study cartilage development, degeneration and regeneration.
Bhattacharjeea M*, Coburnb J*, Centola M*, Muraba S, Barbero A, Kaplan DL, Martin I, Ghosha S.
Adv Drug Del Rev. 2014 in press.
*equally contributing authors
Re-engineering development to instruct tissue regeneration.
Tonnarelli B, Centola M, Barbero A, Zeller R, Martin I.
Curr Top Dev Biol. 2014;108:319-38.
Priming 3D cultures of human mesenchymal stromal cells toward cartilage formation via developmental pathways.
Centola M, Tonnarelli B, Schären S, Glaser N, Barbero A, Martin I.
Stem Cells Dev. 2013 Nov;22(21):2849-58.
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