Open AccessmiRNA induced co-differentiation and cross-talk of adipose tissue-derived progenitor cells for 3D heterotypic pre-vascularized bone formation
Author(s) -
Nazmiye Celik,
Myoung-Hwan Kim,
Daniel J. Hayes,
İbrahim T. Özbolat
Publication year - 2021
Publication title -
biofabrication
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.328
H-Index - 80
eISSN - 1758-5090
pISSN - 1758-5082
DOI - 10.1088/1758-5090/ac23ae
Subject(s) - progenitor cell , microbiology and biotechnology , transfection , bone tissue , spheroid , cellular differentiation , cell , stem cell , osteoblast , biology , biomedical engineering , anatomy , cell culture , in vitro , gene , medicine , biochemistry , genetics
Engineered bone grafts require a vascular network to supply cells with oxygen, nutrients and remove waste. Using heterotypic mature cells to create these grafts in vivo has resulted in limited cell density, ectopic tissue formation and disorganized tissue. Despite evidence that progenitor cell aggregates, such as progenitor spheroids, are a potential candidate for fabrication of native-like pre-vascularized bone tissue, the factors dictating progenitor co-differentiation to create heterotypic pre-vascularized bone tissue remains poorly understood. In this study, we examined a three-dimensional heterotypic pre-vascularized bone tissue model, using osteogenic and endotheliogenic progenitor spheroids induced by miR-148b and miR-210 mimic transfection, respectively. Spheroids made of transfected cells were assembled into heterotypic structures to determine the impact on co-differentiation as a function of micro-RNA (miRNA) mimic treatment group and induction time. Our results demonstrated that miRNAs supported the differentiation in heterotypic structures, and that developing heterotypic structures is determined in part by progenitor maturity, as confirmed by gene and protein markers of osteogenic and endotheliogenic differentiation and the mineralization assay. As a proof of concept, miRNA-transfected spheroids were also bioprinted using aspiration-assisted bioprinting and organized into hollow structures to mimic the Haversian canal. Overall, the presented approach could be useful in fabrication of vascularized bone tissue using spheroids as building blocks.