title: Reconstitution of bone-like matrix in osteogenically differentiated mesenchymal stem cell-collagen constructs: A three-dimensional in vitro model to study hematopoietic stem cell niche.
abstract: Mesenchymal stem/stromal cells (MSCs) and osteoblasts are important niche cells for hematopoietic stem cells (HSCs) in bone marrow osteoblastic niche. Here, we aim to partially reconstitute the bone marrow HSC niche in vitro using collagen microencapsulation for investigation of the interactions between HSCs and MSCs. Mouse MSCs (mMSCs) microencapsulated in collagen were osteogenically differentiated to derive a bone-like matrix consisting of osteocalcin, osteopontin, and calcium deposits and secreted bone morphogenic protein 2 (BMP2). Decellularized bone-like matrix was seeded with fluorescence-labeled human MSCs and HSCs. Comparing with pure collagen scaffold, significantly more HSCs and HSC-MSC pairs per unit area were found in the decellularized bone-like matrix. Moreover, incubation with excess neutralizing antibody of BMP2 resulted in a significantly higher number of HSC per unit area than that without in the decellularized matrix. This work suggests that the osteogenic differentiated MSC-collagen microsphere is a valuable three-dimensional in vitro model to elucidate cell-cell and cell-matrix interactions in HSC niche.
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Wy
authors.initials: W
authors.lastname: Lai
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Yy
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Sk
authors.initials: S
authors.lastname: Mak
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Fc
authors.initials: F
authors.lastname: Ho
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: St
authors.initials: S
authors.lastname: Chow
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Wh
authors.initials: W
authors.lastname: Chooi
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Ch
authors.initials: Ch
authors.lastname: Chow
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Ay
authors.initials: A
authors.lastname: Leung
authors.affiliation: Tissue Engineering Laboratory, Medical Engineering Program, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region, China.
authors.forename: Bp
authors.initials: B
authors.lastname: Chan
keywords: Osteogenic differentiation; decellularization; hematopoietic stem cells; in vitro model; mesenchymal stem/stromal cell; niche