Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification

Abstract

Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice.

Notch‐inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate

“…Human bone marrow-derived mesenchymal stem cells (BM-MSCs) were isolated as described previously [58] from bone marrow aspirates of healthy donors obtained during orthopedic surgical procedures after informed consent and in accordance with the local ethical committee (University Hospital Basel; Prof. Dr. Kummer; approval date 26/03/2007 Ref Number 78/07). Human adipose-derived stromal cells (ASCs) were isolated as described previously [59,60] from adipose tissue obtained during routine surgical procedures of healthy donors after informed consent and in accordance with the local ethical committee (Ethikkommission beider Basel [EKKB], Ref Number 78/07). ASCs and BM-MSCs were maintained in MEM alpha (with nucleosides, Gibco) supplemented with FBS (10%, Gibco), penicillin (100 U/ml, Gibco), streptomycin (100 lg/ml, Gibco), and FGF-2 (5 ng/ml, PeproTech).…”

Endochondral Bone Regeneration by Non-autologous Mesenchymal Stem Cells

“…Over the last decade, tissue engineering has successfully mimicked this process to regenerate bone defects in vivo (Thompson et al, 2015 ). Various types of cells, including multipotent mesenchymal stromal cells (MSCs) (Scotti et al, 2013 ; Harada et al, 2014 ; van der Stok et al, 2014 ; Matsiko et al, 2018 ; McDermott et al, 2019 ), embryonic stem cells (Jukes et al, 2008 ) and adipose-derived stem cells (Osinga et al, 2016 ) were used alone or in combination with biomaterials to develop a cartilaginous template that, upon implantation, would trigger new bone formation. Despite these promising results, the clinical translation of endochondral bone regeneration (EBR) is in an early stage for several reasons.…”

Bone Tissue Engineering Using Human Cells: A Comprehensive Review on Recent Trends, Current Prospects, and Recommendations

“…The ease of availability, high yield of cell isolation, and excellent proliferation rate are considered the main reasons for the use of ASCs in bone regeneration [199]. It has been shown that one gram of adipose tissue yields about 5 × 10 3 stem cells, which is 500-fold greater than the number of cells obtained from one gram of bone marrow [200][201][202].…”