From fat/adipose to engineered bone organ

There has been an increasing interest in the use of biomimetic and cell-seeded scaffolds in regenerative medicine and bone tissue engineering. Although the use of adipose tissue-derived cells as scaffolding materials exhibits great clinical importance, some of the steps involved in the generation of osteogenic grafts (such as monolayer expansion and the passage of human adipose stromal cells) strongly reduce their differentiation potential. Moreover, factors such as cost, time constraints and the demanding conditions for the clinical implementation of osteogenic engineering limits the successful use of osteogenic grafts. Thus, researchers have explored alternative ways to generate osteogenic grafts for bone repair. Recent studies have indicated that the regenerative cells isolated from human adipose tissue can be combined with 3D scaffolds to generate osteogenic grafts for the treatment of bone defects. This tissue may be used as scaffolding material to support the endochondral differentiation of adipose stromal cells (ASCs). Moreover, the unique structural properties and high density of stromal progenitors in fractionated adipose tissues makes it suitable for the repair of bone tissues.

Recently, University of Basel Hospital scientists led by Dr. Arnaud Scherberich investigated the direct use of human fractionated liposuction samples as a cellularized biomaterial for the in vitro generation of cartilage and hypertrophic cartilage tissues. They demonstrated the formation of a bone organ from human adipose tissues by endochondral ossification. The work is published in the peer-reviewed journal, Acta Biomaterialia.

The research team cultured fractionated adipose in suspension for 3 weeks to let the ASCs proliferate inside the native tissue and obtained a construct referred to as Adiscaf. They then observed the efficient formation of cartilaginous tissues in the Adiscaf after four weeks of chondrogenic differentiation. These constructs contained high amount of glycosaminoglycan and collagen type II. The starting size of Adiscaf was maintained after 4 weeks in chondrogenic medium and 2 additional weeks with hypertrophic medium. The authors also observed the upregulation of hypertrophic markers at the protein and gene expression levels.

The native adipose constructs resulted in the formation of ectopic bone tissue and bone marrow elements after 8 weeks of in vivo implantation. The Adiscaf constructs exhibited superior in vivo performance and in vitro differentiation compared to collagen sponge-based constructs (i.e. control paradigm) that involved the isolation and monolayer expansion of ASCs from the same donors.

Indeed the study by Dr. Arnaud Scherberich and colleagues provides compelling evidence that adult human adipose tissues can be used as native constructs for the formation of bones. The Swiss research group developed protocols that facilitate the induction, characterization, expansion, new matrix formation and hypertrophic differentiation of ASCs in vitro, evaluated ectopic bone formation by native constructs and validated the occurrence of endochondral ossification by confirming the presence of bone marrow elements in vivo after implantation. These findings will advance development of an innovative clinical approach for the regeneration and repair of bones.