Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity

Abstract

The identification of multipotent adipose-derived stromal cells (ASC) has raised hope that tissue regeneration approaches established with bone-marrow-derived stromal cells (BMSC) can be reproduced with a cell-type that is far more accessible in large quantities. Recent detailed comparisons, however, revealed subtle functional differences between ASC and BMSC, stressing the concept of a common mesenchymal progenitor existing in a perivascular niche across all tissues. Focussing on bone and cartilage repair, this review summarises recent in vitro and in vivo studies aiming towards tissue regeneration with ASC. Advantages of good accessibility, high yield and superior growth properties are counterbalanced by an inferiority of ASC to form ectopic bone and stimulate long-bone healing along with their less pronounced osteogenic and angiogenic gene expression signature. Hence, particular emphasis is placed on establishing whether stem cell activity of ASC is so far proven and relevant for successful osteochondral regeneration, or whether trophic activity may largely determine therapeutic outcome.

Repair of Torn Avascular Meniscal Cartilage Using Undifferentiated Autologous Mesenchymal Stem Cells: From In Vitro Optimization to a First-in-Human Study

“…Stem cell therapy is in its infancy and we are only gradually understanding how best to use these cells in the clinical setting. While much research effort has concentrated on understanding how we can effectively differentiate MSCs to specific committed lineages [23,[31][32][33][34][35][36][37][38][39][40][41], there has been growing interest in the trophic effects of the undifferentiated cells mediated through secretion of growth factors [13][14][15][16][17]. Based on our original in vitro observations [12] we hypothesized that combining undifferentiated MSCs with a collagen scaffold, we could deliver the cells directly into the site of injury and maximize the chance of secreted trophic factors driving a tissue repair response.…”

Combined delivery of FGF‐2, TGF‐β1, and adipose‐derived stem cells from an engineered periosteum to a critical‐sized mouse femur defect

“…However, a statistically significant increase in bone was not found in ASC‐treated allografts suggesting ASC delivery alone or with co‐delivered FGF‐2 and TGF‐β1 was insufficient for robust new bone formation. It has been previously reported that ASCs may have less of an osteogenic potential than similar mesenchymal stem cells derived from bone marrow cells and require osteogenic pre‐induction before implantation for robust bone formation . The ASCs used in this experiment were not osteogenically induced prior to implantation.…”

Combined treatment with platelet-rich plasma and insulin favours chondrogenic and osteogenic differentiation of human adipose-derived stem cells in three-dimensional collagen scaffolds

“…Current treatments of osteochondral defects by reconstructive plastic and orthopaedic surgery procedures are unable to restore the function of damaged tissues; they are only palliative and not curative (Orth et al , ). Tissue engineering has been proposed as an alternative strategy to repair osteochondral defects (Ruetze and Richter, ; Veronesi et al , ) and a potential alternative to regenerate bone, cartilage and the bone–cartilage interface (Nukavarapu and Dorcemus, ). New strategies of tissue engineering strongly support the simultaneous use of scaffolds, cells and growth factors (Hosseinkhani et al ., ).…”