Abstract
BackgroundCraniomaxillofacial defects secondary to trauma, tumor resection, or congenital malformations are frequent unmet challenges, due to suboptimal alloplastic options and limited autologous tissues such as bone. Significant advances have been made in the application of adipose-derived stem/stromal cells (ASCs) in the pre-clinical and clinical settings as a cell source for tissue engineering approaches. To fully realize the translational potential of ASCs, the identification of optimal donors for ASCs will ensure the successful implementation of these cells for tissue engineering approaches. In the current study, the impact of obesity on the osteogenic differentiation of ASCs was investigated.MethodsASCs isolated from lean donors (body mass index <25; lnASCs) and obese donors (body mass index >30; obASCs) were induced with osteogenic differentiation medium as monolayers in an estrogen-depleted culture system and on three-dimensional scaffolds. Critical size calvarial defects were generated in male nude mice and treated with scaffolds implanted with lnASCs or obASCs.ResultslnASCs demonstrated enhanced osteogenic differentiation in monolayer culture system, on three-dimensional scaffolds, and for the treatment of calvarial defects, whereas obASCs were unable to induce similar levels of osteogenic differentiation in vitro and in vivo. Gene expression analysis of lnASCs and obASCs during osteogenic differentiation demonstrated higher levels of osteogenic genes in lnASCs compared to obASCs.ConclusionCollectively, these results indicate that obesity reduces the osteogenic differentiation capacity of ASCs such that they may have a limited suitability as a cell source for tissue engineering.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0776-1) contains supplementary material, which is available to authorized users.
Highlights
Craniomaxillofacial defects secondary to trauma, tumor resection, or congenital malformations are frequent unmet challenges, due to suboptimal alloplastic options and limited autologous tissues such as bone
Critical size calvarial defects were generated in nude mice and treated with scaffolds seeded with adipose-derived stem/stromal cells (ASCs) isolated from lean or obese donors
These findings indicate that obesity significant reduces the osteogenic capacity of ASCs and that ASCs isolated from obese donors may be suboptimal as the cell source for tissue engineering applications
Summary
Human subjects Primary human ASCs were obtained from subcutaneous abdominal adipose tissue of 12 Caucasian females undergoing elective liposuction. ObASCs demonstrate reduced osteogenic differentiation potential in a growth factor depleted environment To characterize the osteogenic potential of lnASCs and obASCs, these cells were induced with ODM for 21 days and calcium deposition was visualized with Alizarin Red staining. To determine whether delivery of estradiol would restore the osteogenic differentiation in obASCs, cells were induced with CDS-ODM supplemented with log fold increases of estradiol from 100 pM to 10 μM Both lnASCs and obASCs demonstrated enhanced osteogenic differentiation in the presence of estradiol (Additional file 1: Fig. S1). By 16 weeks, mice treated with scaffolds generated more calcified regions (2.1-fold increase) compared to mice in the control group; these results were not statistically significant (Fig. 3). LnASCs cultured in CDS-ODM demonstrated a biphasic upregulation of COLA1a by 33.6-fold and 135.7-fold after 7 and 21 days, respectively (Fig. 6)
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