Elsevier

Experimental Cell Research

Volume 314, Issue 7, 15 April 2008, Pages 1575-1584
Experimental Cell Research

Research Article
Cell specific differences between human adipose-derived and mesenchymal–stromal cells despite similar differentiation potentials

https://doi.org/10.1016/j.yexcr.2007.12.022Get rights and content

Abstract

Stromal cells from bone marrow and adipose tissue are attractive sources of adult progenitors for cell-based therapy. However, whether those cell populations represent intrinsically different cell types is still largely under debate. The aim of this study was to systematically and quantitatively compare adipose-derived stromal cells (ADSC) and bone marrow-derived multipotent mesenchymal–stromal cells (BM-MSC). The quantitative comparison was realized using Taqman Low Density Array, 2D electrophoresis and differentiation functional assays in vitro. Furthermore, cells engineered to express TGFβ1 were injected into the intra-articular space of mouse knee joints in order to determine whether they were able to form new differentiated tissues in vivo. Our data revealed cell specific differences at transcriptional and proteomic levels between both cell types according to their tissue origin as well as functional differences in their differentiation processes towards adipogenic, osteogenic and chondrogenic programs. Nevertheless, in vitro as well as in vivo ADSC displayed the same ability than MSC to differentiate towards chondrocytes/osteoblasts, comforting the status of both cell sources as promising regenerative cells. In summary, our observations indicate that ADSC and MSC are fundamentally different cell types and differently committed cells.

Introduction

Adipose tissue appears as a suitable reservoir of regenerative cells as this adult tissue is abundant and easy to sample with no ethic limitation. Recent works from independent groups state that adipose tissue hosts cells able to display various differentiation potentials in vitro and in vivo [1], [2], [3], [4]. Such cells can be isolated from the stroma vascular fraction (SVF) obtained after adipose tissue digestion that may be used either freshly prepared or after sub-culture [2], [4], [5], [6], [7]. In this last case, cultured cells represent a particular cell subpopulation, restricted to the adherent cell fraction of SVF, termed ADSC (adipose-derived stromal cells).

ADSC are often called adipose-derived mesenchymal stem cells (MSC), as MSC represent an archetype of adult stem cells. MSC are classically isolated from bone marrow (BM) aspirates and are identified as a multipotent cell population in the adult organism able to be induced to express adipogenic, osteogenic and chondrogenic markers [8], [9], [10], [11] and especially studied in the context of bone/cartilage regeneration in vivo [12], [13], [14]. Although stromal cells from BM and adipose tissue seem to be closely related, notable differences were reported [6], [15], [16], [17], [18], [19], but no systematic and extensive parallel comparison between these cells has yet been performed. According to the large perspective opened by the easy access to an abundant source of regenerative cells, such study seems requested.

The objective of this study was to realize such comparison on the biological characteristics of ADSC and MSC both in vitro and in vivo. Indeed, two dimensional gel electrophoresis and real-time PCR based Taqman Low Density Array (TLDA) covering differentiation, stemness and signalling pathways, were used to establish, respectively, a proteomic and transcriptional profile of both cell populations. In addition, we analysed their phenotype as well as their differentiation potential in vitro. In vivo, cells were injected into the intra-articular space of mouse knee joints to determine their capacity to differentiate in an in vivo cartilaginous environment.

Section snippets

Cell culture

The SVF was isolated from human adipose tissue as previously described [4]. Human subcutaneous fat was obtained from healthy patients undergoing abdominal dermolipectomy in the department of Plastic Surgery of Toulouse Rangueil Hospital (Toulouse, France). The patients were between 20 and 50 years old and their BMI never over 30. SVF cells were plated overnight in DMEM-F12 (1:1) medium supplemented with 10% FBS, 100 μg/ml pantothenic acid, 100 μM ascorbic acid, 16 μM biotin, 250 μg/ml

Phenotypic characterization of ADSC and MSC

After isolation, both MSC and ADSC exhibited fibroblast-like cell morphology. Both cells were positive for known mesenchymal markers such as CD73 and CD90 and negative for the haematopoietic marker CD45 (Fig. 1). As previously described [4], [5], [9], [23], [24]CD44 and CD105 were also expressed by both cell types, while CD31 was not detected (data not shown). MSC expressed CD106 (VCAM1), an adhesion molecule found on vascular cells that mediates the binding of haematopoietic progenitors on MSC

Acknowledgments

Caton D. and Roche S. as well as the study are financially supported by the European Community (Key action LSH 1.2.4-3, Integrated project: “Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side”, Contract no: 503161), the Cell and Gene Therapy program from Région Midi-Pyrénées (#03011999), and the Etablissement Français du Sang.

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