Stemness and Osteogenic and Adipogenic Potential are Differently Impaired in Subcutaneous and Visceral Adipose Derived Stem Cells (ASCs) Isolated from Obese Donors

Abstract

Today adipose tissue is not just considered as the primary energy storage organ, but it is also recognized as an important endocrine tissue and an abundant source of mesenchymal stem cells (adipose-derived stem cells, ASCs). During the last decade, several studies have provided preclinical data on the safety and efficacy of ASCs, supporting their use in cell-based therapy for regenerative medicine purposes. Little is known about the effect of obesity on ASCs properties. Since ASCs differentiation and proliferation are determined by their niche, the differences in body fat distribution and the obesity-related co-morbidities may have several consequences. In this study we compared ASCs of subcutaneous adipose tissue from obese (obS-ASCs) and non-obese (nS-ASCs) donors in order to compare their immunophenotype and osteogenic and adipogenic potential. Moreover, in order to evaluate the possible difference between subcutaneous and visceral fat, obS-ASCs were also compared to ASCs derived from visceral adipose tissue of the same obese donors (obV-ASCs). Our results show that subcutaneous and visceral ASCs derived from obese donors have an impaired cell proliferation, clonogenic ability and immunophenotype. Nevertheless, obS-ASCs are able to differentiate toward osteogenic and adipogenic lineages, although to a small extent with respect to non-obese donors, whereas obV-ASCs lose most of their stem cell characteristics, including multi-differentiation potential. Taken together our findings confirm that not all ASCs present the same behavior, most likely due to their biological microenvironment in vivo. The specific stimuli which can play a key role in ASCs impairment, including the effects of the obesity-related inflammation, should be further investigated to have a complete picture of the phenomenon.

Analysis of Biological Properties of Human Adult Mesenchymal Stem Cells and Their Effect on Mouse Hind Limb Ischemia

“…The AMSC from other donors and harvest sites clearly differentiated to several mesenchymal lineages. Thus, AMSC niche seems to determine their proliferation and differentiation capability [20, 21, 32, 33]. These results are in agreement with the existing publications in which it is argued that the capacity of differentiation (multipotency), even migration and proliferation of the AMSC, decreases when the body mass index of the donor increases [45-47].…”

“…AMSC from the abdomen of obese donors had the surface markers for MSC but their stemness capacity was severely limited, only differentiating into adipocytes. This may be due to them being in a more differentiated stage, as has been reported by DiGirolano [32]. The AMSC from other donors and harvest sites clearly differentiated to several mesenchymal lineages.…”

Age-Related Effects on the Potency of Human Adipose-Derived Stem Cells: Creation and Evaluation of Superlots and Implications for Musculoskeletal Tissue Engineering Applications

“…It is likely that hASC derived from healthy patients will exhibit a different differentiation profile from those derived from severely obese patients. 31,32 Other sources of variation may include the specific medical procedure with which a tissue was obtained, however, it is likely that patient physiology may have the greatest influence. This may partially explain the high level of donor-to-donor variation across age groups.…”

Comparison of Stromal/Stem Cells Isolated from Human Omental and Subcutaneous Adipose Depots: Differentiation and Immunophenotypic Characterization

“…Both ASC and BMSC share a similar differentiation and immunophenotypic profile; however, a unit volume of adipose tissue yields nearly two to three orders of magnitude more ASC at the initial passage as a similar volume of bone marrow Pachon-Pena et al, 2011]. Consequently, there has been a growing interest in the regenerative medical potential of ASC from multiple adipose depots [Wickham et al, 2003;Baglioni et al, 2009;Villaret et al, 2010;De Girolamo et al, 2013;Pires de Carvalho et al, 2014;Russo et al, 2014]. To address this question, we have compared the differentiation and immunophenotypic characteristics between ASC derived from omental adipose depots of subjects undergoing elective bariatric surgery and ASC from subcutaneous adipose depots of subjects undergoing elective plastic surgery.…”