ABSTRACT
Title
Human adipose-derived stem cells (hASCs) from obese patients and their feasible use in cell-based therapies
Authors
D. Stanco1,3, E. Arrigoni1,2, L. de Girolamo3, L. Salvatori4, S. Niada1,2, V. Yenagi1,2, E. Petrangeli4, A.T. Brini1*
1 Department of Medical Pharmacology, School of Medicine, Università degli Studi di Milano, Milan, Italy
2 PhD Student of Graduate School of Pharmacological Sciences, Università degli Studi di Milano, Milan, Italy
3 IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
4 Experimental Medicine and Pathology Department, Università di Roma “La Sapienza”, Rome, Italy
1 Department of Medical Pharmacology, School of Medicine, Università degli Studi di Milano, Milan, Italy
2 PhD Student of Graduate School of Pharmacological Sciences, Università degli Studi di Milano, Milan, Italy
3 IRCCS Galeazzi Orthopaedic Institute, Milan, Italy
4 Experimental Medicine and Pathology Department, Università di Roma “La Sapienza”, Rome, Italy
Abstract
Cell-based therapies, such as tissue engineering, provide promising therapeutic possibilities to enhance the repair or regeneration of damaged or diseased tissues, but they are dependent on the availability of appropriate cell sources. In recent years, there has been a growing emphasis on the use of mesenchymal stem cells derived from adipose tissue (ASCs), owing to their ability to be expanded in culture and to differentiate into multiple cell types similar to other adult stem cells, such as bone marrow mesenchymal stem cells (de Girolamo et al., 2009). The major advantages of using such cells are their easy availability through standard liposuction procedures and their abundance in normal human fat.
However, some pathological conditions, like obesity, may influence the features of human adipose-derived stem cells (hASCs). Indeed, obesity is known to be associated with recruited macrophages into adipose tissue and it is combined by a chronic low-grade inflammation which is correlated with a reduced tissutal pressure of oxygen (Weisberg et al.,2004; Trayhurn et al., 2004). Some of these factors could affect the properties of hASCs, and for this reason, we have isolated hASCs from subcutaneous adipose tissue of normal-weight donors (nS-hASCs, n=5, mean age 33±6 years, BMI=24±2) and from pathological obese donors (ObS-hASCs, n=5, mean age 43±10 years, mean BMI=43±5). We have also collected visceral adipose tissue (ObV-hASCs, n=5) in order to evaluate possible differences in the expression of the inflammatory phenotype. We have compared hASCs clonogenicity, immunophenotype and osteogenic potential.
The clonogenic potential is significantly lower in ObS-hASCs than in normal-weight donors (-51%), and, among obese patients, it is greater in subcutaneous hASCs than in omental ones (+142%).
ObS-hASCs show a significantly lower proliferation rate in comparison to nS-hASCs (-40%); moreover ObV-hASCs grow slower than their corresponding subcutaneous cells (-29%). hASCs from obese donors show a typical mesenchymal stem cells immunophenotype, even if the expression of CD54, CD90 and CD166 appears significantly reduced respect to normal-weight patients. The osteogenic potential of hASCs is also affected by obesity: indeed, a significant reduction in the alkaline phosphatase activity and in calcified extracellular matrix deposition was observed.
Moreover, preliminary data suggest that both ObS- and ObV-hASCs are responsive to hypoxic treatment since pro-inflammatory genes have been activated, despite the fact that the observed modulation is quite different in the two cell types.
In conclusion, obesity seems to negatively affect some abilities of hASCs, most likely related to the inflammatory state of this pathological condition. Our data suggest that the use of hASCs in tissue engineering applications may depend on the patho/physiological conditions of the donors. We may also assume that the study of adipose tissue or its components will provide some knowledge for the future treatments for some metabolic disorders, and in particular about their long-term safety and benefits compared with the actual therapies.
This study was partially supported by grants from FINALIZZATA 2007 and from Italian Ministry of University and Research.
Weisberg (2003). J Clin Invest 112, 1796–1808.
Trayhurn (2004). Br J Nutr 92, 347–355.
de Girolamo (2009). Cytotherapy 11(6), 793-803.
However, some pathological conditions, like obesity, may influence the features of human adipose-derived stem cells (hASCs). Indeed, obesity is known to be associated with recruited macrophages into adipose tissue and it is combined by a chronic low-grade inflammation which is correlated with a reduced tissutal pressure of oxygen (Weisberg et al.,2004; Trayhurn et al., 2004). Some of these factors could affect the properties of hASCs, and for this reason, we have isolated hASCs from subcutaneous adipose tissue of normal-weight donors (nS-hASCs, n=5, mean age 33±6 years, BMI=24±2) and from pathological obese donors (ObS-hASCs, n=5, mean age 43±10 years, mean BMI=43±5). We have also collected visceral adipose tissue (ObV-hASCs, n=5) in order to evaluate possible differences in the expression of the inflammatory phenotype. We have compared hASCs clonogenicity, immunophenotype and osteogenic potential.
The clonogenic potential is significantly lower in ObS-hASCs than in normal-weight donors (-51%), and, among obese patients, it is greater in subcutaneous hASCs than in omental ones (+142%).
ObS-hASCs show a significantly lower proliferation rate in comparison to nS-hASCs (-40%); moreover ObV-hASCs grow slower than their corresponding subcutaneous cells (-29%). hASCs from obese donors show a typical mesenchymal stem cells immunophenotype, even if the expression of CD54, CD90 and CD166 appears significantly reduced respect to normal-weight patients. The osteogenic potential of hASCs is also affected by obesity: indeed, a significant reduction in the alkaline phosphatase activity and in calcified extracellular matrix deposition was observed.
Moreover, preliminary data suggest that both ObS- and ObV-hASCs are responsive to hypoxic treatment since pro-inflammatory genes have been activated, despite the fact that the observed modulation is quite different in the two cell types.
In conclusion, obesity seems to negatively affect some abilities of hASCs, most likely related to the inflammatory state of this pathological condition. Our data suggest that the use of hASCs in tissue engineering applications may depend on the patho/physiological conditions of the donors. We may also assume that the study of adipose tissue or its components will provide some knowledge for the future treatments for some metabolic disorders, and in particular about their long-term safety and benefits compared with the actual therapies.
This study was partially supported by grants from FINALIZZATA 2007 and from Italian Ministry of University and Research.
Weisberg (2003). J Clin Invest 112, 1796–1808.
Trayhurn (2004). Br J Nutr 92, 347–355.
de Girolamo (2009). Cytotherapy 11(6), 793-803.