Abstract
Adipose tissue-derived stromal cells (ADSCs) are of interest for regenerative medicine as they are isolated easily and can differentiate into multiple cell lineages. Studies of their in vitro proliferation, survival, and differentiation are common; however, genetic effects on these phenotypes remain unknown. To test if these phenotypes are genetically regulated, ADSCs were isolated from three genetically diverse inbred mouse strains- C57BL/6J (B6), BALB/cByJ (BALB), and DBA/2J (D2)- in which genetic regulation of hematopoietic stem function is well known. ADSCs from all three strains differentiated into osteogenic and chondrogenic lineages in vitro. ADSCs from BALB grew least well in vitro, probably due to apoptotic cell death after several days in culture. BALB ADSCs were also the most susceptible to the free radical inducers menadione and H2O2. ADSCs from the three possible F1 hybrids were employed to further define genetic regulation of ADSC phenotypes. D2, but not B6, alleles stimulated ADSC expansion in BALB cells. In contrast, B6, but not D2, alleles rescued BALB H2O2 resistance. We conclude that low oxidative stress resistance does not limit BALB ADSC growth in vitro, as these phenotypes are genetically regulated independently. In addition, ADSCs from these strains are an appropriate model system to investigate genetic regulation of ADSC apoptosis and stress resistance in future studies. Such investigations are essential to optimize cell expansion and differentiation and thus, potential for regenerative medicine.
Highlights
Adult stem cells are indispensable for replacing senescent cells and repairing cellular damage, especially in tissues with rapid cell turnover
To confirm adipose tissue-derived stromal cells (ADSCs) differentiation, cells from B6, BALB, and D2 were differentiated for four weeks and evaluated using histological stains; cells incubated in normal growth media for an equal period of time were used as negative controls
While no differences emerged in general cell expansion, we observed that BALB ADSCs undergo high rates of apoptosis while B6 and D2 cells do not
Summary
Adult stem cells are indispensable for replacing senescent cells and repairing cellular damage, especially in tissues with rapid cell turnover. Mesenchymal stem cells can be isolated from bone marrow and from the stromal vascular fraction (SVF) of adipose tissue; cells from the latter are termed adipose tissue-derived stromal cells (ADSCs). The intravascular location of ADSCs in adipose tissue supports the hypothesis that these cells serve as vascular precursor cells in various stages of development [4]. ADSCs exhibit standard stem cell characteristics, including selfrenewal [5] and differentiation into multiple cell types [6] of mesodermal lineages such as osteocytes [7], chondrocytes [8], and adipocytes [9]. ADSCs may differentiate into non-mesodermal cells, such as neurons [10] and hepatocytes [11]. ADSCs are obtained with minimal invasiveness and a large yield; both are significant advantages for potential clinical applications
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