Cell cycle regulators are critical for maintaining the differentiation potential and immaturity in adipogenesis of adipose-derived stem cells

Park, Ho; Cho, Jung Ah; Lim, Eic Ju; Lee, Chang Woo; Lee, Sang Hyuk; Seo, Sang Won; Yang, Dongyun; Lee, Kyo Won

doi:10.1016/j.diff.2011.06.002

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…Our data indicate that a greater proportion of MACS-derived ex vivo ASC exhibit activity in in vitro differentiation compared to culture-derived ASC. Increased passage number has previously been reported to result in decreased differentiation potential (Mitchell et al, 2006;Wall et al, 2007;Park et al, 2011;Lo Surdo et al, 2013). Our data extends on these previous results by including an ex vivo, uncultured, enriched population of ASC.…”

Section: Discussionsupporting

confidence: 87%

“…This method infers that large cell numbers are more clinically relevant; however, it is also likely that this period in culture will influence the functional capacity of these cells. In addition, a loss of ASC differentiation potential over time in culture has also been reported (Wall et al, 2007;Park et al, 2011;Lo Surdo et al, 2013). However, MACS enriched cells represent a more defined population that may be more potent in some settings.…”

Section: Macs Enrichment Of a Defined Population Of Asc From Svfmentioning

confidence: 95%

“…In addition, the incidence of genetic abnormalities tends to increase with time in culture (Neri et al, 2013), therefore minimizing passage number may improve the safety profile of cells. Finally, increased passage number has been reported to result in decreased potency (Wall et al, 2007;Park et al, 2011;Lo Surdo et al, 2013). To assess what effect cell culture may have at the functional and molecular level we sought to compare culture-derived ASC with an uncultured ex vivo population with a defined cell-surface phenotype based on the ISCT/IFATs recommendation (Bourin et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes

et al. 2020

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Human adipose-derived mesenchymal stromal cells (ASC) are showing clinical promise for the treatment of a range of inflammatory and degenerative conditions. These lipoaspirate-derived cells are part of the abundant and accessible source of heterogeneous stromal vascular fraction (SVF). They are typically isolated and expanded from the SVF via adherent cell culture for at least 2 weeks and as such represent a relatively undefined population of cells. We isolated ex vivo ASC directly from lipoaspirate using a cocktail of antibodies combined with immunomagnetic bead sorting. This method allowed for the rapid enrichment of a defined and untouched ex vivo ASC population (referred to as MACS-derived ASC) that were then compared to culturederived ASC. This comparison found that MACS-derived ASC contain a greater proportion of cells with activity in in vitro differentiation assays. There were also significant differences in the secretion levels of some key paracrine molecules. Moreover, when the MACS-derived ASC were subjected to adherent tissue culture, rapid changes in gene expression were observed. This indicates that culturing cells may alter the clinical utility of these cells. Although MACS-derived ASC are more defined compared to culture-derived ASC, further investigations using a comprehensive multicolor flow cytometry panel revealed that this cell population is more heterogeneous than previously appreciated. Additional studies are therefore required to more precisely delineate phenotypically distinct ASC subsets with the most therapeutic potential. This research highlights the disparity between ex vivo MACS-derived and culture-derived ASC and the need for further characterization.

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Section: Discussionsupporting

confidence: 87%

Section: Macs Enrichment Of a Defined Population Of Asc From Svfmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes

et al. 2020

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“…Our hypothesis was that changes in microRNA expression may underlie the loss of activity that was observed in in vitro differentiation assays that we and others had observed [3,[15][16][17]. The data that are presented here indicate that that is the case, as demonstrated by an over-expression of miR-378 leading to an increase in FABP4 accumulation, which is suggestive of increased differentiation down the adipogenic pathway.…”

Section: Discussionsupporting

confidence: 63%

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

Iminitoff

Damani

Williams

et al. 2020

IJMS

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There is clinical interest in using human adipose tissue-derived mesenchymal stromal cells (ASC) to treat a range of inflammatory and regenerative conditions. Aspects of ASC biology, including their regenerative potential and paracrine effect, are likely to be modulated, in part, by microRNAs, small RNA molecules that are embedded as regulators of gene-expression in most biological pathways. However, the effect of standard isolation and expansion protocols on microRNA expression in ASC is not well explored. Here, by using an untouched and enriched population of primary human ASC, we demonstrate that there are rapid and significant changes in microRNA expression when ASC are subjected to standard isolation and expansion methods. Functional studies focusing on miR-378 indicate that these changes in expression may have an impact on phenotype and function. Specifically, we found that increased levels of miR-378 significantly promoted adipogenesis in late passage ASC. These results are informative to maximizing the potential of ASC for use in various clinical applications, and they have implications for targeting microRNAs as a therapeutic strategy for obesity or metabolic disease.

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“…ADSCs exhibit standard stem cell characteristics, including self-renewal [5] and differentiation into multiple cell types [6] of mesodermal lineages such as osteocytes [7], chondrocytes [8], and adipocytes [9]. ADSCs also may differentiate into non-mesodermal cells, such as neurons [10] and hepatocytes [11].…”

Section: Introductionmentioning

confidence: 99%

Murine Adipose Tissue-Derived Stromal Cell Apoptosis and Susceptibility to Oxidative Stress In Vitro Are Regulated by Genetic Background

Pazdro

Harrison

2013

PLoS ONE

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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.

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Cell cycle regulators are critical for maintaining the differentiation potential and immaturity in adipogenesis of adipose-derived stem cells

Cited by 22 publications

References 30 publications

Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes

Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Are a Heterogeneous Population That Demonstrate Rapid Culture-Induced Changes

microRNAs in Ex Vivo Human Adipose Tissue Derived Mesenchymal Stromal Cells (ASC) Undergo Rapid Culture-Induced Changes in Expression, Including miR-378 which Promotes Adipogenesis

Murine Adipose Tissue-Derived Stromal Cell Apoptosis and Susceptibility to Oxidative Stress In Vitro Are Regulated by Genetic Background

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