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Senescence and quiescence in adipose-derived stromal cells: Effects of human platelet lysate, fetal bovine serum and hypoxia

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@article{0ab6cb659bb64c2f90d499429c394b42,
title = "Senescence and quiescence in adipose-derived stromal cells: Effects of human platelet lysate, fetal bovine serum and hypoxia",
abstract = "BACKGROUND AIMS: Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent.METHODS: ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and β-galactosidase activity.RESULTS: hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions.CONCLUSION: Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions.",
keywords = "Journal Article",
author = "S{\o}ndergaard, {Rebekka Harary} and Bjarke Follin and Lund, {Lisbeth Drozd} and Morten Juhl and Annette Ekblond and Jens Kastrup and Mandana Haack-S{\o}rensen",
note = "Copyright {\circledC} 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = "1",
doi = "10.1016/j.jcyt.2016.09.006",
language = "English",
volume = "19",
pages = "95--106",
journal = "Cytotherapy",
issn = "1465-3249",
publisher = "Informa Healthcare",
number = "1",

}

RIS

TY - JOUR

T1 - Senescence and quiescence in adipose-derived stromal cells

T2 - Effects of human platelet lysate, fetal bovine serum and hypoxia

AU - Søndergaard, Rebekka Harary

AU - Follin, Bjarke

AU - Lund, Lisbeth Drozd

AU - Juhl, Morten

AU - Ekblond, Annette

AU - Kastrup, Jens

AU - Haack-Sørensen, Mandana

N1 - Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2017/1

Y1 - 2017/1

N2 - BACKGROUND AIMS: Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent.METHODS: ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and β-galactosidase activity.RESULTS: hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions.CONCLUSION: Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions.

AB - BACKGROUND AIMS: Adipose-derived stromal cells (ASCs) are attractive sources for cell-based therapies. The hypoxic niche of ASCs in vivo implies that cells will benefit from hypoxia during in vitro expansion. Human platelet lysate (hPL) enhances ASC proliferation rates, compared with fetal bovine serum (FBS) at normoxia. However, the low proliferation rates of FBS-expanded ASCs could be signs of senescence or quiescence. We aimed to determine the effects of hypoxia and hPL on the expansion of ASCs and whether FBS-expanded ASCs are senescent or quiescent.METHODS: ASCs expanded in FBS or hPL at normoxia or hypoxia until passage 7 (P7), or in FBS until P5 followed by culture in hPL until P7, were evaluated by proliferation rates, cell cycle analyses, gene expression and β-galactosidase activity.RESULTS: hPL at normoxia and hypoxia enhanced proliferation rates and expression of cyclins, and decreased G0/G1 fractions and expression of p21 and p27, compared with FBS. The shift from FBS to hPL enhanced cyclin levels, decreased p21 and p27 levels and tended to decrease G0/G1 fractions.CONCLUSION: Hypoxia does not add to the effect of hPL during ASC expansion with regard to proliferation, cell cycle regulation and expression of cyclins, p21 and p27. hPL rejuvenates FBS-expanded ASCs with regard to cell cycle regulation and expression of cyclins, p21 and p27. This indicates a reversible arrest. Therefore, we conclude that ASCs expanded until P7 are not senescent regardless of culture conditions.

KW - Journal Article

U2 - 10.1016/j.jcyt.2016.09.006

DO - 10.1016/j.jcyt.2016.09.006

M3 - Journal article

VL - 19

SP - 95

EP - 106

JO - Cytotherapy

JF - Cytotherapy

SN - 1465-3249

IS - 1

ER -

ID: 52050520