Pluripotency is at the crossroads of stem cell research and biology of reproduction. The mature metaphase II oocyte contains the key factors for pluripotency induction and maintenance as assessed by its capacity to reprogram somatic nuclei. The cumulus cells (CCs) niche that surrounds the oocyte is crucial for its maturation and presumably for the oocyte to acquire its competence to confer pluripotency. In this study, we examined whether cells cultured from the human mature metaphase II oocyte CC niche (hCC) could be used as feeders for the propagation of human induced pluripotent stem cells. The induced pluripotent (iPS) cells cultured on hCC (hCC-iPS) were assessed for their pluripotency potential by their expression of pluripotency-associated genes such as Oct4, Nanog, and TRA1-60 and their competence to differentiate into the three germ layers in vitro (embryoid bodies) as well as in vivo (teratoma formation). We show that not only the hCC-iPS cells maintained their pluripotency potential, but they also exhibited much better self-renewal performance in terms of proliferation rate compared to the same cells cultured on human foreskin fibroblast (hFF) feeders (hFF-iPS). A comparative gene expression profile study of hCC and hFF revealed significant differences (P<0.05) in expression of cellular matrix components and an upregulation in hCC of genes known to be important players in cell proliferation such as interleukin 6 gene (IL6).
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References
1.
SongM, PaulS, LimH, DayemAA and ChoSG. (2012). Induced pluripotent stem cell research: a revolutionary approach to face the challenges in drug screening. Arch Pharm Res, 35:245–260.
2.
MehtaA, ChungYY, NgA, IskandarF, AtanS, WeiH, DustingG, SunW, WongP and ShimW. (2011). Pharmacological response of human cardiomyocytes derived from virus-free induced pluripotent stem cells. Cardiovasc Res, 91:577–586.
3.
HeffernanC, SumerH and VermaPJ. (2011). Generation of clinically relevant “induced pluripotent stem” (iPS) cells. J Stem Cells, 6:109–127.
4.
YoshidaY and YamanakaS. (2011). iPS cells: a source of cardiac regeneration. J Mol Cell Cardiol, 50:327–332.
5.
TakahashiK, TanabeK, OhnukiM, NaritaM, IchisakaT, TomodaK and YamanakaS. (2007). Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell, 131:861–872.
6.
YuJ, VodyanikMA, Smuga-OttoK, Antosiewicz-BourgetJ, FraneJL, TianS, NieJ, JonsdottirGA, RuottiV, et al. (2007). Induced pluripotent stem cell lines derived from human somatic cells. Science, 318:1917–1920.
7.
ParkIH, ZhaoR, WestJA, YabuuchiA, HuoH, InceTA, LerouPH, LenschMW and DaleyGQ. (2008). Reprogramming of human somatic cells to pluripotency with defined factors. Nature, 451:141–146.
8.
OkitaK, IchisakaT and YamanakaS. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448:313–317.
9.
TakahashiK and YamanakaS. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126:663–676.
10.
HalmeDG and KesslerDA. (2006). FDA regulation of stem-cell-based therapies. N Engl J Med, 355:1730–1735.
11.
MartinMJ, MuotriA, GageF and VarkiA. (2005). Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med, 11:228–232.
12.
PanC, HicksA, GuanX, ChenH and BishopCE. (2010). SNL fibroblast feeder layers support derivation and maintenance of human induced pluripotent stem cells. J Genet Genomics, 37:241–248.
13.
TakahashiK, NaritaM, YokuraM, IchisakaT and YamanakaS. (2009). Human induced pluripotent stem cells on autologous feeders. PLoS One, 4:e8067.
14.
UngerC, GaoS, CohenM, JaconiM, BergstromR, HolmF, GalanA, SanchezE, IrionO, et al. (2009). Immortalized human skin fibroblast feeder cells support growth and maintenance of both human embryonic and induced pluripotent stem cells. Hum Reprod, 24:2567–2581.
15.
LiuT, ChengW, HuangY, HuangQ, JiangL and GuoL. (2012). Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression. Exp Cell Res, 318:424–434.
16.
AnchanRM, QuaasP, Gerami-NainiB, BartakeH, GriffinA, ZhouY, DayD, EatonJL, GeorgeLL, et al. (2011). Amniocytes can serve a dual function as a source of iPS cells and feeder layers. Hum Mol Genet, 20:962–974.
17.
HavasiP, NabioniM, SoleimaniM, BakhshandehB and ParivarK. (2013). Mesenchymal stem cells as an appropriate feeder layer for prolonged in vitro culture of human induced pluripotent stem cells. Mol Biol Rep, 40:3023–3031.
18.
VuoristoS, ToivonenS, WeltnerJ, MikkolaM, UstinovJ, TrokovicR, PalgiJ, LundR, TuuriT and OtonkoskiT. (2013). A novel feeder-free culture system for human pluripotent stem cell culture and induced pluripotent stem cell derivation. PLoS One, 8:e76205.
19.
TotonchiM, TaeiA, SeifinejadA, TabebordbarM, RassouliH, FarrokhiA, GourabiH, AghdamiN, Hosseini-SalekdehG and BaharvandH. (2010). Feeder- and serum-free establishment and expansion of human induced pluripotent stem cells. Int J Dev Biol, 54:877–886.
20.
LuHF, NarayananK, LimSX, GaoS, LeongMF and WanAC. (2012). A 3D microfibrous scaffold for long-term human pluripotent stem cell self-renewal under chemically defined conditions. Biomaterials, 33:2419–2430.
21.
RodinS, DomogatskayaA, StromS, HanssonEM, ChienKR, InzunzaJ, HovattaO and TryggvasonK. (2010). Long-term self-renewal of human pluripotent stem cells on human recombinant laminin-511. Nat Biotechnol, 28:611–615.
22.
TangheS, Van SoomA, NauwynckH, CorynM and de KruifA. (2002). Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol Reprod Dev, 61:414–424.
23.
GilchristRB, LaneM and ThompsonJG. (2008). Oocyte-secreted factors: regulators of cumulus cell function and oocyte quality. Hum Reprod Update, 14:159–177.
24.
SirardMA, RichardF, BlondinP and RobertC. (2006). Contribution of the oocyte to embryo quality. Theriogenology, 65:126–136.
25.
RamirezJM, BaiQ, PequignotM, BeckerF, KassambaraA, BouinA, KalatzisV, Dijon-GrinandM and De VosJ. (2013). Side scatter intensity is highly heterogeneous in undifferentiated pluripotent stem cells and predicts clonogenic self-renewal. Stem Cells Dev, 22:1851–1860.
26.
AssouS, HaouziD, DechaudH, GalaA, FerrieresA and HamamahS. (2013). Comparative gene expression profiling in human cumulus cells according to ovarian gonadotropin treatments. Biomed Res Int, 2013:354582.
27.
BrazmaA, HingampP, QuackenbushJ, SherlockG, SpellmanP, StoeckertC, AachJ, AnsorgeW, BallCA, et al. (2001). Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat Genet, 29:365–371.
28.
TusherVG, TibshiraniR and ChuG. (2001). Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A, 98:5116–5121.
29.
EisenMB, SpellmanPT, BrownPO and BotsteinD. (1998). Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A, 95:14863–14868.
30.
FunakoshiN, DuretC, PascussiJM, BlancP, MaurelP, Daujat-ChavanieuM and Gerbal-ChaloinS. (2011). Comparison of hepatic-like cell production from human embryonic stem cells and adult liver progenitor cells: CAR transduction activates a battery of detoxification genes. Stem Cell Rev, 7:518–531.
31.
YingQL, StavridisM, GriffithsD, LiM and SmithA. (2003). Conversion of embryonic stem cells into neuroectodermal precursors in adherent monoculture. Nat Biotechnol, 21:183–186.
32.
GilbertLA and HemannMT. (2012). Context-specific roles for paracrine IL-6 in lymphomagenesis. Genes Dev, 26:1758–1768.
33.
SchwabG, SiegallCB, AardenLA, NeckersLM and NordanRP. (1991). Characterization of an interleukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266. Blood, 77:587–593.
34.
KinghamE and OreffoRO. (2013). Embryonic and induced pluripotent stem cells: understanding, creating, and exploiting the nano-niche for regenerative medicine. ACS Nano, 7:1867–1881.
35.
de PeppoGM and MaroltD. (2012). State of the art in stem cell research: human embryonic stem cells, induced pluripotent stem cells, and transdifferentiation. J Blood Transfus, 2012:317632.
36.
BenkhalifaM, DemirolA, SariT, BalashovaE, TsouroupakiM, GiakoumakisY and GurganT. (2012). Autologous embryo-cumulus cells co-culture and blastocyst transfer in repeated implantation failures: a collaborative prospective randomized study. Zygote, 20:173–180.
37.
TanXW and TanJH. (2003). [Co-culture of embryos: influencing factors and mechanisms of action]. Sheng Wu Gong Cheng Xue Bao, 19:502–505 (Article in Chinese).
38.
RuizS, PanopoulosAD, HerreriasA, BissigKD, LutzM, BerggrenWT, VermaIM and Izpisua BelmonteJC. (2011). A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity. Curr Biol, 21:45–52.
39.
PauklinS and VallierL. (2013). The cell-cycle state of stem cells determines cell fate propensity. Cell, 155:135–147.
40.
BendallSC, StewartMH, MenendezP, GeorgeD, VijayaragavanK, Werbowetski-OgilvieT, Ramos-MejiaV, RouleauA, YangJ, et al. (2007). IGF and FGF cooperatively establish the regulatory stem cell niche of pluripotent human cells in vitro. Nature, 448:1015–1021.
41.
AbrahamS, RiggsMJ, NelsonK, LeeV and RaoRR. (2010). Characterization of human fibroblast-derived extracellular matrix components for human pluripotent stem cell propagation. Acta Biomater, 6:4622–4633.
42.
ProwseAB, McQuadeLR, BryantKJ, MarcalH and GrayPP. (2007). Identification of potential pluripotency determinants for human embryonic stem cells following proteomic analysis of human and mouse fibroblast conditioned media. J Proteome Res, 6:3796–3807.
43.
LimJW and BodnarA. (2002). Proteome analysis of conditioned medium from mouse embryonic fibroblast feeder layers which support the growth of human embryonic stem cells. Proteomics, 2:1187–1203.
44.
ChinAC, FongWJ, GohLT, PhilpR, OhSK and ChooAB. (2007). Identification of proteins from feeder conditioned medium that support human embryonic stem cells. J Biotechnol, 130:320–328.
45.
MiyazakiT, FutakiS, HasegawaK, KawasakiM, SanzenN, HayashiM, KawaseE, SekiguchiK, NakatsujiN and SuemoriH. (2008). Recombinant human laminin isoforms can support the undifferentiated growth of human embryonic stem cells. Biochem Biophys Res Commun, 375:27–32.
46.
MiyazakiT, FutakiS, SuemoriH, TaniguchiY, YamadaM, KawasakiM, HayashiM, KumagaiH, NakatsujiN, SekiguchiK and KawaseE. (2012). Laminin E8 fragments support efficient adhesion and expansion of dissociated human pluripotent stem cells. Nat Commun, 3:1236.
47.
HongistoH, VuoristoS, MikhailovaA, SuuronenR, VirtanenI, OtonkoskiT and SkottmanH. (2012). Laminin-511 expression is associated with the functionality of feeder cells in human embryonic stem cell culture. Stem Cell Res, 8:97–108.
48.
VuoristoS, VirtanenI, TakkunenM, PalgiJ, KikkawaY, RousselleP, SekiguchiK, TuuriT and OtonkoskiT. (2009). Laminin isoforms in human embryonic stem cells: synthesis, receptor usage and growth support. J Cell Mol Med, 13:2622–2633.
49.
AssouS, BoumelaI, HaouziD, MonzoC, DechaudH, KadochIJ and HamamahS. (2012). Transcriptome analysis during human trophectoderm specification suggests new roles of metabolic and epigenetic genes. PLoS One, 7:e39306.
50.
BaiQ, AssouS, HaouziD, RamirezJM, MonzoC, BeckerF, Gerbal-ChaloinS, HamamahS and De VosJ. (2012). Dissecting the first transcriptional divergence during human embryonic development. Stem Cell Rev, 8:150–162.
51.
AmitM, ChebathJ, MarguletsV, LaevskyI, MiropolskyY, SharikiK, PeriM, BlaisI, SlutskyG, RevelM and Itskovitz-EldorJ. (2010). Suspension culture of undifferentiated human embryonic and induced pluripotent stem cells. Stem Cell Rev, 6:248–259.
52.
AmitM, LaevskyI, MiropolskyY, SharikiK, PeriM and Itskovitz-EldorJ. (2011). Dynamic suspension culture for scalable expansion of undifferentiated human pluripotent stem cells. Nat Protoc, 6:572–579.
53.
MaY, GuJ, LiC, WeiX, TangF, ShiG, JiangJ, KuangY, LiJ, et al. (2012). Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells. Stem Cell Res Ther, 3:29.
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