Adipose tissue–derived stem cells (ASCs) are among the more attractive adult stem cell options for potential therapeutic applications. Here, we studied and compared the basic biological characteristics of ASCs isolated from humans (hASCs) and mice (mASCs) and maintained in identical culture conditions, which must be examined prior to considering further potential clinical applications. hASCs and mASCs were compared for immunophenotype, differentiation potential, cell growth characteristics, senescence, nuclear morphology, and DNA content. Although both strains of ASCs displayed a similar immunophenotype, the percentage of CD73+ cells was markedly lower and CD31+ was higher in mASC than in hASC cultures. The mean population doubling time was 98.08 ± 6.15 h for hASCs and 52.58 ± 3.74 h for mASCs. The frequency of nuclear aberrations was noticeably lower in hASCs than in mASCs regardless of the passage number. Moreover, as the cells went through several in vitro passages, mASCs showed changes in DNA content and cell cycle kinetics (frequency of hypodiploid, G0/G1, G2/M, and hyperdiploid cells), whereas all of these parameters remained constant in hASCs. Collectively, these results suggest that mASCs display higher proliferative capacity and are more unstable than hASCs in long-term cultures. These results underscore the need to consider specificities among model systems that may influence outcomes when designing potential human applications.
Get full access to this article
View all access options for this article.
References
1.
StocumDL. 2001. Stem cells in regenerative biology and medicine. Wound Repair Regen, 9:429–442.
2.
MummeryCL, DavisRP, KriegerJE. 2010. Challenges in using stem cells for cardiac repair. Sci Transl Med, 2:27ps17.
3.
TakahashiK, YamanakaS. 2006. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126:663–676.
4.
HannaJ, WernigM, MarkoulakiS, SunCW, MeissnerA, CassadyJP, BeardC, BrambrinkT, WuLC, TownesTM, JaenischR. 2007. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science, 318:1920–1923.
TholpadySS, KatzAJ, OgleRC. 2003. Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro. Anat Rec A Discov Mol Cell Evol Biol, 272:398–402.
7.
ZukPA, ZhuM, AshjianP, De UgarteDA, HuangJI, MizunoH, AlfonsoZC, FraserJK, BenhaimP, HedrickMH. 2002. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell, 13:4279–4295.
8.
HattoriH, SatoM, MasuokaK, IshiharaM, KikuchiT, MatsuiT, TakaseB, IshizukaT, KikuchiM, FujikawaK, IshiharaM. 2004. Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source. Cells Tissues Organs, 178:2–12.
9.
OgawaR, MizunoH, WatanabeA, MigitaM, ShimadaT, HyakusokuH. 2004. Osteogenic and chondrogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice. Biochem Biophys Res Commun, 313:871–877.
10.
OgawaR, MizunoH, WatanabeA, MigitaM, HyakusokuH, ShimadaT. 2004. Adipogenic differentiation by adipose-derived stem cells harvested from GFP transgenic mice-including relationship of sex differences. Biochem Biophys Res Commun, 319:511–517.
11.
EricksonGR, GimbleJM, FranklinDM, RiceHE, AwadH, GuilakF. 2002. Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun, 290:763–769.
12.
WinterA, BreitS, ParschD, BenzK, SteckE, HaunerH, WeberRM, EwerbeckV, RichterW. 2003. Cartilage-like gene expression in differentiated human stem cell spheroids: a comparison of bone marrow-derived and adipose tissue-derived stromal cells. Arthritis Rheum, 48:418–429.
13.
MizunoH, ZukPA, ZhuM, LorenzHP, BenhaimP, HedrickMH. 2002. Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr Surg, 109:199–209discussion 210–211.
14.
JeonES, ParkWS, LeeMJ, KimYM, HanJ, KimJH. 2008. A Rho kinase/myocardin-related transcription factor-A-dependent mechanism underlies the sphingosylphosphorylcholine-induced differentiation of mesenchymal stem cells into contractile smooth muscle cells. Circ Res, 103:635–642.
15.
RangappaS, FenC, LeeEH, BongsoA, SimEK. 2003. Transformation of adult mesenchymal stem cells isolated from the fatty tissue into cardiomyocytes. Ann Thorac Surg, 75:775–779.
MiranvilleA, HeeschenC, SengenesC, CuratCA, BusseR, BouloumieA. 2004. Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation, 110:349–355.
18.
Martinez-EstradaOM, Munoz-SantosY, JulveJ, ReinaM, VilaroS. 2005. Human adipose tissue as a source of Flk-1+ cells: new method of differentiation and expansion. Cardiovasc Res, 65:328–333.
19.
Planat-BenardV, SilvestreJS, CousinB, AndreM, NibbelinkM, TamaratR, ClergueM, MannevilleC, Saillan-BarreauC, DuriezM, TedguiA, LevyB, PenicaudL, CasteillaL. 2004. Plasticity of human adipose lineage cells toward endothelial cells: physiological and therapeutic perspectives. Circulation, 109:656–663.
20.
SeoMJ, SuhSY, BaeYC, JungJS. 2005. Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun, 328:258–264.
21.
KangSK, LeeDH, BaeYC, KimHK, BaikSY, JungJS. 2003. Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol, 183:355–366.
BlandeIS, BassanezeV, Lavini-RamosC, FaeKC, KalilJ, MiyakawaAA, SchettertIT, KriegerJE. 2009. Adipose tissue mesenchymal stem cell expansion in animal serum-free medium supplemented with autologous human platelet lysate. Transfusion, 49:2680–2685.
25.
BassanezeV, BaraunaVG, RamosCL, KalilJE, SchettertIT, MiyakawaAA, KriegerJE. 2010. Shear stress induces nitric oxide-mediated VEGF production in human adipose tissue mesenchymal stem cells. Stem Cells Dev, 19:371–378.
26.
WanDC, ShiYY, NacamuliRP, QuartoN, LyonsKM, LongakerMT. 2006. Osteogenic differentiation of mouse adipose-derived adult stromal cells requires retinoic acid and bone morphogenetic protein receptor type IB signaling. Proc Natl Acad Sci USA, 103:12335–12340.
27.
StenderupK, JustesenJ, ClausenC, KassemM. 2003. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone, 33:919–926.
28.
FreshneyRI. 2000. Culture of Animal Cells: A Manual of Basic Technique. Wiley-Liss: New York, NY.
29.
DimriGP, LeeX, BasileG, AcostaM, ScottG, RoskelleyC, MedranoEE, LinskensM, RubeljI, Pereira-SmithOet al. 1995. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA, 92:9363–9367.
30.
BassanezeV, MiyakawaAA, KriegerJE. 2008. A quantitative chemiluminescent method for studying replicative and stress-induced premature senescence in cell cultures. Anal Biochem, 372:198–203.
31.
BajgelmanMC, StraussBE. 2008. Development of an adenoviral vector with robust expression driven by p53. Virology, 371:8–13.
32.
PhinneyDG, KopenG, IsaacsonRL, ProckopDJ. 1999. Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth, and differentiation. J Cell Biochem, 72:570–585.
33.
JavazonEH, ColterDC, SchwarzEJ, ProckopDJ. 2001. Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. Stem Cells, 19:219–225.
34.
MalladiP, XuY, YangGP, LongakerMT. 2006. Functions of vitamin D, retinoic acid, and dexamethasone in mouse adipose-derived mesenchymal cells. Tissue Eng, 12:2031–2040.
35.
CrisostomoPR, WangM, WairiukoGM, MorrellED, TerrellAM, SeshadriP, NamUH, MeldrumDR. 2006. High passage number of stem cells adversely affects stem cell activation and myocardial protection. Shock, 26:575–580.
36.
TodaroGJ, GreenH. 1963. Quantitative studies of the growth of mouse embryo cells in culture and their development into established lines. J Cell Biol, 17:299–313.
AguilarS, NyeE, ChanJ, LoebingerM, Spencer-DeneB, FiskN, StampG, BonnetD, JanesSM. 2007. Murine but not human mesenchymal stem cells generate osteosarcoma-like lesions in the lung. Stem Cells, 25:1586–1594.
39.
RubioD, Garcia-CastroJ, MartinMC, de la FuenteR, CigudosaJC, LloydAC, BernadA. 2005. Spontaneous human adult stem cell transformation. Cancer Res, 65:3035–3039.
40.
ZhangL, HongTP, HuJ, LiuYN, WuYH, LiLS. 2005. Nestin-positive progenitor cells isolated from human fetal pancreas have phenotypic markers identical to mesenchymal stem cells. World J Gastroenterol, 11:2906–2911.
41.
LeeRH, KimB, ChoiI, KimH, ChoiHS, SuhK, BaeYC, JungJS. 2004. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem, 14:311–324.
42.
IzadpanahR, TryggC, PatelB, KriedtC, DufourJ, GimbleJM, BunnellBA. 2006. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem, 99:1285–1297.
43.
DuggalS, FrønsdalKB, SzökeK, ShahdadfarA, MelvikJE, BrinchmannJE. 2009. Phenotype and gene expression of human mesenchymal stem cells in alginate scaffolds. Tissue Eng Part A, 15:1763–1773.
44.
PengL, JiaZ, YinX, ZhangX, LiuY, ChenP, MaK, ZhouC. 2008. Comparative analysis of mesenchymal stem cells from bone marrow, cartilage, and adipose tissue. Stem Cells Dev, 17:761–773.
45.
QiaoC, XuW, ZhuW, HuJ, QianH, YinQ, JiangR, YanY, MaoF, YangH, WangX, ChenY. 2008. Human mesenchymal stem cells isolated from the umbilical cord. Cell Biol Int, 32:8–15.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
