Expansion of Human Mesenchymal Stem Cells in a Fixed-Bed Bioreactor System Based on Non-Porous Glass Carrier – Part B: Modeling and Scale-up of the System
Restricted accessResearch articleFirst published online 2010
Expansion of Human Mesenchymal Stem Cells in a Fixed-Bed Bioreactor System Based on Non-Porous Glass Carrier – Part B: Modeling and Scale-up of the System
Human mesenchymal stem cells (hMSC) are a promising cell source for the manufacturing of cell therapy or tissue-engineered implants. In part A of this publication a fixed-bed bioreactor system based on non-porous borosilicate glass spheres and procedures for the automated expansion of hMSC with high yield and vitality was introduced. Part B of this study deals with the modeling of the process in order to transfer the bioreactor system from the laboratory to the production scale. Relevant model parameters were obtained by fitting them to the experimental data of hMSC-TERT cultivations in scales up to 300 cm3. Scale-up calculations were carried out exemplarily for a target cell number of twenty billion cells.
VijaaL, FargecD, GautierbJF, Mesenchymal stem cells: Stem cell therapy perspectives for type 1 diabetes.Diabetes Metab2009; 35: 85–93.
3.
WeberC, FreimarkD, PoertnerR, Pino-GraceP, PohlS, WallrappC, GeigleP, CzermakP.Expansion of human mesenchymal stem cells in a fixed-bed bioreactors system - Part A: Inoculation, cultivation, and harvesting procedures.Int J Artif Organs2010; 33; 512–25.
4.
WeberC, PohlS, PoertnerR, Production process for stem cell-based therapeutic implants - Expansion of the production cell line and cultivation of encapsulated cells. In:. In: KasperC, van GriensvenM, PoertnerR, eds. Advances in Biochemical Engineering/Biotechnology.Berlin: Springer; 2010 (in press).
5.
SimonsenJL, RosadaC, SerakinciN, Telomerase expression extends the proliferative life-span and maintains the osteogenic potential of human bone marrow stromal cells.Nat Biotechnol2002; 20: 592–6.
6.
WeberC, PohlS, PörtnerR, Cultivation and differentiation of encapsulated hMSC-TERT in a disposable small-scale syringe-like fixed bed reactor.Open Biomed Eng J2007;1: 64–70.
7.
HigueraG, SchopD, JanssenF, van Dijkhuizen-RadersmaR, van BoxtelT, van BlitterswijkCA.Quantifying in vitro growth and metabolism kinetics of human mesenchymal stem cells using a mathematical model.Tissue Eng Part A2009; 15: 2653–63.
8.
KarabelasAJ, WegnerTH, HanrattyTJ.Use of asymptotic relations to correlate mass transfer data in packed beds.Chem Eng Sci1971; 26: 1581–9.
9.
HungSC, PochampallyRR, HsuSC, Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo.PLoS ONE2007; 2: e416.
10.
FehrerC, BrunauerR, LaschoberG, UnterluggauerH, ReitingerS, KlossF.Reduced oxygen tension attenuates differentiation capacity of human mesenchymal stem cells and prolongs their lifespan.Aging Cell2007; 6: 745–57.
11.
KrinnerA, ZscharnackM, BaderA, DrasdoD, GalleJ.Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic differentiation.Cell Prolif2009; 42: 471–84.
12.
GraysonWL, ZhaoF, IzadpanahR, BunnellB, MaT.Effects of hypoxia on human mesenchymal stem cell expansion and plasticity in 3D constructs.J Cell Physiol2006; 207: 331–9.
13.
MaT, GraysonWL, FröhlichM, Vunjak-NovakovicG.Hypoxia and stem cell-based engineering of mesenchymal tissues.Biotechnol Prog2009; 25: 32–42.
14.
WeberC, GokorschS, CzermakP.Expansion and chondrogenic differentiation of human mesenchymal stem cells.Int J Artif Organs2007; 30: 611–8.
15.
WeberC, PohlS, PörtnerR, Expansion and harvesting of hMSC-TERT.Open Biomed Eng J2007; 1: 38–46.
16.
PörtnerR, KoopM.A model for oxygen supply in fixed bed reactors with immobilized hybridoma cells.Bioprocess Biosyst Eng1997; 17: 269–75.
17.
VenâncioA, TeixeiraJA.Characterization of sugar diffusion coefficients in alginate membranes.Biotechnol Tech1997; 11: 183–6.
18.
WeastRC.CRC handbook of chemistry and physics.Clermont, Florida: CRC Press, 1978.
19.
CroughanMS, SayreES, WangDI.Viscous reduction of turbulent damage in animal cell culture.Biotechnol Bioeng1988; 33: 862–72.
20.
LonerganT, BrennerC, BavisterB.Differentiation-related changes in mitochondrial properties as indicators of stem cell competence.J Cell Physiol2006; 208: 149–53.
21.
CongetPA, MinguellJJ.Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells.J Cell Physiol1999; 181: 67–73.
22.
GuoZ, YangJ, LiuX, Biological features of mesenchymal stem cells from human bone marrow.Chin Med J (Engl)2001; 114: 950–3.
23.
LiuY-H, BiJ-X, ZengA-P, YuanJ-Q.A simple kinetic model for myeloma cell culture with consideration of lysine limitation.Bioprocess Biosyst Eng2008; 31: 569–77.
24.
SoukupT, MokrýJ, KarbanováJ, PytlíkR, SuchomelP, KučerováL.Mesenchymal stem cells isolated from human bone marrow: cultivation, phenotypic analysis and changes in proliferation kinetics.Acta Med (Hradec Kralove)2006; 49: 27–33.
25.
AmitM, CarpenterMK, InokumaMS, ChiuC P, ThomsonJA.Clonally derived human embryonic stem cell lines maintain pluripotency and proliferative potential for prolonged periods of pulture.Dev Biol2000; 227: 271–8.
26.
AbranchesE, BekmanE, HenriqueD, CabralJM.Expansion of mouse embryonic stem cells on microcarriers.Biotechnol Bioeng2006; 96: 1211–21.
27.
BreguetV, GugerliRI, von StockarU, MarisonIW.CHO immobilization in alginate/poly-L-lysine microcapsules: an understanding of potential and limitations.Cytotechnology2007; 53: 81–93.
28.
ShiraiY, HashimotoK, TakamatsuH.Growth kinetics of Hybridoma cells in high density culture.J Ferment Bioeng1992; 73: 159–65.
29.
SchopD, JanssenFW, BorgartE, de BruijnJD, van Dijkhuizen-RadersmaR.Expansion of mesenchymal stem cells using a microcarrier-based cultivation system: growth and metabolism.J Tissue Eng Regen Med2008; 2: 126–35.
30.
BorenJ, CascanteM, MarinS, Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells.J Biol Chem2001; 276: 37747–53.
31.
FrahmB, LaneP, AtzertH, Adaptive, model-based control by the open-loop-feedback-optimal (OLFO) controller for the effective fed-batch cultivation of hybridoma cells.Biotechnol Prog2002; 18: 1095–103.
32.
LubinieckiAS.Large-scale mammalian cell culture technology.New York, NY: Marcel Dekker; 1990.
33.
PengCA, PalsonBA.Determination of specific oxygen uptake rates in human hematopoietic cultures and implications for bioreactor design.Ann Biomed Eng1996; 24: 373–81.
34.
AcevedoCA, Weinstein-OppenheimerC, BrownDI, HuebnerH, BuchholzR, YoungME.A mathematical model for the design of fibrin microcapsules with skin cells.Bioprocess Biosyst Eng2008; 32: 341–51.
35.
De LeònA, MayaniH, RamırezOT.Design, characterization and application of a minibioreactor for the culture of human hematopoietic cells under controlled conditions.Cytotechnology1998; 28: 127–38.
36.
YounBS, SenA, BehieLA.Scale-up of breast cancer stem cell aggregate cultures to suspension bioreactors.Biotechnol Prog2006; 22: 801–10.
