Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic differentiation

Krinner, Axel; Zscharnack, Matthias; Bader, Augustinus; Drasdo, Dirk; Galle, Joerg

doi:10.1111/j.1365-2184.2009.00621.x

Cited by 80 publications

(71 citation statements)

References 48 publications

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“…The cells were cultured up to a density A positive effect of hypoxic conditions on the proliferation rate and maintenance of the undifferentiated state was described in several publications [9][10][11][12][13]. Additionally it could be shown that mesenchymal stem cells, which had been cultured under hypoxic conditions (2 -5% oxygen in the aeration gas) showed a better differentiation potential when transferred to normoxic conditions [10,11].…”

Section: Resultsmentioning

confidence: 99%

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

Weber¹,

Freimark²,

Pörtner

et al. 2010

Int J Artif Organs

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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.

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Section: Resultsmentioning

confidence: 99%

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

Weber¹,

Freimark²,

Pörtner

et al. 2010

Int J Artif Organs

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“…Enhanced proliferation has previously been reported for MSCs maintained at a low oxygen tension. [57][58][59][60] This proliferative potential during monolayer expansion was maintained during chondrogenic differentiation, both in pellet culture, but also in hydrogel culture once FPSCs were stimulated with serum. FPSCs did not appear to proliferate within the hydrogel, but rather on the construct surface.…”

Section: Discussionmentioning

confidence: 99%

The Role of Environmental Factors in Regulating the Development of Cartilaginous Grafts Engineered Using Osteoarthritic Human Infrapatellar Fat Pad–Derived Stem Cells

Liu

Buckley

Downey

et al. 2012

Tissue Engineering Part A

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“…Within the niche of many adult stem cells, oxygen levels are usually much lower than those in the ambient air or even in the host tissue (Simon and Keith, 2008;Simsek et al, 2010). For instance, oxygen levels in the niches of mesenchymal, hematopoietic and neural stem cells are 2-8%, 1-6% and 1-8%, respectively (Clarke and van der Kooy, 2009;Eliasson and Jonsson, 2010;Krinner et al, 2009;Mohyeldin et al, 2010). Low oxygen tension (hypoxia) is critical for multiple stem cells to maintain their stemness and the hypoxia niche plays a crucial role in the self-renewal and proliferation of the resident stem cells.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes satellite cell self-renewal and enhances the efficiency of myoblast transplantation

et al. 2012

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SUMMARYMicroenvironmental oxygen (O 2 ) regulates stem cell activity, and a hypoxic niche with low oxygen levels has been reported in multiple stem cell types. Satellite cells are muscle-resident stem cells that maintain the homeostasis and mediate the regeneration of skeletal muscles. We demonstrate here that hypoxic culture conditions favor the quiescence of satellite cell-derived primary myoblasts by upregulating Pax7, a key regulator of satellite cell self-renewal, and downregulating MyoD and myogenin. During myoblast division, hypoxia promotes asymmetric self-renewal divisions and inhibits asymmetric differentiation divisions without affecting the overall rate of proliferation. Mechanistic studies reveal that hypoxia activates the Notch signaling pathway, which subsequently represses the expression of miR-1 and miR-206 through canonical Hes/Hey proteins, leading to increased levels of Pax7. More importantly, hypoxia conditioning enhances the efficiency of myoblast transplantation and the self-renewal of implanted cells. Given the robust effects of hypoxia on maintaining the quiescence and promoting the self-renewal of cultured myoblasts, we predict that oxygen levels in the satellite cell niche play a central role in precisely balancing quiescence versus activation, and self-renewal versus differentiation, in muscle stem cells in vivo.

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Impact of oxygen environment on mesenchymal stem cell expansion and chondrogenic differentiation

Cited by 80 publications

References 48 publications

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

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

The Role of Environmental Factors in Regulating the Development of Cartilaginous Grafts Engineered Using Osteoarthritic Human Infrapatellar Fat Pad–Derived Stem Cells

Hypoxia promotes satellite cell self-renewal and enhances the efficiency of myoblast transplantation

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