Measurement of oxygen tension within mesenchymal stem cell spheroids

Kaitlin C. Murphy, Ben P. Hung, Stephen Browne-Bourne, Dejie Zhou, Jessica Yeung, Damian C Genetos, Jonathan K Leach

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlating oxygen tension values with cell function. MSC spheroids were formed with 15 000, 30 000 or 60 000 cells per spheroid, resulting in radii of 176+8 μm, 251+12 μm and 353+18 μm, respectively. Oxygen tension values coupled with mathematical modelling revealed a gradient that varied less than 10% from the outer diameter within the largest spheroids. Despite the modest radial variance in oxygen tension, cellular metabolism from spheroids significantly decreased as the number of cells and resultant spheroid size increased. This may be due to adaptive reductions in matrix deposition and packing density with increases in spheroid diameter, enabling spheroids to avoid the formation of a hypoxic core. Overall, these data provide evidence that the enhanced function of MSC spheroids is not oxygen mediated.

Original languageEnglish (US)
Article number20160851
JournalJournal of the Royal Society Interface
Volume14
Issue number127
DOIs
StatePublished - Feb 1 2017

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Oxygen
Cellular Spheroids
Cell- and Tissue-Based Therapy
Metabolism
Cell Survival
Cell Count
Cells

Keywords

  • Diffusion
  • Hypoxia
  • Mesenchymal stem cell
  • Oxygen tension
  • Spheroid

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biophysics
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Murphy, K. C., Hung, B. P., Browne-Bourne, S., Zhou, D., Yeung, J., Genetos, D. C., & Leach, J. K. (2017). Measurement of oxygen tension within mesenchymal stem cell spheroids. Journal of the Royal Society Interface, 14(127), [20160851]. https://doi.org/10.1098/rsif.2016.0851

Measurement of oxygen tension within mesenchymal stem cell spheroids. / Murphy, Kaitlin C.; Hung, Ben P.; Browne-Bourne, Stephen; Zhou, Dejie; Yeung, Jessica; Genetos, Damian C; Leach, Jonathan K.

In: Journal of the Royal Society Interface, Vol. 14, No. 127, 20160851, 01.02.2017.

Research output: Contribution to journalArticle

Murphy, KC, Hung, BP, Browne-Bourne, S, Zhou, D, Yeung, J, Genetos, DC & Leach, JK 2017, 'Measurement of oxygen tension within mesenchymal stem cell spheroids', Journal of the Royal Society Interface, vol. 14, no. 127, 20160851. https://doi.org/10.1098/rsif.2016.0851
Murphy, Kaitlin C. ; Hung, Ben P. ; Browne-Bourne, Stephen ; Zhou, Dejie ; Yeung, Jessica ; Genetos, Damian C ; Leach, Jonathan K. / Measurement of oxygen tension within mesenchymal stem cell spheroids. In: Journal of the Royal Society Interface. 2017 ; Vol. 14, No. 127.
@article{66f5b1dbb26b4dbb86413dcf74853ef8,
title = "Measurement of oxygen tension within mesenchymal stem cell spheroids",
abstract = "Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlating oxygen tension values with cell function. MSC spheroids were formed with 15 000, 30 000 or 60 000 cells per spheroid, resulting in radii of 176+8 μm, 251+12 μm and 353+18 μm, respectively. Oxygen tension values coupled with mathematical modelling revealed a gradient that varied less than 10{\%} from the outer diameter within the largest spheroids. Despite the modest radial variance in oxygen tension, cellular metabolism from spheroids significantly decreased as the number of cells and resultant spheroid size increased. This may be due to adaptive reductions in matrix deposition and packing density with increases in spheroid diameter, enabling spheroids to avoid the formation of a hypoxic core. Overall, these data provide evidence that the enhanced function of MSC spheroids is not oxygen mediated.",
keywords = "Diffusion, Hypoxia, Mesenchymal stem cell, Oxygen tension, Spheroid",
author = "Murphy, {Kaitlin C.} and Hung, {Ben P.} and Stephen Browne-Bourne and Dejie Zhou and Jessica Yeung and Genetos, {Damian C} and Leach, {Jonathan K}",
year = "2017",
month = "2",
day = "1",
doi = "10.1098/rsif.2016.0851",
language = "English (US)",
volume = "14",
journal = "Journal of the Royal Society Interface",
issn = "1742-5689",
publisher = "Royal Society of London",
number = "127",

}

TY - JOUR

T1 - Measurement of oxygen tension within mesenchymal stem cell spheroids

AU - Murphy, Kaitlin C.

AU - Hung, Ben P.

AU - Browne-Bourne, Stephen

AU - Zhou, Dejie

AU - Yeung, Jessica

AU - Genetos, Damian C

AU - Leach, Jonathan K

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlating oxygen tension values with cell function. MSC spheroids were formed with 15 000, 30 000 or 60 000 cells per spheroid, resulting in radii of 176+8 μm, 251+12 μm and 353+18 μm, respectively. Oxygen tension values coupled with mathematical modelling revealed a gradient that varied less than 10% from the outer diameter within the largest spheroids. Despite the modest radial variance in oxygen tension, cellular metabolism from spheroids significantly decreased as the number of cells and resultant spheroid size increased. This may be due to adaptive reductions in matrix deposition and packing density with increases in spheroid diameter, enabling spheroids to avoid the formation of a hypoxic core. Overall, these data provide evidence that the enhanced function of MSC spheroids is not oxygen mediated.

AB - Spheroids formed of mesenchymal stem cells (MSCs) exhibit increased cell survival and trophic factor secretion compared with dissociated MSCs, making them therapeutically advantageous for cell therapy. Presently, there is no consensus for the mechanism of action. Many hypothesize that spheroid formation potentiates cell function by generating a hypoxic core within spheroids of sufficiently large diameters. The purpose of this study was to experimentally determine whether a hypoxic core is generated in MSC spheroids by measuring oxygen tension in aggregates of increasing diameter and correlating oxygen tension values with cell function. MSC spheroids were formed with 15 000, 30 000 or 60 000 cells per spheroid, resulting in radii of 176+8 μm, 251+12 μm and 353+18 μm, respectively. Oxygen tension values coupled with mathematical modelling revealed a gradient that varied less than 10% from the outer diameter within the largest spheroids. Despite the modest radial variance in oxygen tension, cellular metabolism from spheroids significantly decreased as the number of cells and resultant spheroid size increased. This may be due to adaptive reductions in matrix deposition and packing density with increases in spheroid diameter, enabling spheroids to avoid the formation of a hypoxic core. Overall, these data provide evidence that the enhanced function of MSC spheroids is not oxygen mediated.

KW - Diffusion

KW - Hypoxia

KW - Mesenchymal stem cell

KW - Oxygen tension

KW - Spheroid

UR - http://www.scopus.com/inward/record.url?scp=85015199619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85015199619&partnerID=8YFLogxK

U2 - 10.1098/rsif.2016.0851

DO - 10.1098/rsif.2016.0851

M3 - Article

C2 - 28179546

AN - SCOPUS:85015199619

VL - 14

JO - Journal of the Royal Society Interface

JF - Journal of the Royal Society Interface

SN - 1742-5689

IS - 127

M1 - 20160851

ER -