Abstract
Hyaluronan-coated surfaces preserve the proliferation and differentiation potential of mesenchymal stem cells by prolonging their G1-phase transit, which maintains cells in a slow-proliferative mode. Mitochondria are known to play a crucial role in stem cell self-renewal and differentiation. In this study, for the first time, the metabolic mechanism underlying the hyaluronan-regulated slow-proliferative maintenance of stem cells was investigated by evaluating mitochondrial functions. Human placenta-derived mesenchymal stem cells (PDMSCs) cultured on hyaluronan-coated surfaces at 0.5, 3.0, 5.0, and 30 µg/cm 2 were found to have an average 58% higher mitochondrial mass and an increase in mitochondrial DNA copy number compared to noncoated tissue culture surfaces (control), as well as a threefold increase in the gene expression of the mitochondrial biogenesis-related gene PGC-1α. Increase in mitochondrial biogenesis led to a hyaluronan dose-dependent increase in mitochondrial membrane potential, ATP content, and oxygen consumption rate, with reactive oxygen species levels shown to be at least three times lower compared to the control. Although hyaluronan seemed to favor mitochondrial function, cell entry into a hyaluronan-regulated slow-proliferative mode led to a fivefold reduction in ATP production and coupling efficiency levels. Together, these results suggest that hyaluronan-coated surfaces influence the metabolic proliferative state of stem cells by upregulating mitochondrial biogenesis and function with controlled ATP production. This more efficiently meets the energy requirements of slow-proliferating PDMSCs. A clear understanding of the metabolic mechanism induced by hyaluronan in stem cells will allow future applications that may overcome the current limitations faced in stem cell culture. Stem Cells 2016;34:2512–2524.
| Original language | English |
|---|---|
| Pages (from-to) | 2512-2524 |
| Number of pages | 13 |
| Journal | Stem Cells |
| Volume | 34 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2016 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Developmental Biology
- Cell Biology
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Hyaluronan Upregulates Mitochondrial Biogenesis and Reduces Adenoside Triphosphate Production for Efficient Mitochondrial Function in Slow-Proliferating Human Mesenchymal Stem Cells. / Solis, Mairim Alexandra; Wei, Yau Huei; Chang, Chiung-Hsin; Yu, Chen-Hsiang; Kuo, Pao-Lin; Huang, Lynn Ling-Huei.
In: Stem Cells, Vol. 34, No. 10, 01.10.2016, p. 2512-2524.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hyaluronan Upregulates Mitochondrial Biogenesis and Reduces Adenoside Triphosphate Production for Efficient Mitochondrial Function in Slow-Proliferating Human Mesenchymal Stem Cells
AU - Solis, Mairim Alexandra
AU - Wei, Yau Huei
AU - Chang, Chiung-Hsin
AU - Yu, Chen-Hsiang
AU - Kuo, Pao-Lin
AU - Huang, Lynn Ling-Huei
PY - 2016/10/1
Y1 - 2016/10/1
N2 - Hyaluronan-coated surfaces preserve the proliferation and differentiation potential of mesenchymal stem cells by prolonging their G1-phase transit, which maintains cells in a slow-proliferative mode. Mitochondria are known to play a crucial role in stem cell self-renewal and differentiation. In this study, for the first time, the metabolic mechanism underlying the hyaluronan-regulated slow-proliferative maintenance of stem cells was investigated by evaluating mitochondrial functions. Human placenta-derived mesenchymal stem cells (PDMSCs) cultured on hyaluronan-coated surfaces at 0.5, 3.0, 5.0, and 30 µg/cm 2 were found to have an average 58% higher mitochondrial mass and an increase in mitochondrial DNA copy number compared to noncoated tissue culture surfaces (control), as well as a threefold increase in the gene expression of the mitochondrial biogenesis-related gene PGC-1α. Increase in mitochondrial biogenesis led to a hyaluronan dose-dependent increase in mitochondrial membrane potential, ATP content, and oxygen consumption rate, with reactive oxygen species levels shown to be at least three times lower compared to the control. Although hyaluronan seemed to favor mitochondrial function, cell entry into a hyaluronan-regulated slow-proliferative mode led to a fivefold reduction in ATP production and coupling efficiency levels. Together, these results suggest that hyaluronan-coated surfaces influence the metabolic proliferative state of stem cells by upregulating mitochondrial biogenesis and function with controlled ATP production. This more efficiently meets the energy requirements of slow-proliferating PDMSCs. A clear understanding of the metabolic mechanism induced by hyaluronan in stem cells will allow future applications that may overcome the current limitations faced in stem cell culture. Stem Cells 2016;34:2512–2524.
AB - Hyaluronan-coated surfaces preserve the proliferation and differentiation potential of mesenchymal stem cells by prolonging their G1-phase transit, which maintains cells in a slow-proliferative mode. Mitochondria are known to play a crucial role in stem cell self-renewal and differentiation. In this study, for the first time, the metabolic mechanism underlying the hyaluronan-regulated slow-proliferative maintenance of stem cells was investigated by evaluating mitochondrial functions. Human placenta-derived mesenchymal stem cells (PDMSCs) cultured on hyaluronan-coated surfaces at 0.5, 3.0, 5.0, and 30 µg/cm 2 were found to have an average 58% higher mitochondrial mass and an increase in mitochondrial DNA copy number compared to noncoated tissue culture surfaces (control), as well as a threefold increase in the gene expression of the mitochondrial biogenesis-related gene PGC-1α. Increase in mitochondrial biogenesis led to a hyaluronan dose-dependent increase in mitochondrial membrane potential, ATP content, and oxygen consumption rate, with reactive oxygen species levels shown to be at least three times lower compared to the control. Although hyaluronan seemed to favor mitochondrial function, cell entry into a hyaluronan-regulated slow-proliferative mode led to a fivefold reduction in ATP production and coupling efficiency levels. Together, these results suggest that hyaluronan-coated surfaces influence the metabolic proliferative state of stem cells by upregulating mitochondrial biogenesis and function with controlled ATP production. This more efficiently meets the energy requirements of slow-proliferating PDMSCs. A clear understanding of the metabolic mechanism induced by hyaluronan in stem cells will allow future applications that may overcome the current limitations faced in stem cell culture. Stem Cells 2016;34:2512–2524.
UR - http://www.scopus.com/inward/record.url?scp=84990871946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84990871946&partnerID=8YFLogxK
U2 - 10.1002/stem.2404
DO - 10.1002/stem.2404
M3 - Article
C2 - 27354288
AN - SCOPUS:84990871946
VL - 34
SP - 2512
EP - 2524
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 10
ER -