Journal ArticleDOI
The metabolism of human mesenchymal stem cells during proliferation and differentiation
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TLDR
Osteogenic and chondrogenic MSC cultures appear to adopt the balance of oxidative phosphorylation and glycolysis reported for the respective mature cell phenotypes.Abstract:
Human mesenchymal stem cells (MSCs) reside under hypoxic conditions in vivo, between 4% and 7% oxygen. Differentiation of MSCs under hypoxic conditions results in inhibited osteogenesis, while chondrogenesis is unaffected. The reasons for these results may be associated with the inherent metabolism of the cells. The present investigation measured the oxygen consumption, glucose consumption and lactate production of MSCs during proliferation and subsequent differentiation towards the osteogenic and chondrogenic lineages. MSCs expanded under normoxia had an oxygen consumption rate of ∼98 fmol/cell/h, 75% of which was azide-sensitive, suggesting that these cells derive a significant proportion of ATP from oxidative phosphorylation in addition to glycolysis. By contrast, MSCs differentiated towards the chondrogenic lineage using pellet culture had significantly reduced oxygen consumption after 24 h in culture, falling to ∼12 fmol/cell/h after 21 days, indicating a shift towards a predominantly glycolytic metabolism. By comparison, MSCs retained an oxygen consumption rate of ∼98 fmol/cell/h over 21 days of osteogenic culture conditions, indicating that these cells had a more oxidative energy metabolism than the chondrogenic cultures. In conclusion, osteogenic and chondrogenic MSC cultures appear to adopt the balance of oxidative phosphorylation and glycolysis reported for the respective mature cell phenotypes. The addition of TGF-β to chondrogenic pellet cultures significantly enhanced glycosaminoglycan accumulation, but caused no significant effect on cellular oxygen consumption. Thus, the differences between the energy metabolism of chondrogenic and osteogenic cultures may be associated with the culture conditions and not necessarily their respective differentiation.read more
Citations
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Journal ArticleDOI
Metabolic requirements for the maintenance of self-renewing stem cells
Keisuke Ito,Toshio Suda +1 more
TL;DR: Investigation into the molecular mechanisms and metabolic pathways underlying stem cell self-renewal and differentiation hold great therapeutic promise.
Journal ArticleDOI
Stem cell metabolism in tissue development and aging
TL;DR: Recent studies of metabolism in stem cells that have revealed a shift in the balance between glycolysis, mitochondrial oxidative phosphorylation and oxidative stress during the maturation of adult stem cells, and during the reprogramming of somatic cells to pluripotency are reviewed.
Journal ArticleDOI
High Mesenchymal Stem Cell Seeding Densities in Hyaluronic Acid Hydrogels Produce Engineered Cartilage with Native Tissue Properties
Isaac E. Erickson,Sydney R. Kestle,Kilief H. Zellars,Megan J. Farrell,Minwook Kim,Jason A. Burdick,Robert L. Mauck +6 more
TL;DR: These findings with a novel photocrosslinked hyaluronic acid (HA) hydrogel suggest that stiff gels (high HA concentration, 5% w/v) foster chondrogenic differentiation and matrix production, but limit overall functional maturation due to the inability of the formed matrix to diffuse away from the point of production and form a contiguous network.
Journal ArticleDOI
Energy Metabolism in Mesenchymal Stem Cells During Osteogenic Differentiation.
TL;DR: Using bioenergetic profiling and transcriptomics, it is established that MSCs activate the mitochondrial process of oxidative phosphorylation (OxPhos) during osteogenic differentiation, but they maintain levels of glycolysis similar to undifferentiated cells, and a HIF-based mechanism of regulation of mitochondrial OxPhos is proposed.
Journal ArticleDOI
Mechanisms Underlying the Osteo- and Adipo-Differentiation of Human Mesenchymal Stem Cells
TL;DR: The current findings for adipo- and osteo-differentiation are summarized together with a brief statement on first clinical trials.
References
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Mark F. Pittenger,Alastair Morgan Mackay,Stephen C. Beck,Rama K. Jaiswal,Robin Douglas,Joseph D. Mosca,Mark Aaron Moorman,Donald William Jr. Ward Road Simonetti,Stewart Craig,Daniel R. Marshak +9 more
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Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue
TL;DR: A modified form of the dim methylmethylene blue assay is described that has improved specificity for sulphated glycosaminoglycans, and it is shown that in conjunction with specific polysaccharidases, the dimethylmethyleneblue assay can be used to quantitate individual sulphated sugarcans.
Journal ArticleDOI
Mesenchymal stem cells: building blocks for molecular medicine in the 21st century
Arnold I. Caplan,Scott P. Bruder +1 more
TL;DR: By understanding the complex, multistep and multifactorial differentiation pathway from MSC to functional tissues, it might be possible to manipulate MSCs directly in vivo to cue the formation of elaborate, composite tissues in situ.
Journal ArticleDOI
Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model
TL;DR: The data suggest a possible model of predetermined bone marrow stromal cells differentiation where the tripotent cells can be considered as early mesenchymal progenitor that display a sequential loss of lineage potentials, generating osteochondrogenic progenitors which, in turn, give rise to osteogenic precursors.
Book
Biochemistry for the Medical Sciences
Eric A. Newsholme,A. R. Leech +1 more
TL;DR: This outstanding text, written in a clear, concise and easy-to-read style, provides students with an in-depth explanation of how each metabolic pathway is directly related to physiology, pharmacology, and clinical medicine.