The Role of Mitochondria in Stem Cell Biology

Nesti, Claudia; Pasquali, Livia; Vaglini, Francesca; Siciliano, Gabriele; Murri, Luigi

doi:10.1007/s10540-007-9044-1

Cited by 58 publications

(34 citation statements)

References 39 publications

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“…Our study confirms and provides more detailed evidences for the suggestion of other authors that stemness may be estimated using certain functional mitochondrial characteristics [8], indicating that along with the numerous changes in cell infrastructure, including the redistribution of mitochondria, an increase in the unusually low mitochondrial NADH content may serve for the noninvasive fluorescence measurement based monitoring of the development of complex differentiation processes. Thus, we suggest that an increase in NAD(P)H fluorescence may be useful for a non-invasive detection of the onset of myoblast differentiation.…”

Section: Resultssupporting

confidence: 87%

“…Recently, some authors have suggested a hypothesis that stem cell competence (i. e. stem cell stability and pluripotency) may be estimated using functional mitochondrial characteristics [8]. Lonergan et al [2] found that several mitochondrial properties, such as subcellular localization and metabolic activity, can be considered as markers of "stemness".…”

Section: Resultsmentioning

confidence: 99%

“…The lar gest myoblasts were observed on the 10th day of differentiation when the mean size of the population was 406 µm 2 (250-450 µm 2 cells made 62% and 600-800 µm 2 cells 14%). After 12 days of differentiation, Fr3 myoblasts became oblong-shaped and started reducing in size (150-300 µm 2 cells made 50% of population); their viability also slightly reduced.Recently, some authors have suggested a hypothesis that stem cell competence (i. e. stem cell stability and pluripotency) may be estimated using functional mitochondrial characteristics [8]. Lonergan et al [2] found that several mitochondrial properties, such as subcellular localization and metabolic activity, can be considered as markers of "stemness".…”

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confidence: 99%

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Differentiation-related changes in myogenic stem cells

Degutytė-Fomins¹,

Žūkienė²,

Buzaitė³

et al. 2010

Biologija

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Skeletal myoblast cells have a high potential for cell therapy based repair of the injured myocardium. Stem cell differentiation markers are important for finding an appropriate cellular state optimal for engraftment. We followed differentiation-induced changes in cellular size, the distribution of mitochondria, adenine and pyridine nucleotide content, NAD(P)H fluorescence in skeletal myogenic stem cell populations derived from rabbit skeletal muscle. The fraction of larger size cells increased during differentiation. Mitochondrial distribution changed from perinuclear in undifferentiated cells to even in the cytoplasm of differentiated cells. The most remarkable feature of undifferentiated myoblasts was a very low NAD(P)H fluorescence which augmented after initiating cell differentiation, due to metabolic and physiological changes, but that did not correlate with an increase in cellular size. A significant increase of NAD(P)H concentration was chromatographically detected after 8 days of differentiation, although the NAD(P)H fluorescence increased by 42% as soon as after three days and 2.7-fold after five days of differentiation as compared with the control. We show that the early increase in fluorescence is determined by mitochondrial NADH, but upon a longer differentiation NADPH amount also increases. The total amount of adenine nucleotides (ATP, ADP, AMP) increased, but the ATP / ADP ratio decreased during differentiation. We suggest that an increase in NAD(P)H fluorescence may be useful for a non-invasive detection of the onset and course of myoblast differentiation. INtRODuctIONThe high therapeutical potential of skeletal myoblasts makes important a thorough understanding of cell differentiation process. The changes stem cells undergo during differentiation include transformations of cell shape, ultrastructure, biochemical composition and metabolism. The goal to employ cells for regenerative medicine implies the necessity of knowing how to track and control the differentiation process. Noninvasive and rapid methods to monitor the metabolic and viability state in differentiating cells are under extreme request. The pyridine dinucleotides NAD + / NADH and NADP + / NADPH are important indicators of cell viability and energy metabolism state. Taking into account that their reduced forms are natural cellular fluorophores, it is reasonable to verify how NAD(P)H fluorescence correlates with numerous changes in cell state during differentiation. This should help to estimate to what extent NAD(P)H fluorescence measurements may be useful for a noninvasive analysis.When a cell enters the differentiation process, it switches the metabolism from anaerobic to aerobic [1]. The expression of mitochondrial enzymes and the respiration rate increase and the mitochondrial distribution changes from perinuclear to even in the cell volume [2]. Although several authors have focused on changes in adenine nucleotides [1,2], the content of pyridine dinucleotides in stem cells and their changes during differentiation have not yet been...

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Differentiation-related changes in myogenic stem cells

Degutytė-Fomins¹,

Žūkienė²,

Buzaitė³

et al. 2010

Biologija

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“…However, information is sparse concerning how exactly CD44 may affect mitochondrial function. Stem cell mitochondria have recently come under increased scrutiny because new information has revealed their role in numerous cellular processes, beyond ATP production and apoptosis regulation, suggesting mitochondria to serve as a cell fate or lineage determinant [50–52]. Thus, hyaluronan influence on mitochondrial properties may at least to some extent affect stem cell self-renewal and differentiation.…”

Section: Influence Of Hyaluronan On Stem Cell Behaviormentioning

confidence: 99%

Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells

Solís

Chen

Wong

et al. 2012

Biochemistry Research International

176

114

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Hyaluronan is a linear glycosaminoglycan that has received special attention in the last few decades due to its extraordinary physiological functions. This highly viscous polysaccharide is not only a lubricator, but also a significant regulator of cellular behaviors during embryogenesis, morphogenesis, migration, proliferation, and drug resistance in many cell types, including stem cells. Most hyaluronan functions require binding to its cellular receptors CD44, LYVE-1, HARE, layilin, and RHAMM. After binding, proteins are recruited and messages are sent to alter cellular activities. When low concentrations of hyaluronan are applied to stem cells, the proliferative activity is enhanced. However, at high concentrations, stem cells acquire a dormant state and induce a multidrug resistance phenotype. Due to the influence of hyaluronan on cells and tissue morphogenesis, with regards to cardiogenesis, chondrogenesis, osteogenesis, and neurogenesis, it is now been utilized as a biomaterial for tissue regeneration. This paper summarizes the most important and recent findings regarding the regulation of hyaluronan in cells.

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“…Beside their well-known function in energy supply, mitochondria play pivotal roles in other essential cellular processes, such as the formation of Fe-S-clusters, calcium homeostasis, oxygen sensing, cellular proliferation, apoptosis and aging [1]. By now it is becoming evident that mitochondria are also important for cell differentiation processes [2], [3], [4].…”

Section: Introductionmentioning

confidence: 99%

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

et al. 2012

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Mitochondria are essential organelles with multiple functions, especially in energy metabolism. Recently, an increasing number of data has highlighted the role of mitochondria for cellular differentiation processes. Metabolic differences between stem cells and mature derivatives require an adaptation of mitochondrial function during differentiation. In this study we investigated alterations of the mitochondrial phenotype of human mesenchymal stem cells undergoing adipogenic differentiation. Maturation of adipocytes is accompanied by mitochondrial biogenesis and an increase of oxidative metabolism. Adaptation of the mt phenotype during differentiation is reflected by changes in the distribution of the mitochondrial network as well as marked alterations of gene expression and organization of the oxidative phosphorylation system (OXPHOS). Distinct differences in the supramolecular organization forms of cytochrome c oxidase (COX) were detected using 2D blue native (BN)-PAGE analysis. Most remarkably we observed a significant increase in the abundance of OXPHOS supercomplexes in mitochondria, emphasizing the change of the mitochondrial phenotype during adipogenic differentiation.

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The Role of Mitochondria in Stem Cell Biology

Abstract: This mini-review summarizes the current literature on the role of mitochondrial DNA mutations and mitochondrial metabolism in stem cell biology. The possible uses of stem cells as a therapeutic tool in mitochondrial disorders are also reported.

Cited by 58 publications

References 39 publications

Differentiation-related changes in myogenic stem cells

Differentiation-related changes in myogenic stem cells

Hyaluronan Regulates Cell Behavior: A Potential Niche Matrix for Stem Cells

OXPHOS Supercomplexes as a Hallmark of the Mitochondrial Phenotype of Adipogenic Differentiated Human MSCs

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