Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine

Mas-Bargues, Cristina; Sanz-Ros, Jorge; Román-Domínguez, Aurora; Inglés, Marta; Gimeno-Mallench, Lucía; Alami, Marya El; Viña-Almunia, José; Gambini, Juan; Viña, José; Borrás, Consuelo

doi:10.3390/ijms20051195

Cited by 165 publications

(134 citation statements)

References 243 publications

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“…Oxygen is one of the most important environmental factors for cells both in vivo and in vitro. It is a vital molecule serving as a metabolic substrate and a signaling mediator [218] in maintaining tissue homeostasis and supporting tissue regeneration [219,220]. Cellular adaptation to oxygen levels relies on a family of hypoxia-inducible transcription factors (HIFs) that sense changes in environmental oxygen and orchestrate a complex transcriptional program, especially HIF1 α, which is defined as the "master regulator" of hypoxia, as it is the best characterized key player in cellular response to hypoxia [221].…”

Section: Hypoxiamentioning

confidence: 99%

“…Fully mineralized bone tissue exists at a very low pO 2 , and the oxygen concentration of articular chondrocytes is less than 10% at the surface and decreases at 1% in the deepest layer [234]. Hence, the blood flow regulates the tissue oxygen pressure [235], whereby less vascularized organs receive less oxygen, and their pO 2 is significantly lowered [220].…”

Section: Hypoxiamentioning

confidence: 99%

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In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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Tendinopathy is the term used to refer to tendon disorders. Spontaneous adult tendon healing results in scar tissue formation and fibrosis with suboptimal biomechanical properties, often resulting in poor and painful mobility. The biomechanical properties of the tissue are negatively affected. Adult tendons have a limited natural healing capacity, and often respond poorly to current treatments that frequently are focused on exercise, drug delivery, and surgical procedures. Therefore, it is of great importance to identify key molecular and cellular processes involved in the progression of tendinopathies to develop effective therapeutic strategies and drive the tissue toward regeneration. To treat tendon diseases and support tendon regeneration, cell-based therapy as well as tissue engineering approaches are considered options, though none can yet be considered conclusive in their reproduction of a safe and successful long-term solution for full microarchitecture and biomechanical tissue recovery. In vitro differentiation techniques are not yet fully validated. This review aims to compare different available tendon in vitro differentiation strategies to clarify the state of art regarding the differentiation process.

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Section: Hypoxiamentioning

confidence: 99%

Section: Hypoxiamentioning

confidence: 99%

In Vitro Innovation of Tendon Tissue Engineering Strategies

Citeroni

Ciardulli

Russo

et al. 2020

IJMS

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“…Despite these studies, the role of oxygen concentration on MSC properties and therapeutic potential remain unclear, owing to differences in cell isolation methods, culture conditions and experimental strategies [25].…”

Section: Introductionmentioning

confidence: 99%

Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Rémy

Ferraro

Salver

et al. 2019

Cells

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Stem cells isolated from the apical papilla of wisdom teeth (SCAPs) are an attractive model for tissue repair due to their availability, high proliferation rate and potential to differentiate in vitro towards mesodermal and neurogenic lineages. Adult stem cells, such as SCAPs, develop in stem cell niches in which the oxygen concentration [O 2 ] is low (3-8% compared with 21% of ambient air). In this work, we evaluate the impact of low [O 2 ] on the physiology of SCAPs isolated and processed in parallel at 21% or 3% O 2 without any hyperoxic shock in ambient air during the experiment performed at 3% O 2 . We demonstrate that SCAPs display a higher proliferation capacity at 3% O 2 than in ambient air with elevated expression levels of two cell surface antigens: the alpha-6 integrin subunit (CD49f) and the embryonic stem cell marker (SSEA4). We show that the mesodermal differentiation potential of SCAPs is conserved at early passage in both [O 2 ], but is partly lost at late passage and low [O 2 ], conditions in which SCAPs proliferate efficiently without any sign of apoptosis. Unexpectedly, we show that autophagic flux is active in SCAPs irrespective of [O 2 ] and that this process remains high in cells even after prolonged exposure to 3% O 2 .

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“…Notably, hypoxia priming of MSCs induces autophagy [117], increases microvesicles and growth factors release [118,119], upregulates chemokine-receptors expression, decreases cellular senescence and apoptosis, and promotes higher retention in vivo and greater therapeutic efficacy [120]. Therefore, new strategies to improve antiviral MSC properties should be developed for production of more robust MSC-based products to treat patients with viral infection diseases, including COVID-19 [116,121,122].…”

Section: Future Directions Of Msc-based Therapies For Covid-19 and Otmentioning

confidence: 99%

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

Rocha

Oliveira

Noronha

et al. 2020

Stem Cell Rev and Rep

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Mesenchymal stromal cells (MSCs) constitute a heterogeneous population of stromal cells with immunomodulatory and regenerative properties that support their therapeutic use. MSCs isolated from many tissue sources replicate vigorously in vitro and maintain their main biological properties allowing their widespread clinical application. To date, most MSC-based preclinical and clinical trials targeted immune-mediated and inflammatory diseases. Nevertheless, MSCs have antiviral properties and have been used in the treatment of various viral infections in the last years. Here, we revised in detail the biological properties of MSCs and their preclinical and clinical applications in viral diseases, including the disease caused by the severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) infection (COVID-19). Notably, rapidly increasing numbers of MSC-based therapies for COVID-19 have recently been reported. MSCs are theoretically capable of reducing inflammation and promote lung regeneration in severe COVID-19 patients. We critically discuss the rationale, advantages and disadvantages of MSC-based therapies for viral infections and also specifically for COVID-19 and point out some directions in this field. Finally, we argue that MSC-based therapy may be a promising therapeutic strategy for severe COVID-19 and other emergent respiratory tract viral infections, beyond the viral infection diseases in which MSCs have already been clinically applied.

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Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine

Cited by 165 publications

References 243 publications

In Vitro Innovation of Tendon Tissue Engineering Strategies

In Vitro Innovation of Tendon Tissue Engineering Strategies

Isolation and Culture of Human Stem Cells from Apical Papilla under Low Oxygen Concentration Highlight Original Properties

Mesenchymal Stromal Cells in Viral Infections: Implications for COVID-19

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