Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

Kwon, Se Yun; Chun, So Young; Ha, Yun Sok; Kim, Dae Hwan; Kim, Jeongshik; Song, Phil Hyun; Kim, Hyun Tae; Yoo, Eun Sang; Kim, Bum Soo; Kwon, Tae Gyun

doi:10.1007/s13770-017-0068-8

Cited by 92 publications

(74 citation statements)

References 33 publications

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“…Different stem cell markers and early mesodermal/endothelial genes showed an increased expression in hypoxia, indicating that culturing WJ-MSCs in hypoxia leads to different development results or the commission to different cells 32 . The influence of hypoxia on the differentiation potential of MSCs is an intriguing argument, and the literature is divided on the subject, with some studies showing an inhibition of differentiation capacity 36,37 , while others indicate a better differentiation capacity of MSCs under hypoxic conditions 16,38 . Cicione et al showed that severe hypoxia reduced the differentiation capacity of bone marrow MSCs (BMSCs) toward the adipogenic, osteogenic, and chondrogenic lineage 36 .…”

Section: Discussionmentioning

confidence: 99%

“…It has already been shown that hypoxia may improve the immunomodulatory activity of GMSCs, increase skin wound repair in vivo, and promote the regenerative properties of GMSCs, suggesting that hypoxic preconditioning may be a good method to optimize the potential of GMSCs for tissue regeneration and stem cell therapies 15 . In addition, MSCs cultured under hypoxia (5% O 2 for 5 days) presented a higher proliferation rate, maintained higher levels of MSC surface markers, and expressed increased levels of Oct4, C-Myc, Nanog, nestin, and HIF-1a compared with cells under normoxic conditions 16 . However, whether hypoxia can ameliorate the differentiation potential of MSCs is still under debate, and contrasting results have been reported.…”

Section: Introductionmentioning

confidence: 94%

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The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study

et al. 2019

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Mesenchymal stem cells (MSCs) are widely used in stem cell therapy for regenerative purposes. Oral-derived MSCs, such as gingival MSCs (GMSCs), deriving from the neural crest seem more suitable to differentiate toward the neuronal lineage. In addition, the preconditioning of MSCs may improve their beneficial effects. Since it is known that hypoxia may influence stem cell properties, we were interested in evaluating the effects of hypoxia preconditioning on the neuronal differentiation of GMSCs. With this aim, we evaluated the transcriptional profile of GMSCs exposed to basal and neuroinductive medium both in normoxia and in cells preconditioned for 48 h in hypoxia. We compared their transcriptional profile using Next Generation Sequencing. At first we observed that hypoxia did not alter cell morphology compared with the GMSCs cultured in a normoxic condition. In order to understand hypoxia preconditioning effects on neuronal differentiation, we screened genes with Log2 fold change ≥2 using the database Cortecon, that collects gene expression data set of in vitro corticogenesis. We observed that hypoxia preconditioning induced the expression of more genes associated with different stages of cortical development. The common genes, expressed both in normoxia and hypoxia preconditioning, were involved in developmental and neuronal processes. Interestingly, a larger number of genes associated with development biology and neuronal process was expressed in GMSCs differentiated after hypoxia preconditioning compared with those in normoxia. In addition, hypoxic-preconditioned differentiated GMSCs showed a higher expression of nestin, PAX6, and GAP43. Our data demonstrated that hypoxia preconditioning enhanced the differentiation potential of GMSCs and induced the activation of a higher number of genes associated with neuronal development. In conclusion, hypoxia may be used to improve MSCs’ properties for stem cell therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study

et al. 2019

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“…Moreover, AIMP3 enhances mitochondrial respiration and suppresses autophagy, while hypoxia-inducible factor 1α (HIF1α) inhibits AIMP3 [235]. Human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and BM-MSCs show enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence (as indicated by reduced SA-β-gal staining), and increased differentiation ability in hypoxic conditions compared to normoxia [236]. Accordingly, hypoxic-cultured human UC-MSCs showed enhanced proliferation and increased immunosuppressive effects on mitogen-induced mononuclear cell proliferation [157].…”

Section: Msc Rejuvenating Strategiesmentioning

confidence: 99%

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Neri

Borzı̀

2020

Biomolecules

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Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. Beside the fundamental in vivo role of MSCs, they have also emerged in the last years as extremely promising therapeutic agents for a wide variety of clinical conditions. MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. Aging of MSCs (both in vivo and in vitro) can affect not only their replicative potential, but also their properties, like immunomodulation and secretory profile, thus possibly compromising their therapeutic effect. It is therefore of critical importance to unveil the underlying mechanisms of MSC senescence and to define shared methods to assess MSC aging status. The present review will focus on current scientific knowledge about MSC aging mechanisms, control and effects, including possible anti-aging treatments.

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“…The response of MSCs after a stimulus is conditioned by the signals that these cells receive from their surrounding microenvironment [50], such as inflammatory cytokines [51] or hypoxia factors [52]. After a stimulus, MSCs secrete immunoregulatory factors which eventually suppress or enhance the immune response based on the physiological context [49,53].…”

Section: Mscs and Immune Systemmentioning

confidence: 99%

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

Jimenez-Puerta

Marchal

López‐Ruiz

et al. 2020

JCM

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Due to the great therapeutic interest that involves the translation of mesenchymal stromal cells (MSCs) into clinical practice, they have been widely studied as innovative drugs, in order to treat multiple pathologies. MSC-based cell therapy involves the administration of MSCs either locally or systemically into the receptor body where they can traffic and migrate towards the affected tissue and participate in the process of healing. The therapeutic effects of MSCs compromise of different mechanisms such as the functional integration of differentiated MSCs into diseased host tissue after transplantation, their paracrine support, and their impact on the regulation of both the innate and the acquired immune system. Here, we establish and provide recent advances about the principal mechanisms of action through which MSCs can perform their activity and effect as a therapeutic tool. The purpose of this review is to examine and discuss the MSCs capacity of migration, their paracrine effect, as well as MSC-mediated modifications on immune cell responses.

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Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

Cited by 92 publications

References 33 publications

The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study

The Role of Hypoxia on the Neuronal Differentiation of Gingival Mesenchymal Stem Cells: A Transcriptional Study

Molecular Mechanisms Contributing to Mesenchymal Stromal Cell Aging

Role of Mesenchymal Stromal Cells as Therapeutic Agents: Potential Mechanisms of Action and Implications in Their Clinical Use

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