The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Teti, Gabriella; Focaroli, Stefano; Salvatore, Viviana; Mazzotti, Eleonora; Ingrà, Laura; Mazzotti, Antonio; Falconi, Mirella

doi:10.1155/2018/3237253

Cited by 45 publications

(33 citation statements)

References 39 publications

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“…Severe and prolonged hypoxia may induce apoptosis, whereas acute and mild hypoxia induce adaptation and survival (Greijer and van der Wall 2004). Although previous studies have reported that dental-derived cells such as DPSCs and hPDLCs have high cell viability when cultured in 100 μM CoCl 2 (Osathanon et al 2015;Teti et al 2018), contradictory findings have also been reported, namely, that 100 μM CoCl 2 induced cell death (Laksana et al 2017). These conflicting results may be due to variations in cell types and experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Chen

Zhao

Yang

et al. 2019

Cell Stress and Chaperones

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Stem cells from human exfoliated deciduous teeth (SHEDs) are a promising source for tissue engineering and stem cell transplantation. However, long-term in vitro culture and expansion lead to the loss of stemness of SHEDs, compromising their therapeutic benefits. Hypoxia plays an essential role in controlling the stem cell behavior of mesenchymal stem cells (MSCs). Thus, this study aimed to investigate the effects of cobalt chloride (CoCl 2), a hypoxia-mimetic agent, on the stem cell marker expression and osteogenic differentiation of SHEDs. SHEDs were cultured with or without 50 or 100 μM CoCl 2. Their proliferation, apoptosis, stem cell marker expression, migration ability, and osteogenic differentiation were examined. Culture with 50 and 100 μM CoCl 2 increased the hypoxiainducible factor-1 alpha (HIF-1α) protein levels in a dose-dependent manner in SHEDs without inducing significant cytotoxicity. This effect was accompanied by an increase in the proportion of STRO-1 + cells. CoCl 2 significantly increased the expression of stem cell markers (OCT4, NANOG, SOX2, and c-Myc) in a dose-dependent manner. The migration ability was also promoted by CoCl 2 treatment. Furthermore, SHEDs cultured in osteogenic medium with CoCl 2 showed a dose-dependent reduction in alkaline phosphatase (ALP) activity and calcium deposition. The expression of osteogenic-related genes was also suppressed by CoCl 2 , especially in the 100-μM CoCl 2 group. In conclusion, CoCl 2 increased the expression of stem cell markers and inhibited the osteogenic differentiation of SHEDs. These findings may provide evidence supporting the use of in vitro hypoxic environments mimicked by CoCl 2 in assisting the clinical application of SHEDs.

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Section: Discussionmentioning

confidence: 99%

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Chen

Zhao

Yang

et al. 2019

Cell Stress and Chaperones

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“…Other hydroxylase inhibitors have also been used to create a physioxia mimicking response, specifically dimethyloxalylglycine (a competitive inhibitor of PHDs and FIHs) and desferrioxamine (sequesters iron ions). Although this review primarily focusses on experiments that use altered incubator oxygen levels, studies utilising chemically-induced physioxic responses are discussed where appropriate [36,39,40].…”

Section: Physioxia and Cartilagementioning

confidence: 99%

The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response

Pattappa

Johnstone

Zellner

et al. 2019

IJMS

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Articular cartilage covers the surface of synovial joints and enables joint movement. However, it is susceptible to progressive degeneration with age that can be accelerated by either previous joint injury or meniscectomy. This degenerative disease is known as osteoarthritis (OA) and it greatly affects the adult population. Cell-based tissue engineering provides a possible solution for treating OA at its earliest stages, particularly focal cartilage lesions. A candidate cell type for treating these focal defects are Mesenchymal Stem Cells (MSCs). However, present methods for differentiating these cells towards the chondrogenic lineage lead to hypertrophic chondrocytes and bone formation in vivo. Environmental stimuli that can stabilise the articular chondrocyte phenotype without compromising tissue formation have been extensively investigated. One factor that has generated intensive investigation in MSC chondrogenesis is low oxygen tension or physioxia (2–5% oxygen). In vivo articular cartilage resides at oxygen tensions between 1–4%, and in vitro results suggest that these conditions are beneficial for MSC expansion and chondrogenesis, particularly in suppressing the cartilage hypertrophy. This review will summarise the current literature regarding the effects of physioxia on MSC chondrogenesis with an emphasis on the pathways that control tissue formation and cartilage hypertrophy.

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“…Currently, MSCs still represent a good candidate for tissue repair and regeneration [2,3]. MSCs or mesenchymal progenitor cells can be defined as non-hematopoietic, self-renewing cells that can be expanded ex vivo and induced to terminally differentiate, under certain conditions, into cells of mesenchymal lineage, including osteoblasts [4,5], chondrocytes [6,7,8], adipocytes [9], and hematopoietic-supporting stroma [10].…”

Section: Introductionmentioning

confidence: 99%

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

Mazzotti

Teti

Falconi

et al. 2019

Cells

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Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs’ biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs’ characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.

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The Hypoxia-Mimetic Agent Cobalt Chloride Differently Affects Human Mesenchymal Stem Cells in Their Chondrogenic Potential

Cited by 45 publications

References 39 publications

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

Effects of cobalt chloride on the stem cell marker expression and osteogenic differentiation of stem cells from human exfoliated deciduous teeth

The Importance of Physioxia in Mesenchymal Stem Cell Chondrogenesis and the Mechanisms Controlling Its Response

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model

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