Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells

Safwani, Wan Kamarul Zaman Wan; Choi, Jane Ru; Yong, Kar Wey; Ting, Iris; Adenan, Noor Azmi Mat; Murphy, Belinda

doi:10.1016/j.cryobiol.2017.01.006

Cited by 50 publications

(38 citation statements)

References 30 publications

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“…Hypoxia, besides promoting chondrogenic differentiation of hASCs [16], also downregulates osteogenesis [51] and inhibits endochondral ossification with low expression in Runx2 and COL10A1 [52]. Notably, Xu et al [53] found that hypoxic preconditioning enhanced the chondrogenic differentiation and decreased osteogenic differentiation of murine ASCs.…”

Section: Discussionmentioning

confidence: 99%

“…In line with this, the microenvironment of hASCs in vivo is also characterized by low oxygen pressure. It has been suggested that hypoxia reduces their potential for osteogenic differentiation [16] while promoting chondral extracellular matrix (ECM) formation [17]. In fact, chondrocyte markers such as SOX9, collagen type II (COL2A1) and aggrecan are positively regulated by hypoxic conditions [18].…”

Section: Introductionmentioning

confidence: 99%

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Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

Zubillaga

Alonso‐Varona

Fernandes

et al. 2020

IJMS

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Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

Zubillaga

Alonso‐Varona

Fernandes

et al. 2020

IJMS

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“…However, they demonstrated chondrogenic differentiation by alcian blue staining without any quantitative data on the mRNA expression of the chondrogenic markers. Other studies have demonstrated that low oxygen tension increased the ADMSC stemness marker expression and proliferation rate without altering their morphology and surface markers [ 30 , 31 ]. Low oxygen tension further enhances the chondrogenic differentiation ability but reduces both adipogenic and osteogenic differentiation potential [ 32 – 34 ].…”

Section: Discussionmentioning

confidence: 99%

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

Teti

Focaroli

Salvatore

et al. 2018

Stem Cells International

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Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1α), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated. Cells were treated with concentrations of CoCl2 ranging from 50 to 400 μM. Cell viability, HIF-1α protein synthesis, and the expression of the chondrogenic markers were analyzed. The results showed that the CoCl2 supplementation had no effect on cell viability, while the upregulation of chondrogenic markers such as SOX9, COL2A1, VCAN, and ACAN was dependent on the cellular source. This study shows that hypoxia, induced by CoCl2 treatment, can differently influence the behavior of MSCs, isolated from different sources, in their chondrogenic potential. These findings should be taken into consideration in the treatment of cartilage repair and regeneration based on stem cell therapies.

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“…Additionally, the frequency of MSC divisions increases at low oxygen concentrations with the intact genotype maintained [ 105 ]. An increase in the chondrogenic potential of MSCs caused by hypoxia has been reported [ 104 , 106 ], although—as with chondrocytes—the direction of MSCs differentiation depends on the oxygen concentration but also on other factors, such as the substrate used [ 107 , 108 ].…”

Section: Possible Anti-aging Strategiesmentioning

confidence: 99%

Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

Krajewska–Włodarczyk

Owczarczyk‐Saczonek

Placek

et al. 2018

IJMS

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Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage.

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Hypoxia enhances the viability, growth and chondrogenic potential of cryopreserved human adipose-derived stem cells

Cited by 50 publications

References 30 publications

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

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

Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy

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