Autophagy, Mesenchymal Stem Cell Differentiation, and Secretion

Menshikov, Mikhail; Zubkova, Ekaterina; Stafeev, Iurii; Parfyonova, Yelena

doi:10.3390/biomedicines9091178

Cited by 22 publications

(17 citation statements)

References 115 publications

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“…Moreover, it has been shown that autophagy protects the cells from senescence [ 39 ], contributes to their rejuvenation [ 40 ], and shows a potential key contribution to hASCs’ therapeutic action [ 20 , 47 ] by providing a vital activity to cells. In fact, it has also been postulated that there is a relationship between autophagy and some signals that regulate the transduction mechanism directly involved in their differentiation [ 48 ], such as wingless/integrated (Wnt)/β-catenin, neurogenic locus notch homolog protein (Notch), and NF-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signaling. All these autophagy functions on cells might represent an interesting way to improve the differentiation of hASCs for purposes of cartilage regeneration.…”

Section: Resultsmentioning

confidence: 99%

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Gabusi

Lenzi

Manferdini

et al. 2022

Gels

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Autophagy is a cellular process that contributes to the maintenance of cell homeostasis through the activation of a specific path, by providing the necessary factors in stressful and physiological situations. Autophagy plays a specific role in chondrocyte differentiation; therefore, we aimed to analyze this process in adipose-derived mesenchymal stromal cells (ASCs) laden in three-dimensional (3D) hydrogel. We analyzed chondrogenic and autophagic markers using molecular biology, immunohistochemistry, and electron microscopy. We demonstrated that ASCs embedded in 3D hydrogel showed an increase expression of typical autophagic markers Beclin 1, LC3, and p62, associated with clear evidence of autophagic vacuoles in the cytoplasm. During ASCs chondrogenic differentiation, we showed that autophagic markers declined their expression and autophagic vesicles were rare, while typical chondrogenic markers collagen type 2, and aggrecan were significantly increased. In line with developmental animal models of cartilage, our data showed that in a 3D hydrogel, ASCs increased their autophagic features. This path is the fundamental prerequisite for the initial phase of differentiation that contributes to fueling the cells with energy and factors necessary for chondrogenic differentiation.

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Section: Resultsmentioning

confidence: 99%

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Gabusi

Lenzi

Manferdini

et al. 2022

Gels

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“…This alkaloid has been used as therapeutic target against multiple diseases including amoebiasis (FDA approved), leukemia, Zikavirus, Ebolavirus, cytomegalovirus and SARS-CoV-2 infection (46-50), and was identified as an inhibitor regulating cell autophagy (46). Autophagy is an essential process for adipogenic differentiation (51). Inhibition of autophagy is of significant importance to alter differentiation state and metabolic function of adipocytes.…”

Section: Identification Of Two Novel Compounds That Inhibit Bmsc-deri...mentioning

confidence: 99%

Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map

Zhang

Lyons²,

Koedam³

et al. 2022

Front. Endocrinol.

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Several physiological and pathological conditions such as aging, obesity, diabetes, anorexia nervosa are associated with increased adipogenesis in the bone marrow. A lack of effective drugs hinder the improved treatment for aberrant accumulation of bone marrow adipocytes. Given the higher costs, longer duration and sometimes lack of efficacy in drug discovery, computational and experimental strategies have been used to identify previously approved drugs for the treatment of diseases, also known as drug repurposing. Here, we describe the method of small molecule-prioritization by employing adipocyte-specific genes using the connectivity map (CMap). We then generated transcriptomic profiles using human mesenchymal stromal cells under adipogenic differentiation with the treatment of prioritized compounds, and identified emetine and kinetin-riboside to have a potent inhibitory effect on adipogenesis. Overall, we demonstrated a proof-of-concept method to identify repurposable drugs capable of inhibiting adipogenesis, using the Connectivity Map.

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“…MSCs are a heterogeneous cell population originating from the mesoderm in the early stage of embryonic development, 7 and include stem cells and differentiated progeny from the early stage of embryonic development and subsequent developmental stages. 8 As one of the most easily obtained primary cells, MSCs can be isolated from a variety of tissues, such as the umbilical cord, adipose tissue, dermis, tendons, bone marrow, muscles, and dental pulp.…”

Section: Introductionmentioning

confidence: 99%

Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics

Wang¹,

Lei²,

Zhang³

et al. 2022

IJN

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Inflammation is a beneficial and physiological process, but there are a number of inflammatory diseases which have detrimental effects on the body. In addition, the drugs used to treat inflammation have toxic side effects when used over a long period of time. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can be isolated from a variety of tissues and can be differentiate into diverse cell types under appropriate conditions. They also exhibit noteworthy anti-inflammatory properties, providing new options for the treatment of inflammatory diseases. The therapeutic potential of MSCs is currently being investigated for various inflammatory diseases, such as kidney injury, lung injury, osteoarthritis (OA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSCs can perform multiple functions, including immunomodulation, homing, and differentiation, to enable damaged tissues to form a balanced inflammatory and regenerative microenvironment under severe inflammatory conditions. In addition, accumulated evidence indicates that exosomes from extracellular vesicles of MSCs (MSC-Exos) play an extraordinary role, mainly by transferring their components to recipient cells. In this review, we summarize the mechanism and clinical trials of MSCs and MSC-Exos in various inflammatory diseases in detail, with a view to contributing to the treatment of MSCs and MSC-Exos in inflammatory diseases.

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Autophagy, Mesenchymal Stem Cell Differentiation, and Secretion

Cited by 22 publications

References 115 publications

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Autophagy Is a Crucial Path in Chondrogenesis of Adipose-Derived Mesenchymal Stromal Cells Laden in Hydrogel

Identification of small molecules as novel anti-adipogenic compounds based on Connectivity Map

Targeted Therapy for Inflammatory Diseases with Mesenchymal Stem Cells and Their Derived Exosomes: From Basic to Clinics

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