Age-Related Changes in the Inflammatory Status of Human Mesenchymal Stem Cells: Implications for Cell Therapy

Zhang, Ying; Ravikumar, Maanasa; Ling, Ling; Nurcombe, Victor; Cool, Simon M.

doi:10.1016/j.stemcr.2021.01.021

Cited by 63 publications

(57 citation statements)

References 96 publications

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“…Senescent cells have been shown to possess a characteristic secretome, called senescenceassociated secretory phenotype (SASP) [174], characterized by the production of cytokines, chemokines, growth factors, proteases, and reactive oxygen species; these together modify the local and systemic environment. The SASP acts in an autocrine way, reinforcing the arrest of cell growth, while in a paracrine way it induces senescence in neighboring cells, remodels the extracellular matrix, affects the stem cell niches, and stimulates the recruitment and activation of immune cells favoring an inflammatory state [174][175][176]. It has been reported that TA-MSC treatment of healthy donors with 20 ng/mL of TNF-α for 24 h induces SASP with increased expression of IL-6, IL-8, and monocyte chemotactic protein-1 (MCP-1) [172].…”

Section: Alterations In Cell Morphology and Proliferationmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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Mesenchymal stem/stromal cells (MSCs) have an immunoregulatory capacity and have been used in different clinical protocols requiring control of the immune response. However, variable results have been obtained, mainly due to the effect of the microenvironment on the induction, increase, and maintenance of MSC immunoregulatory mechanisms. In addition, the importance of cell–cell contact for MSCs to efficiently modulate the immune response has recently been highlighted. Because these interactions would be difficult to achieve in the physiological context, the release of extracellular vesicles (EVs) and their participation as intermediaries of communication between MSCs and immune cells becomes relevant. Therefore, this article focuses on analyzing immunoregulatory mechanisms mediated by cell contact, highlighting the importance of intercellular adhesion molecule-1 (ICAM-1) and the participation of EVs. Moreover, the effects of tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), the main cytokines involved in MSC activation, are examined. These cytokines, when used at the appropriate concentrations and times, would promote increases in the expression of immunoregulatory molecules in the cell and allow the acquisition of EVs enriched with these molecules. The establishment of certain in vitro activation guidelines will facilitate the design of conditioning protocols to obtain functional MSCs or EVs in different pathophysiological conditions.

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Section: Alterations In Cell Morphology and Proliferationmentioning

confidence: 99%

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

López-García

Castro-Manrreza

2021

IJMS

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“…Clinically, osteogenic ability of BMSCs is weakened under some pathophysiological conditions, such as aging, menopause, trauma, and inflammation, all of which can lead to bone defects and osteoporosis [ 2 – 4 , 33 ]. We found that quercetin treatment induced BMSC proliferation and osteogenic differentiation, suggesting that quercetin can be used for the clinical treatment of osteoporosis and bone defects.…”

Section: Discussionmentioning

confidence: 99%

“…Human bone marrow mesenchymal stem cells (BMSCs) can undergo self-renewal and osteogenic differentiation, and play a vital function for bone formation and remodeling [1]. Some pathophysiological conditions, such as aging, osteoporosis, and some bone defects can inhibit the osteogenic ability of BMSCs [2][3][4]. Therefore, drugs Bian et al BMC Complement Med Ther (2021) 21:243 that can regulate BMSC osteogenic differentiation need to be developed for the management and treatment of these orthopedic diseases.…”

Section: Introductionmentioning

confidence: 99%

Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/β-catenin pathway

Bian

Xiao

Yang

et al. 2021

BMC Complement Med Ther

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Background Quercetin and H19 can promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, whether quercetin regulates H19 expression to promote osteogenic differentiation of BMSCs is unclear. Methods BMSC proliferation, matrix mineralization, and alkaline phosphatase (ALP) activity were assessed using the Cell Counting Kit-8, ALP assay kit, and alizarin red staining kit, respectively. Expression of H19, miR-625-5p, BMP-2, osteocalcin, and RUNX2 were measured by qRT-PCR; β-catenin protein level was measured by western blotting. Results Quercetin promoted BMSC proliferation, enhanced ALP activity, and upregulated the expression of BMP-2, osteocalcin, and RUNX2 mRNAs, suggesting that it promoted osteogenic differentiation of BMSCs. Moreover, quercetin increased H19 expression, while the effect of quercetin on BMSCs was reversed by silencing H19 expression. Additionally, miR-625-5p, interacted with H19, was downregulated during quercetin-induced BMSC osteogenic differentiation, which negatively correlated with H19 expression. Silencing miR-625-5p expression promoted BMSC proliferation and osteogenic differentiation, whereas miR-625-5p overexpression weakened the effect of quercetin on BMSCs. Finally, quercetin treatment or downregulation of miR-625-5p expression increased β-catenin protein level in BMSCs. Upregulation or downregulation of miR-625-5p or H19 expression, respectively, inhibited β-catenin protein level in quercetin treated-BMSCs. Conclusion H19 promotes, while miR-625-5p inhibits BMSC osteogenic differentiation. Quercetin activates the Wnt/β-catenin pathway and promotes BMSC osteogenic differentiation via the H19/miR-625-5p axis.

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“…This initial work in sustained microgravity conditions indicates that such an environment can lead to the identification of novel targets for enhancing the therapeutic benefit of cardiovascular stem cells or progenitor cells (Camberos, V., et al 2021, Camberos, V., et al 2019, Baio, J., et al 2018.  Expansion of mesenchymal stem cells (MSCs) with improved clinical properties: While stem cells hold great potential for use as therapeutic agents, safe and efficient expansion of stem cells is still a major challenge in the field (Zhang, Y., et al 2021). MSCs are emerging as the most common stem cell type utilized within the field of regenerative medicine (Research and Markets, 2021).…”

Section: Cells With Increased Potency and Expansion Capabilitiesmentioning

confidence: 99%

Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

Giulianotti¹,

Sharma²,

Clemens³

et al. 2021

Preprint

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In humankind’s endeavor to explore beyond our planet and travel further into space, we are now at the threshold of an era in which it is possible to move to and from low Earth orbit (LEO) with increasing ease and reduced cost. Through the International Space Station (ISS) U.S. National Laboratory, investigators from industry, academia, and government can easily access the unique LEO environment on the ISS to conduct research and development (R&D) activities in ways not possible on Earth. A key advantage of the LEO environment for life sciences research is the ability to conduct experiments in sustained microgravity conditions. The ability to conduct long-term research in microgravity enables opportunities for novel, fundamental studies in tissue engineering and regenerative medicine, including research on stem cell proliferation and differentiation, biofabrication, and disease modeling using microphysiological systems (MPS) that build on prior research using simulated microgravity conditions (Grimm, D., et al. 2018). Over the last decade, space-based research has demonstrated that microgravity informs our knowledge of fundamental biology and accelerates advancements in health care and medical technologies (International Space Station 2019). The benefits provided by conducting biomedical research in LEO may lead to breakthroughs not achievable on Earth. We are now at a transition point, in which nations are changing their approach to space-based R&D. The focus is shifting from government-funded fundamental science toward the expansion of privately funded R&D with terrestrial application and economic value that will drive a robust marketplace for innovation and manufacturing in LEO. Making this long-term transition requires public-private participation and near-term funding to support critical R&D to leverage the benefits of the LEO environment and de-risk space-based research. Studies conducted on the ISS over the past several years have indicated that one area with potential significant economic value and benefit to life on Earth is space-based biomanufacturing, or the use of biological and nonbiological materials to produce commercially relevant biomolecules and biomaterials for use in preclinical, clinical, and therapeutic applications. We must take advantage of the remaining lifetime of the ISS as a valuable LEO platform to demonstrate this economic value and Earth benefit. By facilitating access to the space station, the ISS National Lab is uniquely positioned to enable the R&D necessary to bridge the gap between the initial discovery phase of space-based biomedical research and the development of a sustainable, investment-worthy biomanufacturing market in LEO supported by future commercial platforms. Through a joint effort, the Center for the Advancement of Science in Space (CASIS), which manages the ISS National Lab, and the University of Pittsburgh’s McGowan Institute for Regenerative Medicine brought together thought leaders from around the U.S. for a Biomanufacturing in Space Symposium that consisted of a series of working sessions to review data from past space-based tissue engineering and regenerative medicine research, discuss relevant current space-based R&D in this area, and consider potential future markets to address the questions: What are the most promising opportunities to leverage the ISS to advance space-based biomanufacturing moving forward? What are the current gaps or barriers that, if overcome, could clear pathways toward private investment in LEO as a valued site for research, development, and production activity? And, most importantly: For which opportunities do the most compelling value propositions exist? The goal of the Biomanufacturing in Space Symposium was to help identify the specific areas in which government and industry investment would be most likely to stimulate advancements that overcome barriers. This would lead to a more investment-ready landscape for private interests to enter the market and fuel exponential growth. The symposium was meant to serve as the first step in developing a roadmap to a sustainable market for biomanufacturing in space. The symposium identified and prioritized multiple key R&D opportunities to advance space-based biomanufacturing. These opportunities fall in the areas of disease modeling, stem cells and stem-cell-derived products, and biofabrication. Additionally, symposium participants highlighted the critical need for additional data to help validate and de-risk these opportunities and concluded that approaches such as automation, artificial intelligence (AI), and machine learning will be needed to produce and capture the required data. Symposium participants also came to a consensus that public-private partnerships and funding will be needed to advance the opportunities toward a biomanufacturing marketplace in LEO. This paper will summarize the current state of the science and technology on the ISS and in the fields of tissue engineering and regenerative medicine; provide an overview of biomanufacturing R&D in space to date; review the goals of the Biomanufacturing in Space Symposium; highlight the key commercial opportunities and gaps identified during the symposium; provide information on potential market sizes; and briefly discuss the next steps in developing a roadmap to biomanufacturing in space.

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Age-Related Changes in the Inflammatory Status of Human Mesenchymal Stem Cells: Implications for Cell Therapy

Cited by 63 publications

References 96 publications

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

TNF-α and IFN-γ Participate in Improving the Immunoregulatory Capacity of Mesenchymal Stem/Stromal Cells: Importance of Cell–Cell Contact and Extracellular Vesicles

Quercetin promotes bone marrow mesenchymal stem cell proliferation and osteogenic differentiation through the H19/miR-625-5p axis to activate the Wnt/β-catenin pathway

Opportunities for Biomanufacturing in Low Earth Orbit: Current Status and Future Directions

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