1.
Simulated microgravity significantly altered metabolism in epidermal stem cells.
Li, BB, Chen, ZY, Jiang, N, Guo, S, Yang, JQ, Chai, SB, Yan, HF, Sun, PM, Hu, G, Zhang, T, et al
In vitro cellular & developmental biology. Animal. 2020;(3):200-212
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Abstract
Simulated microgravity can significantly affect various cell types and multiple systems of the human body, such as cardiovascular system, skeletal muscle system, and immune system, and is known to cause anemia and loss of electrolyte and fluids. Epidermal stem cells (EpSCs) were cultured in a rotary cell culture system (RCCS) bioreactor to simulate microgravity. The metabolites of EpSCs were identified by liquid chromatography-mass spectrometry (LC-MS). Compared with normal gravity (NG) group, a total of 57 different metabolites of EpSCs were identified (P < 0.05, VIP > 1), including lipids and lipid-like molecules (51 molecules), amino acids (5 molecules), nucleosides, nucleotides, and analogues (1 molecule). According to the partial least squares discriminant analysis (PLS-DA) score plot, a VIP > 1 and P < 0.05 were obtained for the 57 different metabolites, of which 23 molecules were significantly downregulated and 34 were significantly upregulated in simulated microgravity (SMG) group. These results showed that SMG has a significant impact on different pathways, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that multiple pathways were involved, mainly the amino acid metabolism pathway, lipid metabolism pathway, membrane transport pathway, and cell growth and death pathways. Thus, the metabolic profile of EpSCs was changed under SMG. Exploring the metabolic profile of EpSCs would be helpful to further understand the growth characteristics of EpSCs under SMG, which will provide a new approach to explore the metabolomics mechanism of stress injury and repair trauma under SMG.
2.
Intestinal Regeneration: Regulation by the Microenvironment.
Hageman, JH, Heinz, MC, Kretzschmar, K, van der Vaart, J, Clevers, H, Snippert, HJG
Developmental cell. 2020;(4):435-446
Abstract
Damage to the intestinal stem cell niche can result from mechanical stress, infections, chronic inflammation or cytotoxic therapies. Progenitor cells can compensate for insults to the stem cell population through dedifferentiation. The microenvironment modulates this regenerative response by influencing the activity of signaling pathways, including Wnt, Notch, and YAP/TAZ. For instance, mesenchymal cells and immune cells become more abundant after damage and secrete signaling molecules that promote the regenerative process. Furthermore, regeneration is influenced by the nutritional state, microbiome, and extracellular matrix. Here, we review how all these components cooperate to restore epithelial homeostasis in the intestine after injury.
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Endothelial Regenerative Capacity and Aging: Influence of Diet, Exercise and Obesity.
Ross, MD
Current cardiology reviews. 2018;(4):233-244
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Abstract
BACKGROUND The endothelium plays an important role in cardiovascular regulation, from blood flow to platelet aggregation, immune cell infiltration and demargination. A dysfunctional endothelium leads to the onset and progression of Cardiovascular Disease (CVD). The aging endothelium displays significant alterations in function, such as reduced vasomotor functions and reduced angiogenic capabilities. This could be partly due to elevated levels of oxidative stress and reduced endothelial cell turnover. Circulating angiogenic cells, such as Endothelial Progenitor Cells (EPCs) play a significant role in maintaining endothelial health and function, by supporting endothelial cell proliferation, or via incorporation into the vasculature and differentiation into mature endothelial cells. However, these cells are reduced in number and function with age, which may contribute to the elevated CVD risk in this population. However, lifestyle factors, such as exercise, physical activity obesity, and dietary intake of omega-3 polyunsaturated fatty acids, nitrates, and antioxidants, significantly affect the number and function of these circulating angiogenic cells. CONCLUSION This review will discuss the effects of advancing age on endothelial health and vascular regenerative capacity, as well as the influence of diet, exercise, and obesity on these cells, the mechanistic links and the subsequent impact on cardiovascular health.
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Advanced Gene Manipulation Methods for Stem Cell Theranostics.
Rathnam, C, Chueng, SD, Yang, L, Lee, KB
Theranostics. 2017;(11):2775-2793
Abstract
In the field of tissue engineering, autologous cell sources are ideal to prevent adverse immune responses; however, stable and reliable cell sources are limited. To acquire more reliable cell sources, the harvesting and differentiation of stem cells from patients is becoming more and more common. To this end, the need to control the fate of these stem cells before transplantation for therapeutic purposes is urgent. Since transcription factors orchestrate all of the gene activities inside of a cell, researchers have developed engineered and synthetic transcription factors to precisely control the fate of stem cells allowing for safer and more effective cell sources. Engineered transcription factors, mutant fusion proteins of naturally occurring proteins, comprise the three main domains of natural transcription factors including DNA binding domains, transcriptional activation domains, and a linker domain. Several key advancements of engineered zinc finger proteins, transcriptional activator-like effectors, and deficient cas9 proteins have revolutionized the field of engineered transcription factors allowing for precise control of gene regulation. Synthetic transcription factors are chemically made transcription factor mimics that use small molecule based moieties to replicate the main functions of natural transcription factors. These include hairpin polyamides, triple helix forming oligonucleotides, and nanoparticle-based methods. Synthetic transcription factors allow for non-viral delivery and greater spatiotemporal control of gene expression. The developments in engineered and synthetic transcription factors have lowered the risk of tumorigenicity and improved differentiation capability of stem cells, as well as facilitated many key discoveries in the fields of cancer and stem cell biology, thus providing a stepping stone to advance regenerative medicine in the clinic for cell replacement therapies.