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Mesenchymal stem cells (MSC) of bone marrow are the progenitor of osteoblasts and adipocytes. MSC tend to differentiate into adipocytes, instead of osteoblasts, with aging. This favors the loss of bone mass and development of osteoporosis. Hypoxia induces hypoxia inducible factor 1α gene encoding transcription factor, which regulates the expression of genes related to energy metabolism and angiogenesis. That allows a better adaptation to low O
conditions. Sustained hypoxia has negative effects on bone metabolism, favoring bone resorption. Yet, surprisingly, cyclic hypoxia (CH), short times of hypoxia followed by long times in normoxia, can modulate MSC differentiation and improve bone health in aging.
To evaluate the CH effect on MSC differentiation, and whether it improves bone mineral density in elderly.
MSC cultures were induced to differentiate into osteoblasts or adipocytes, in CH (3% O
for 1, 2 or 4 h, 4 d a week). Extracellular-matrix mineralization and lipid-droplet formation were studied inrly, due to its possible inhibitory effect on bone resorption, by increasing the osteoprotegerin / receptor activator for nuclear factor kappa B ligand ratio.
Impaired wound healing can be associated with different pathological states. Ertugliflozin Burn wounds are the most common and detrimental injuries and remain a major health issue worldwide. Mesenchymal stem cells (MSCs) possess the ability to regenerate tissues by secreting factors involved in promoting cell migration, proliferation and differentiation, while suppressing immune reactions. Preconditioning of MSCs with small molecules having cytoprotective properties can enhance the potential of these cells for their use in cell-based therapeutics.
To enhance the therapeutic potential of MSCs by preconditioning them with isorhamnetin for second degree burn wounds in rats.
Human umbilical cord MSCs (hU-MSCs) were isolated and characterized by surface markers, CD105, vimentin and CD90. For preconditioning, hU-MSCs were treated with isorhamnetin after selection of the optimized concentration (5 µmol/L) by cytotoxicity analysis. The migration potential of these MSCs was analyzed by the
scratch assay. The healing potentth factor, Bcl-2 and matrix metallopeptidase 9 showed significant upregulation compared to the burn wound, showing increased angiogenesis and reduced inflammation and apoptosis.
Preconditioning of hU-MSCs with isorhamnetin decreases wound progression by reducing inflammation, and improving tissue architecture and wound healing. The study outcome is expected to lead to an improved cell-based therapeutic approach for burn wounds.
Preconditioning of hU-MSCs with isorhamnetin decreases wound progression by reducing inflammation, and improving tissue architecture and wound healing. The study outcome is expected to lead to an improved cell-based therapeutic approach for burn wounds.
Human adipose-derived stromal/stem cells (hASCs) are one of the most useful types of mesenchymal stromal/stem cells, which are adult multipotent cells with great therapeutic potential for the treatment of several diseases. However, for successful clinical application, it is critical that high-quality cells can be obtained. Diverse factors seem to be able to influence cell quality and performance, especially factors related to donors' intrinsic characteristics, such as age. Nevertheless, there is no consensus regarding this characteristic, and there is conflicting information in the literature.
To investigate the growth kinetics and differentiation potential of adipose-derived stem cells isolated from the lipoaspirates of elderly and young donors.
hASCs were harvested from liposuctioned adipose tissue obtained from female donors (aged 20-70 years). Cells were distributed into two groups according to age range old hASCs (oASCs, ≥ 55 years,
= 9) and young hASCs (yASCs, ≤ 35 years,
= 9). For each grou, after adipogenic and osteogenic induction, yASCs and oASCs were able to differentiate to greater levels than the noninduced control cells. However, no differences were found in the differentiation efficiency of yASCs and oASCs in adipogenesis or osteogenesis. Additionally, the mRNA expression of PPARγ2, CEBPA and Runx2 were similar in yASCs and oASCs.
Our findings suggest that age does not seem to significantly affect the cell division or adipogenic or osteogenic differentiation ability of adipose-derived stem cells isolated from lipoaspirates.
Our findings suggest that age does not seem to significantly affect the cell division or adipogenic or osteogenic differentiation ability of adipose-derived stem cells isolated from lipoaspirates.
Autoimmune hepatitis is a serious autoimmune liver disease that threatens human health worldwide, which emphasizes the urgent need to identify novel treatments. Stem cells from human exfoliated deciduous teeth (SHED), which are easy to obtain in a non-invasive manner, show pronounced proliferative and immunomodulatory capacities.
To investigate the protective effects of SHED on concanavalin A (ConA)-induced hepatitis in mice, and to elucidate the associated regulatory mechanisms.
We used a ConA-induced acute hepatitis mouse model and an
co-culture system to study the protective effects of SHED on ConA-induced autoimmune hepatitis, as well as the associated underlying mechanisms.
SHED infusion could prevent aberrant histopathological liver architecture caused by ConA-induced infiltration of CD3
, CD4
, tumor necrosis-alpha
, and interferon-gamma
inflammatory cells. Alanine aminotransferase and aspartate aminotransferase were significantly elevated in hepatitis mice. SHED infusion could therefore block ConA-induced alanine aminotransferase and aspartate aminotransferase elevations. Mechanistically, ConA upregulated tumor necrosis-alpha and interferon-gamma expression, which was activated by the nuclear factor-kappa B pathway to induce hepatocyte apoptosis, resulting in acute liver injury. SHED administration protected hepatocytes from ConA-induced apoptosis.
SHED alleviates ConA-induced acute liver injury
inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.
SHED alleviates ConA-induced acute liver injury via inhibition of hepatocyte apoptosis mediated by the nuclear factor-kappa B pathway. Our findings could provide a potential treatment strategy for hepatitis.
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