Browsing by Subject "Mesenchymal stromal cells"

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    Differential Iron Requirements for Osteoblast and Adipocyte Differentiation
    (Wiley, 2021-07-26) Edwards, Daniel F., III.; Miller, Christopher J.; Quintana-Martinez, Arelis; Wright, Christian S.; Prideaux, Matthew; Atkins, Gerald J.; Thompson, William R.; Clinkenbeard, Erica L.; Medical and Molecular Genetics, School of Medicine
    Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome-proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis.
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    Impact of allogeneic feline uterine-derived mesenchymal stromal cell intravenous treatment on renal function of nephrectomized cats with chronic kidney disease
    (Elsevier, 2021) Zacharias, Shelly; Welty, Matthew B.; Sand, Theodore T.; Black, Linda L.; Medical and Molecular Genetics, School of Medicine
    Chronic kidney disease (CKD) is a common condition and leading cause of mortality in cats. Mesenchymal stromal cells (MSCs) may have a therapeutic effect on CKD. The aim of this pilot study was to determine efficacy of systemically-administered allogeneic uterine tissue-derived MSCs (UMSCs) in cats with CKD. Eighteen renal-compromised, unilaterally nephrectomized cats received two doses of 3 × 107 allogeneic UMSCs given intravenously (IV) with a 2-week dose interval. The primary endpoint was renal function, with treatment success defined by a 20% increase in glomerular filtration rate (GFR; iohexol clearance) and/or a 20% decrease in plasma creatinine in 50% of the cats. Secondary endpoints included diet and water consumption, body weight, urine characteristics, and adverse events. Treatment was well tolerated and associated with a statistically meaningful increase in GFR on Days 13, 28, 57, 99, 121 and 182, compared with baseline (P < 0.0001 for Days 13 to 99 inclusive; P = 0.0029 and P = 0.0225 for Days 121 and 182, respectively). Greater than 50% of the cats demonstrated a 20% increase in GFR on all days except Day 150, at which point GFR measurements were consistently above baseline. Statistically meaningful increases in diet and water consumption were observed. Substantial improvements in GFR were observed throughout the six-month evaluation period (excluding Day 150) in more than 50% of cats, thereby meeting the primary endpoint. Therefore, this IV-administered, allogeneic cellular therapy may support both renal function and clinical status of cats with CKD.