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| DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming.
February 18, 2010 at 6:32 AM
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| | DHP-Derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming. PLoS One. 2010;5(2):e9026 Authors: Jee MK, Kim JH, Han YM, Jung SJ, Kang KS, Kim DW, Kang SK BACKGROUND AND METHODS: In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC). Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions. CONCLUSIONS/SIGNIFICANCE! : Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy. PMID: 20161735 [PubMed - in process] | | |
| Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes.
February 18, 2010 at 6:32 AM
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| | Prenatal Exposure to the Environmental Obesogen Tributyltin Predisposes Multipotent Stem Cells to Become Adipocytes. Mol Endocrinol. 2010 Feb 16; Authors: Kirchner S, Kieu T, Chow C, Casey S, Blumberg B The environmental obesogen hypothesis proposes that pre- and postnatal exposure to environmental chemicals contributes to adipogenesis and the development of obesity. Tributyltin (TBT) is an agonist of both retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARgamma). Activation of these receptors can elevate adipose mass in adult mice exposed to the chemical in utero. Here we show that TBT sensitizes human and mouse multipotent stromal stem cells derived from white adipose tissue [adipose-derived stromal stem cells (ADSCs)] to undergo adipogenesis. In vitro exposure to TBT, or the PPARgamma activator rosiglitazone increases adipogenesis, cellular lipid content, and expression of adipogenic genes. The adipogenic effects of TBT and rosiglitazone were blocked by the addition of PPARgamma antagonists, suggesting that activation of PPARgamma mediates the effect of both compounds on adipogenesis. ADSCs from mice exposed to TBT in utero sho! wed increased adipogenic capacity and reduced osteogenic capacity with enhanced lipid accumulation in response to adipogenic induction. ADSCs retrieved from animals exposed to TBT in utero showed increased expression of PPARgamma target genes such as the early adipogenic differentiation gene marker fatty acid-binding protein 4 and hypomethylation of the promoter/enhancer region of the fatty acid-binding protein 4 locus. Hence, TBT alters the stem cell compartment by sensitizing multipotent stromal stem cells to differentiate into adipocytes, an effect that could likely increase adipose mass over time. PMID: 20160124 [PubMed - as supplied by publisher] | | |
| Effects of milk replacer formulation on measures of mammary growth and composition in Holstein heifers.
February 18, 2010 at 6:32 AM
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| | Effects of milk replacer formulation on measures of mammary growth and composition in Holstein heifers. J Dairy Sci. 2009 Dec;92(12):5937-50 Authors: Daniels KM, Capuco AV, McGilliard ML, James RE, Akers RM Overfeeding prepubertal heifers may impair mammary parenchymal growth and reduce milk production, but evidence suggests that increased intake of a high-protein milk replacer before weaning may be beneficial. This study was designed to evaluate effects of milk replacer (MR) composition on mass and composition of mammary parenchyma and fat pad, growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis gene expression, and putative mammary epithelial stem cells. Specifically, we hypothesized that positive effects of faster rates of gain during the preweaning period alter the development, persistence, or activity of populations of putative mammary epithelial stem cells, possibly through involvement of GH/IGF-I axis molecules. Twenty-four newborn heifers were fed 1 of 4 MR diets (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], high protein, low fat (28% CP, 20% fat MR fed at 951 g of DM/d), high protein, high fat (27% CP! , 28% fat MR fed at 951 g of DM/d), and high protein, high fat+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Water and starter (20% CP, 1.43% fat) were offered ad libitum. Animals were killed on d 65 and mammary tissue was subjected to biochemical, molecular, and histological examination. No differences in mammary parenchymal mass or composition, with or without adjusting for empty body weight, were detected. Mass was increased and composition of the mammary fat pad was altered by nutrient intake. No diet differences in putative mammary epithelial stem cell abundance or abundance of transcripts for genes of the GH/IGF-I axis were detected. In this study, growth of the mammary epithelium, size of the mammary epithelial stem cell population, and components of the GH/IGF-I axis did not depend on diet. However, an underlying positive correlation between telomerase, a marker of mammary stem cells, and growth of the mammary parenchyma was detected. Implications of diet-induced ef! fects on mammary fat pad and possible effects on subsequent de! velopmen t and function remain to be determined. PMID: 19923598 [PubMed - indexed for MEDLINE] | | |
| The role of chemokines in proangiogenic action induced by human adipose tissue-derived mesenchymal stem cells in the murine model of hindlimb ischemia.
February 18, 2010 at 6:32 AM
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| | The role of chemokines in proangiogenic action induced by human adipose tissue-derived mesenchymal stem cells in the murine model of hindlimb ischemia. Cell Physiol Biochem. 2009;24(5-6):511-8 Authors: Cho HH, Kim YJ, Kim JT, Song JS, Shin KK, Bae YC, Jung JS The proangiogenic action of human adipose tissue-derived mesenchymal stem cells (hASCs) transplantation has been shown to be mediated by secretory factors. In this study, we determined if human granulocyte chemotactic protein-2(GCP2) or monocyte chemoattractant protein-1(MCP1) is involved in the proangiogenic action of hASCs transplantation in the hindlimb ischemia model. hASCs secrete GCP2 and MCP1, which leads to increased tubule formation. The downregulation of GCP2 or MCP1 decreased MCP1 and GCP2 secretion, respectively, whereas the external addition of GCP2 or MCP1 increased MCP1 and GCP2, respectively. Additionally, the treatment of GCP2 and MCP1 increased VEGF secretion, while the downregulation of GCP2 and MCP1 showed the opposite effect on VEGF secretion. Downregulation of GCP2 and MCP1 expression also inhibited hASCs-induced proangiogenic action, while the overexpression of GCP2 increased it. Finally, the downregulation of MCP1 or VEGF inhibited the GCP2! overexpression-induced increase in blood flow recovery. Taken together, these data indicate that the proangiogenic action of hASCs transplantation is mediated by the interaction between GCP2, MCP1 and VEGF, which are secreted from the transplanted cells. PMID: 19910691 [PubMed - indexed for MEDLINE] | | |
| Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1.
February 18, 2010 at 6:32 AM
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| | Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev. 2009 Dec;18(10):1399-406 Authors: Lin G, Wang G, Liu G, Yang LJ, Chang LJ, Lue TF, Lin CS Due to the limited supply of donor pancreas, it is imperative that we identify alternative cell sources that can be used to treat diabetes mellitus (DM). Multipotent adipose tissue-derived stem cells (ADSC) can be abundantly and safely isolated for autologous transplantation and therefore are an ideal candidate. Here, we report the derivation of insulin-producing cells from human or rat ADSC by transduction with the pancreatic duodenal homeobox 1 (Pdx1) gene. RT-PCR analyses showed that native ADSC expressed insulin, glucagon, and NeuroD genes that were up-regulated following Pdx1 transduction. ELISA analyses showed that the transduced cells secreted increasing amount of insulin in response to increasing concentration of glucose. Transplantation of these cells under the renal capsule of streptozotocin-induced diabetic rats resulted in lowered blood glucose, higher glucose tolerance, smoother fur, and less cataract. Histological examination showed that the transpla! nted cells formed tissue-like structures and expressed insulin. Thus, ADSC-expressing Pdx1 appear to be suitable for treatment of DM. PMID: 19245309 [PubMed - indexed for MEDLINE] | | | | 
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