The Experts below are selected from a list of 8529 Experts worldwide ranked by ideXlab platform
Jianjun Guan - One of the best experts on this subject based on the ideXlab platform.
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high oxygen preservation hydrogels to augment cell survival under Hypoxic Condition
Acta Biomaterialia, 2020Co-Authors: Hong Niu, Jianjun Guan, Ya Guan, Yu Dang, Zhaobo Fan, Jie ShenAbstract:Abstract Cell therapy is a promising approach for ischemic tissue regeneration. However, high death rate of delivered cells under low oxygen Condition, and poor cell retention in tissues largely limit the therapeutic efficacy. Using cell carriers with high oxygen preservation has potential to improve cell survival. To increase cell retention, cell carriers that can quickly solidify at 37 °C so as to efficiently immobilize the carriers and cells in the tissues are necessary. Yet there lacks cell carriers with these combined properties. In this work, we have developed a family of high oxygen preservation and fast gelation hydrogels based on N-isopropylacrylamide (NIPAAm) copolymers. The hydrogels were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization of NIPAAm, acrylate-oligolactide (AOLA), 2-hydroxyethyl methacrylate (HEMA), and methacrylate-poly(ethylene glycol)-perfluorooctane (MAPEGPFC). The hydrogel solutions exhibited sol-gel temperatures around room temperature and were flowable and injectable at 4°C. They can quickly solidify (≤6 s) at 37°C to form flexible gels. These hydrogels lost 9.4~29.4% of their mass after incubation in Dulbecco's Phosphate-Buffered Saline (DPBS) for 4 weeks. The hydrogels exhibited a greater oxygen partial pressure than DPBS after being transferred from a 21% O2 Condition to a 1% O2 Condition. When bone marrow mesenchymal stem cells (MSCs) were encapsulated in the hydrogels and cultured under 1% O2, the cells survived and proliferated during the 14-day culture period. In contrast, the cells experienced extensive death in the control hydrogel that had low oxygen preservation capability. The hydrogels possessed excellent biocompatibility. The final degradation products did not provoke cell death even when the concentration was as high as 15 mg/ml, and the hydrogel implantation did not induce substantial inflammation. These hydrogels are promising as cell carriers for cell transplantation into ischemic tissues. Statement of Significance Stem cell therapy for ischemic tissues experiences low therapeutic efficacy largely due to poor cell survival under low oxygen Condition. Using cell carriers with high oxygen preservation capability has potential to improve cell survival. In this work, we have developed a family of hydrogels with this property. These hydrogels promoted the encapsulated stem cell survival and growth under low oxygen Condition.
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an oxygen release system to augment cardiac progenitor cell survival and differentiation under Hypoxic Condition
Biomaterials, 2012Co-Authors: Xiaolei Guo, Jianjun GuanAbstract:Abstract Stem cell therapy has the potential to regenerate heart tissue damaged by myocardial infarction (MI), but it experiences extremely low efficacy. One of the major causes is the inferior cell survival under Hypoxic Condition of the infarcted hearts. We examined whether an oxygen-releasing system capable of sustainedly supplying oxygen to stem cells would augment cell survival and cardiac differentiation under Hypoxic Condition mimicking that of the infarcted hearts. The oxygen-releasing system consisted of hydrogen peroxide (H 2 O 2 )-releasing microspheres, catalase and an injectable, thermosensitive hydrogel. The microspheres were based on poly(lactide-co-glycolide) (PLGA) and a complex of H 2 O 2 and poly(2-vinlypyrridione) (PVP). The oxygen was generated after the released H 2 O 2 was decomposed by catalase. The hydrogel was designed to improve the retention of microspheres and stem cells in the beating heart tissue during myocardial injection. The oxygen-releasing system was capable of sustainedly releasing oxygen for at least two weeks. The release kinetics was dependent on the ratio of H 2 O 2 /VP. The hydrogel was based on N-isopropylacrylamide (NIPAAm), acrylic acid (AAc), and a macromer hydroxyethyl methacrylate-oligo(hydroxybutyrate) (HEMA-oHB). The hydrogel had a stiffness matching that of the heart tissue and was able to stimulate the cardiosphere-derived cells (CDCs) to differentiate into cardiomyocytes. Under Hypoxic Condition mimicking that of the infarcted hearts (1% O 2 ), CDCs encapsulated in the hydrogel experienced massive cell death. Introduction of oxygen release in the hydrogel significantly augmented cell survival; no cell death was found after seven days of culture, and cells even grew after seven days. Under Hypoxic Condition, cardiac differentiation of CDCs was completely silenced in the hydrogel, as confirmed at both mRNA and protein levels. However, introduction of oxygen release restored the differentiation. These results demonstrate that the developed oxygen-releasing system has great potential to improve the efficacy of cardiac stem cell therapy.
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differential roles of hypoxia inducible factor subunits in multipotential stromal cells under Hypoxic Condition
Journal of Cellular Biochemistry, 2011Co-Authors: Kenichi Tamama, Haruhisa Kawasaki, Svetoslava S Kerpedjieva, Jianjun Guan, Ramesh K Ganju, Chandan K SenAbstract:Cell therapy with bone marrow multipotential stromal cells (MSCs) represents a promising approach to promote wound healing and tissue regeneration. MSCs expanded in vitro lose early progenitors with differentiation and therapeutic potentials under normoxic Condition, whereas Hypoxic Condition promotes MSC self-renewal through preserving colony forming early progenitors and maintaining undifferentiated phenotypes. Hypoxia inducible factor (HIF) pathway is a crucial signaling pathway activated in Hypoxic Condition. We evaluated the roles of HIFs in MSC differentiation, colony formation, and paracrine activity under Hypoxic Condition. Hypoxic Condition reversibly decreased osteogenic and adipogenic differentiation. Decrease of osteogenic differentiation depended on HIF pathway; whereas decrease of adipogenic differentiation depended on the activation of unfolded protein response (UPR), but not HIFs. Hypoxia-mediated increase of MSC colony formation was not HIF-dependent also. Hypoxic exposure increased secretion of VEGF, HGF, and basic FGF in a HIF-dependent manner. These findings suggest that HIF has a limited, but pivotal role in enhancing MSC self-renewal and growth factor secretions under Hypoxic Condition.
Jongil Kim - One of the best experts on this subject based on the ideXlab platform.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1α and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1alpha and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.
Hyeonok Jin - One of the best experts on this subject based on the ideXlab platform.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1α and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1alpha and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.
Guojie Gao - One of the best experts on this subject based on the ideXlab platform.
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autophagy regulates the apoptosis of bone marrow derived mesenchymal stem cells under Hypoxic Condition via amp activated protein kinase mammalian target of rapamycin pathway
Cell Biology International, 2016Co-Authors: Zheng Zhang, Ming Yang, Yabin Wang, Le Wang, Zhitao Jin, Liping Ding, Lijuan Zhang, Lina Zhang, Wei Jiang, Guojie GaoAbstract:Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been demonstrated as an ideal autologous stem cells source for cell-based therapy for myocardial infarction (MI). However, poor viability of donor stem cells after transplantation limits their therapeutic efficiency, whereas the underlying mechanism is still poorly understood. Autophagy, a highly conserved process of cellular degradation, is required for maintaining homeostasis and normal function. Here, we investigated the potential role of autophagy on apoptosis in BM-MSCs induced by Hypoxic injury. BM-MSCs, isolated from male C57BL/6 mice, were subjected to hypoxia and serum deprivation (H/SD) injury for 6, 12, and 24 h, respectively. The autophagy state was regulated by 3-methyladenine (3MA) and rapamycin administration. Furthermore, compound C was administrated to inhibit AMPK. The apoptosis induced by H/SD was determined by TUNEL assays. Meanwhile, autophagy was measured by GFP-LC3 plasmids transfection and transmission electron microscope. Moreover, protein expressions were evaluated by Western blot assay. In the present study, we found that Hypoxic stress increased autophagy and apoptosis in BM-MSCs time dependently. Meanwhile, hypoxia increased the activity of AMPK/mTOR signal pathway. Moreover, increased apoptosis in BM-MSCs under hypoxia was abolished by 3-MA, whereas was aggravated by rapamycin. Furthermore, the increased autophagy and apoptosis in BM-MSCs induced by hypoxia were abolished by AMPK inhibitor compound C. These data provide evidence that hypoxia induced AMPK/mTOR signal pathway activation which regulated the apoptosis and autophagy in BM-MSCs. Furthermore, the apoptosis of BM-MSCs under Hypoxic Condition was regulated by autophagy via AMPK/mTOR pathway.
Myungjin Park - One of the best experts on this subject based on the ideXlab platform.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1α and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.
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Hypoxic Condition and high cell density induced expression of redd1 is regulated by activation of hypoxia inducible factor 1alpha and sp1 through the phosphatidylinositol 3 kinase akt signaling pathway
Cellular Signalling, 2007Co-Authors: Hyeonok Jin, Hyungchahn Lee, Sanghyeok Woo, Sungkeum Seo, Taeboo Choe, Doohyun Yoo, Seungbum Lee, Su Jae Lee, Myungjin Park, Jongil KimAbstract:Abstract Redd1, a recently discovered stress-response gene, is regulated by hypoxia via hypoxia-inducible factor 1 (HIF-1) and by DNA damage via p53/p63; however, the signaling pathway by which its expression is induced by hypoxia has not been elucidated. In the present study, we demonstrated that the expression of Redd1 in response to hypoxia (1% O 2 ), hypoxia-mimetic agent, cobalt chloride (CoCl 2 ) and high cell density (HCD) requires coactivation of HIF-1α and Sp1. CoCl 2 and HCD induced the activation of HIF-1α and Sp1 in HeLa cells, and siRNAs targeting HIF-1α and Sp1 abrogated Redd1 expression. Inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 and by a dominant-negative PI3K mutant reduced the expression of Redd1 and activation of HIF-1α and Sp1 by CoCl 2 and HCD. Also, suppression of Akt activation blocked the expression of Redd1 and the activation of HIF-1α and Sp1 by CoCl 2 and HCD. Furthermore, we found that the induction of Redd1 expression by CoCl 2 can be mediated by activation of Sp1 in HIF-1α-deficient cells but that a higher level of Redd1 expression is achieved when these cells are transfected with HIF-1α. These results demonstrate that Hypoxic Condition-and HCD-induced expression of Redd1 is mediated by coactivation of Sp1 and HIF-1α downstream of the PI3K/Akt signaling pathway.