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NCBI pubmed
  • Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.
    Related Articles

    Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.

    Mar Drugs. 2017 Mar 01;15(3):

    Authors: Hong SC, Yoo SY, Kim H, Lee J

    Abstract
    Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives.

    PMID: 28257059 [PubMed - indexed for MEDLINE]

  • Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease.
    Related Articles

    Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease.

    Am J Physiol Gastrointest Liver Physiol. 2017 Apr 01;312(4):G348-G354

    Authors: Stamp LA

    Abstract
    Cell therapeutic approaches to treat a range of congenital and degenerative neuropathies are under intense investigation. There have been recent significant advancements in the development of cell therapy to treat disorders of the enteric nervous system (ENS), enteric neuropathies. These advances include the efficient generation of enteric neural progenitors from pluripotent stem cells and the rescue of a Hirschsprung disease model mouse following their transplantation into the bowel. Furthermore, a recent study provides evidence of functional innervation of the bowel muscle by neurons derived from transplanted ENS-derived neural progenitors. This mini-review discusses these recent findings, compares endogenous ENS-derived progenitors and pluripotent stem cell-derived progenitors as a cell source for therapy, and proposes the key steps for cell therapy to treat Hirschsprung disease.

    PMID: 28209600 [PubMed - indexed for MEDLINE]

  • Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet.
    Related Articles

    Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet.

    Transl Res. 2017 Apr;182:61-74.e8

    Authors: Lee CW, Hsiao WT, Lee OK

    Abstract
    Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice. All 3 MSC-based treatments improved obesity-associated metabolic syndromes including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, glucose intolerance, and inflammation in obese mice after repeated administration for 10 weeks. MSC-based treatments altered the ratio of adiponectin to leptin and regulated the expression of Pparα and Pparγ, which are involved in maintaining energy homeostasis, in major metabolic tissues. Among treatments, M-BA showed the strongest beneficial effect. Importantly, M-BA administration not only reduced obesity-associated metabolic syndromes but also reduced body weight and hyperlipidemia, indicating that it is an effective therapy for obesity. Together, our findings revealed the therapeutic potential of MSCs for the treatment of metabolic syndrome.

    PMID: 27908750 [PubMed - indexed for MEDLINE]

  • Telocytes in Chronic Inflammatory and Fibrotic Diseases.
    Related Articles

    Telocytes in Chronic Inflammatory and Fibrotic Diseases.

    Adv Exp Med Biol. 2016;913:51-76

    Authors: Ibba-Manneschi L, Rosa I, Manetti M

    Abstract
    Telocytes are a peculiar stromal (interstitial) cell type implicated in tissue homeostasis and development, as well as in the pathophysiology of several disorders. Severe damage and reduction of telocytes have been reported during fibrotic remodeling of multiple organs in various diseases, including scleroderma, Crohn's disease, ulcerative colitis, and liver fibrosis, as well as in chronic inflammatory lesions like those of primary Sjögren's syndrome and psoriasis. Owing to their close relationship with stem cells, telocytes are also supposed to contribute to tissue repair/regeneration. Indeed, telocytes are universally considered as "connecting cells" mostly oriented to intercellular signaling. On the basis of recent promising experimental findings, in the near future, telocyte transplantation might represent a novel therapeutic opportunity to control the evolution of chronic inflammatory and fibrotic diseases. Notably, there is evidence to support that telocytes could help in preventing abnormal activation of immune cells and fibroblasts, as well as in attenuating the altered matrix organization during the fibrotic process. By targeting telocytes alone or in tandem with stem cells, we might be able to promote regeneration and prevent the evolution to irreversible tissue injury. Besides exogenous transplantation, exploring pharmacological or non-pharmacological methods to enhance the growth and/or survival of telocytes could be an additional therapeutic strategy for many disorders.

    PMID: 27796880 [PubMed - indexed for MEDLINE]

  • Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow cells.
    Related Articles

    Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow cells.

    Innate Immun. 2016 Oct;22(7):493-502

    Authors: Zhao X, Cao M, Lu Z, Wang T, Ren Y, Liu C, Nelson D

    Abstract
    Sorafenib has been used for the treatment of liver cancer. However, its clinical impact on human immunity system remains poorly known. Our previous study has shown that sorafenib modulates immunosuppressive cell populations in murine liver cancer models. Here, we continue to report that low doses of sorafenib promotes the survival of murine bone marrow cells (BMCs) in a dose-dependent manner by up-regulating the anti-apoptotic protein survivin. Sorafenib induces differentiation of BMCs into suppressive dendritic cells that inhibit autologous T-cell proliferation and stimulate CD4(+) T cells to express increased IL-1β, IL-2, IL-4, IL-10, IFN-γ and TNF-α, and reduced levels of IL-6 and CD25, which indicates that sorafenib-induced dendritic cells represent a distinct cellular subset with unique properties. Taken together, our findings suggest that in addition to its anticancer effects, sorafenib has an immunoregulatory property that is apparent at low doses.

    PMID: 27440860 [PubMed - indexed for MEDLINE]

  • Human Herpesviruses 6A, 6B, and 7.
    Related Articles

    Human Herpesviruses 6A, 6B, and 7.

    Microbiol Spectr. 2016 Jun;4(3):

    Authors: Agut H, Bonnafous P, Gautheret-Dejean A

    Abstract
    Human roseoloviruses include three different species, human herpesviruses 6A, 6B, and 7 (HHV-6A, HHV-6B, HHV-7), genetically related to human cytomegalovirus. They exhibit a wide cell tropism in vivo and, like other herpesviruses, induce a lifelong latent infection in humans. In about 1% of the general population, HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6). Many active infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. They also may cause serious diseases, particularly in immunocompromised individuals, including hematopoietic stem-cell transplant (HSCT) and solid-organ transplant recipients, and acquired immunodeficiency syndrome (AIDS) patients. This opportunistic pathogenic role is formally established for HHV-6 infection and less clear for HHV-7. It mainly concerns the central-nervous system, bone marrow, lungs, gastrointestinal tract, skin, and liver. As the best example, HHV-6 causes both exanthema subitum, a benign disease associated with primary infection, and severe encephalitis associated with virus reactivations in HSCT recipients. Diagnosis using serologic and direct antigen-detection methods currently exhibits limitations. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time polymerase-chain reaction (PCR). The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active infections, but there is currently no consensus regarding the indications of treatment or specifics of drug administration. Numerous questions about HHV-6A, HHV-6B, HHV-7 are still pending, concerning in particular clinical impact and therapeutic options in immunocompromised patients.

    PMID: 27337451 [PubMed - indexed for MEDLINE]

pubmed: liver disease and st...
NCBI: db=pubmed; Term=liver disease and stem cell treatment
NCBI pubmed
  • Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.
    Related Articles

    Chitosan-Based Multifunctional Platforms for Local Delivery of Therapeutics.

    Mar Drugs. 2017 Mar 01;15(3):

    Authors: Hong SC, Yoo SY, Kim H, Lee J

    Abstract
    Chitosan has been widely used as a key biomaterial for the development of drug delivery systems intended to be administered via oral and parenteral routes. In particular, chitosan-based microparticles are the most frequently employed delivery system, along with specialized systems such as hydrogels, nanoparticles and thin films. Based on the progress made in chitosan-based drug delivery systems, the usefulness of chitosan has further expanded to anti-cancer chemoembolization, tissue engineering, and stem cell research. For instance, chitosan has been used to develop embolic materials designed to efficiently occlude the blood vessels by which the oxygen and nutrients are supplied. Indeed, it has been reported to be a promising embolic material. For better anti-cancer effect, embolic materials that can locally release anti-cancer drugs were proposed. In addition, a complex of radioactive materials and chitosan to be locally injected into the liver has been investigated as an efficient therapeutic tool for hepatocellular carcinoma. In line with this, a number of attempts have been explored to use chitosan-based carriers for the delivery of various agents, especially to the site of interest. Thus, in this work, studies where chitosan-based drug delivery systems have successfully been used for local delivery will be presented along with future perspectives.

    PMID: 28257059 [PubMed - indexed for MEDLINE]

  • Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease.
    Related Articles

    Cell therapy for GI motility disorders: comparison of cell sources and proposed steps for treating Hirschsprung disease.

    Am J Physiol Gastrointest Liver Physiol. 2017 Apr 01;312(4):G348-G354

    Authors: Stamp LA

    Abstract
    Cell therapeutic approaches to treat a range of congenital and degenerative neuropathies are under intense investigation. There have been recent significant advancements in the development of cell therapy to treat disorders of the enteric nervous system (ENS), enteric neuropathies. These advances include the efficient generation of enteric neural progenitors from pluripotent stem cells and the rescue of a Hirschsprung disease model mouse following their transplantation into the bowel. Furthermore, a recent study provides evidence of functional innervation of the bowel muscle by neurons derived from transplanted ENS-derived neural progenitors. This mini-review discusses these recent findings, compares endogenous ENS-derived progenitors and pluripotent stem cell-derived progenitors as a cell source for therapy, and proposes the key steps for cell therapy to treat Hirschsprung disease.

    PMID: 28209600 [PubMed - indexed for MEDLINE]

  • Protective roles of hepatic GABA signaling in acute liver injury of rats.
    Related Articles

    Protective roles of hepatic GABA signaling in acute liver injury of rats.

    Am J Physiol Gastrointest Liver Physiol. 2017 Mar 01;312(3):G208-G218

    Authors: Wang S, Xiang YY, Zhu J, Yi F, Li J, Liu C, Lu WY

    Abstract
    γ-Aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes. The function of hepatic GABA signaling system in rats was examined using models of d-galactosamine (GalN)-induced acute hepatocytic injury in vivo and in vitro. The expression of GAD increased whereas GABAAR subunits decreased in the liver of GalN-treated rats. Remarkably, treating rats with GABA or the GABAAR agonist muscimol, but not the GABABR agonist baclofen, protected hepatocytes against GalN toxicity and improved liver function. In addition, muscimol treatment decreased the formation of pseudobile ductules and the enlargement of hepatocytic canaliculi in GalN-treated rats. Our results revealed that a complex GABA signaling system exists in the rat liver. Activation of this intrahepatic GABAergic system protected the liver against toxic injury.NEW & NOTEWORTHY Auto- and paracrine GABAergic signaling systems exist in the rat hepatocytes and cholangiocytes. Activation of GABA signaling protects liver function from d-galactosamine injury by reducing toxic impairment of hepatocytes and by decreasing cholangiocyte proliferation.

    PMID: 27979827 [PubMed - indexed for MEDLINE]

  • Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet.
    Related Articles

    Mesenchymal stromal cell-based therapies reduce obesity and metabolic syndromes induced by a high-fat diet.

    Transl Res. 2017 Apr;182:61-74.e8

    Authors: Lee CW, Hsiao WT, Lee OK

    Abstract
    Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice. All 3 MSC-based treatments improved obesity-associated metabolic syndromes including nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, glucose intolerance, and inflammation in obese mice after repeated administration for 10 weeks. MSC-based treatments altered the ratio of adiponectin to leptin and regulated the expression of Pparα and Pparγ, which are involved in maintaining energy homeostasis, in major metabolic tissues. Among treatments, M-BA showed the strongest beneficial effect. Importantly, M-BA administration not only reduced obesity-associated metabolic syndromes but also reduced body weight and hyperlipidemia, indicating that it is an effective therapy for obesity. Together, our findings revealed the therapeutic potential of MSCs for the treatment of metabolic syndrome.

    PMID: 27908750 [PubMed - indexed for MEDLINE]

  • Telocytes in Chronic Inflammatory and Fibrotic Diseases.
    Related Articles

    Telocytes in Chronic Inflammatory and Fibrotic Diseases.

    Adv Exp Med Biol. 2016;913:51-76

    Authors: Ibba-Manneschi L, Rosa I, Manetti M

    Abstract
    Telocytes are a peculiar stromal (interstitial) cell type implicated in tissue homeostasis and development, as well as in the pathophysiology of several disorders. Severe damage and reduction of telocytes have been reported during fibrotic remodeling of multiple organs in various diseases, including scleroderma, Crohn's disease, ulcerative colitis, and liver fibrosis, as well as in chronic inflammatory lesions like those of primary Sjögren's syndrome and psoriasis. Owing to their close relationship with stem cells, telocytes are also supposed to contribute to tissue repair/regeneration. Indeed, telocytes are universally considered as "connecting cells" mostly oriented to intercellular signaling. On the basis of recent promising experimental findings, in the near future, telocyte transplantation might represent a novel therapeutic opportunity to control the evolution of chronic inflammatory and fibrotic diseases. Notably, there is evidence to support that telocytes could help in preventing abnormal activation of immune cells and fibroblasts, as well as in attenuating the altered matrix organization during the fibrotic process. By targeting telocytes alone or in tandem with stem cells, we might be able to promote regeneration and prevent the evolution to irreversible tissue injury. Besides exogenous transplantation, exploring pharmacological or non-pharmacological methods to enhance the growth and/or survival of telocytes could be an additional therapeutic strategy for many disorders.

    PMID: 27796880 [PubMed - indexed for MEDLINE]

  • Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow cells.
    Related Articles

    Small-molecule inhibitor sorafenib regulates immunoreactions by inducing survival and differentiation of bone marrow cells.

    Innate Immun. 2016 Oct;22(7):493-502

    Authors: Zhao X, Cao M, Lu Z, Wang T, Ren Y, Liu C, Nelson D

    Abstract
    Sorafenib has been used for the treatment of liver cancer. However, its clinical impact on human immunity system remains poorly known. Our previous study has shown that sorafenib modulates immunosuppressive cell populations in murine liver cancer models. Here, we continue to report that low doses of sorafenib promotes the survival of murine bone marrow cells (BMCs) in a dose-dependent manner by up-regulating the anti-apoptotic protein survivin. Sorafenib induces differentiation of BMCs into suppressive dendritic cells that inhibit autologous T-cell proliferation and stimulate CD4(+) T cells to express increased IL-1β, IL-2, IL-4, IL-10, IFN-γ and TNF-α, and reduced levels of IL-6 and CD25, which indicates that sorafenib-induced dendritic cells represent a distinct cellular subset with unique properties. Taken together, our findings suggest that in addition to its anticancer effects, sorafenib has an immunoregulatory property that is apparent at low doses.

    PMID: 27440860 [PubMed - indexed for MEDLINE]