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Jakarta, Indonesia

Li X.,Brigham and Womens Hospital | Utomo A.,Brigham and Womens Hospital | Utomo A.,Stem Cell and Cancer Institute | Cullere X.,Brigham and Womens Hospital | And 5 more authors.
Cell Host and Microbe | Year: 2011

Resistance to fungal infections is attributed to engagement of host pattern-recognition receptors, notably the β-glucan receptor Dectin-1 and the integrin Mac-1, which induce phagocytosis and antifungal immunity. However, the mechanisms by which these receptors coordinate fungal clearance are unknown. We show that upon ligand binding, Dectin-1 activates Mac-1 to also recognize fungal components, and this stepwise process is critical for neutrophil cytotoxic responses. Both Mac-1 activation and Dectin-1- and Mac-1-induced neutrophil effector functions require Vav1 and Vav3, exchange factors for RhoGTPases. Mac-1- or Vav1,3-deficient mice have increased susceptibility to systemic candidiasis that is not due to impaired neutrophil recruitment but defective intracellular killing of C. albicans yeast forms, and Mac-1 or Vav1,3 reconstitution in hematopoietic cells restores resistance. Our results demonstrate that antifungal immunity depends on Dectin-1-induced activation of Mac-1 functions that is coordinated by Vav proteins, a pathway that may localize cytotoxic responses of circulating neutrophils to infected tissues. © 2011 Elsevier Inc.

Widowati W.,Maranatha Christian University | Murti H.,Stem Cell and Cancer Institute | Jasaputra D.K.,Maranatha Christian University | Sumitro S.B.,Brawijaya University | And 4 more authors.
Asian Journal of Cell Biology | Year: 2016

Background: Breast cancer is one of the most common life threatening diseases worldwide and it is the leading cause of death from cancer in women. The effectiveness of current cancer therapies is low, even though it requires expensive cost. Therefore, the development of the more efficient therapy is highly needed. Objective: This research was conducted to evaluate the effect Tumour Necrosis Factor alpha (TNF-α) and Interferon gamma (IFN-γ) as anticancer agents against breast cancer cells (T47D, MCF7) and selectivity of cytotoxic effect towards human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) to produce hWJMSCs-Conditioned Medium (CM), hWJMSCs-Cell Lysate (CL) and hWJMSCs which potential used as anticancer candidates after induced by TNFα or IFNγ. Methodology: The hWJMSCs were isolated from umbilical cord and characterized by its surface marker phenotype and its multipotent differentiation potential. The breast cancer cell lines (T47D and MCF7) were treated by TNF-α and IFN-γ and its cytotoxic activity was observed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)- 2H-tetrazolium (MTS) viability assay. The cytotoxic effects of TNF-α and IFN-γ toward hWJMSCs were also observed using the same method. Results: Flow cytometry analysis showed that hWJMSCs for early passage (P4) were positive for hMSCs marker CD105, CD73 and negative for CD34, CD45, CD14, CD19 and HLA-II. It also showed the osteogenic, adipogenic and chondrogenic differentiation. The effect of TNF-α and IFN-γ against MCF7 cells exhibited that the cytokines decreased the cell viability in a dose dependent manner. The IC50 value of TNF-α and IFN-γ against breast cancer cell lines were found higher for T47D than MCF7. Conclusion: The TNF-α and IFN-γ inhibit the cell growth of breast cancer cells due to apoptotic or necrotic cells but it non-toxic against hWJMSCs. © 2016 Wahyu Widowati et al.

Widowati W.,Maranatha Christian University | Jasaputra D.K.,Maranatha Christian University | Sumitro S.B.,Brawijaya University | Widodo M.A.,Brawijaya University | And 2 more authors.
Immunology, Endocrine and Metabolic Agents in Medicinal Chemistry | Year: 2015

Cancer is one the most common life-threatening diseases. Cancer cases worldwide are forecast to rise by 75% in the future. Although cancer therapies have been improved, many tumors remain unresponsive to conventional treatments, such as radiation and chemotherapy. Therefore, novel strategies in treating and managing the disease are urgently needed. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently been shown to possess anti-cancer activities as well as tumor-homing ability. These cells are able to migrate to sites of neoplastic growth in vivo and their secretory products display tumoricidal activity both in vitro and in vivo models of human cancer. Recent reports also suggest that the anti-cancer potential of WJ-MSCs can also be enhanced through genetic engineering. This review will summarize the current understanding on the interactions between WJ-MSCs and tumor cells, as well as the potential use of both un-engineered and engineered WJ-MSCs as an anti-cancer agent. © 2015 Bentham Science Publishers.

Low J.T.,Walter and Eliza Hall Institute of Medical Research | Low J.T.,University of Melbourne | Hughes P.,Royal Melbourne Hospital | Lin A.,Walter and Eliza Hall Institute of Medical Research | And 13 more authors.
Immunology and Cell Biology | Year: 2016

Defects in apoptosis can cause autoimmune disease. Loss-of-function mutations in the 'death receptor' FAS impair the deletion of autoreactive lymphocytes in the periphery, leading to progressive lymphadenopathy and systemic lupus erythematosus-like autoimmune disease in mice (Faslpr/lpr (mice homozygous for the lymphoproliferation inducing spontaneous mutation)) and humans. The REL/nuclear factor-κB (NF-κB) transcription factors regulate a broad range of immune effector functions and are also implicated in various autoimmune diseases. We generated compound mutant mice to investigate the individual functions of the NF-κB family members NF-κB1, NF-κB2 and c-REL in the various autoimmune pathologies of Faslpr/lpr mutant mice. We show that loss of each of these transcription factors resulted in amelioration of many classical features of autoimmune disease, including hypergammaglobulinaemia, anti-nuclear autoantibodies and autoantibodies against tissue-specific antigens. Remarkably, only c-REL deficiency substantially reduced immune complex-mediated glomerulonephritis and extended the lifespan of Faslpr/lpr mice. Interestingly, compared with the Faslpr/lpr animals, Faslpr/lpr nfkb2-/- mice presented with a dramatic acceleration and augmentation of lymphadenopathy that was accompanied by severe lung pathology due to extensive lymphocytic infiltration. The Faslpr/lpr nfkb1-/- mice exhibited the combined pathologies caused by defects in FAS-mediated apoptosis and premature ageing due to loss of NF-κB1. These findings demonstrate that different NF-κB family members exert distinct roles in the development of the diverse autoimmune and lymphoproliferative pathologies that arise in Faslpr/lpr mice, and suggest that pharmacological targeting of c-REL should be considered as a strategy for therapeutic intervention in autoimmune diseases. © 2016 Australasian Society for Immunology Inc. All rights reserved.

Widowati W.,Maranatha Christian University | Wijaya L.,Stem Cell and Cancer Institute | Bachtiar I.,Stem Cell and Cancer Institute | Gunanegara R.F.,Maranatha Christian University | And 4 more authors.
Biomarkers and Genomic Medicine | Year: 2014

Mesenchymal stem cells (MSCs) from Wharton's jelly have a higher proliferation rate and self-renewal capacity than adult tissue-derived MSCs. A low oxygen level or hypoxic condition is prevalent in the microenvironment of the stem cells in the early stages of development. Hypoxia can influence proliferation and differentiation of various stem/precursor cell populations. This research was conducted: to determine the proliferation rate and characteristics of human MSCs from Wharton's jelly in hypoxic and normoxic condition; to evaluate their character after MSCs are incubated in hypoxic and normoxic environment using surface markers including CD105, CD73, CD14, CD19, CD34, CD45, and HLA-II; and to evaluate the proliferation rate and number of MSCs at many passages using the trypan blue method. The hypoxic and normoxic microenvironment showed significant differences in the proliferation rate and population doubling time, but and there were no differences in surface markers. © 2014.

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