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Yulyana Y.,Cancer Therapy and Research Center | Ho I.A.W.,Cancer Therapy and Research Center | Sia K.C.,Cancer Therapy and Research Center | Newman J.P.,Cancer Therapy and Research Center | And 16 more authors.
Molecular Therapy | Year: 2015

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world. The multikinase inhibitor sorafenib only demonstrated marginal improvement in overall survival for advanced disease prompted the search for alternative treatment options. Human mesenchymal stem cells (MSCs) have the ability to home to tumor cells. However, its functional roles on the tumor microenvironment remain controversial. Herein, we showed that conditioned media derived from human fetal MSC (CM-hfMSCs) expressed high level of the insulin growth factor binding proteins IGFBPs and can sequester free insulin-like growth factors (IGFs) to inhibit HCC cell proliferation. The inhibitory effect of IGFBPs on IGF signaling was further evident from the reduction of activated IGF-1R and PI3K/Akt, leading eventually to the induction of cell cycle arrest. We also demonstrated that CM-hfMSCs could enhance the therapeutic efficacy of sorafenib and sunitinib. To the best of our knowledge, this is the first report to show that CM-hfMSCs has a tumor-specific, antiproliferative effect that is not observed with normal human hepatocyte cells and patient-derived matched normal tissues. Our results thus suggest that CM-hfMSCs can provide a useful tool to design alternative/adjuvant treatment strategies for HCC, especially in related function to potentiate the effects of chemotherapeutic drugs. © 2015 The American Society of Gene & Cell Therapy.

Danieli P.,Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology | Danieli P.,Laboratory of Experimental Cardiology for Cell and Molecular Therapy | Malpasso G.,Coronary Care Unit and Laboratory of Clinical and Experimental Cardiology | Malpasso G.,Laboratory of Experimental Cardiology for Cell and Molecular Therapy | And 22 more authors.
Stem Cells Translational Medicine | Year: 2015

The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardio-protection and angiogenesis. Moreover, we aimed to identify the putative active paracrine medi-ators.hAMCswereisolated,expanded,andcharacterized.Invitro,conditionedmediumfromhAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, andstrongly promoted capillary formation at theinfarct border zone. Genearray analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factorswere detected in hAMC-CMbycytokine array.Ourresultsstronglysupport theconcept thattheadministrationof hAMC-CM favors the repair process after acute myocardial infarction. © Alpha Med Press 2015.

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