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Sainte-Foy-lès-Lyon, France

Leeb C.,Ludwig Boltzmann Research Institute | Jurga M.,Cell Therapy Research Institute CTI LYON | McGuckin C.,Cell Therapy Research Institute CTI LYON | Moriggl R.,Ludwig Boltzmann Research Institute | And 2 more authors.
Stem Cell Reviews and Reports | Year: 2010

Recent findings have placed stem cell research at the forefront of biomedical sciences. Basic research on embryonic stem cells (ESCs) has contributed to our knowledge about the developmental potential and plasticity of stem cells. Furthermore, it has raised hope to use these cells as potential source for regenerative medicine and tissue replacement after injury or disease. Unfortunately, ESCs can also form tumors and they are ethically controversial because they originate from human embryos. This review summarizes findings and therapeutic applications of ESCs and their alternatives: adult stem cells and iPS cells. © Springer Science+Business Media, LLC 2009.

Leeb C.,Medical University of Vienna | Jurga M.,Cell Therapy Research Institute CTI LYON | Mcguckin C.,Cell Therapy Research Institute CTI LYON | Forraz N.,Cell Therapy Research Institute CTI LYON | And 4 more authors.
Cell Proliferation | Year: 2011

Although stem cell research is a rather new field in modern medicine, media soon popularized it. The reason for this hype lies in the potential of stem cells to drastically increase quality of life through repairing aging and diseased organs. Nevertheless, the essence of stem cell research is to understand how tissues are maintained during adult life. In this article, we summarize the various types of stem cells and their differentiation potential in vivo and in vitro. We review current clinical applications of stem cells and highlight problems encountered when going from animal studies to clinical practice. Furthermore, we describe the current state of induced pluripotent stem cell technology and applications for disease modelling and cell replacement therapy. © 2011 Blackwell Publishing Ltd.

Jurga M.,Cell Therapy Research Institute CTI LYON | Forraz N.,Cell Therapy Research Institute CTI LYON | Basford C.,Cell Therapy Research Institute CTI LYON | Basford C.,North East England Stem Cell Institute | And 8 more authors.
Stem Cells and Development | Year: 2012

Several innovative therapies with human umbilical cord blood stem cells (SCs) are currently developing to treat central nervous system (CNS) diseases. It has been shown that cord blood contains multipotent lineage-negative (LinNEG) SCs capable of neuronal differentiation. Clinically useful cord blood samples are stored in different biobanks worldwide, but the content and neurogenic properties of LinNEG cells are unknown. Here we have compared 5 major methods of blood processing: Sepax, Hetastarch, plasma depletion, Prepacyte-SC, and density gradient. We showed that Sepax-processed blood units contained 10-fold higher number of LinNEG cells after cryopreservation in comparison to all other methods. We showed in this study that multipotent SCs derived from fresh and frozen cord blood samples could be efficiently induced in defined serum-free medium toward neuronal progenitors (NF200+, Ki67+). During neuronal differentiation, the multipotent SCs underwent precise sequential changes at the molecular and cellular levels: Oct4 and Sox2 downregulation and Ngn1, NeuN, and PSD95 upregulation, similar to neurogenesis process in vivo. We expect that data presented here will be valuable for clinicians, researchers, biobanks, and patients and will contribute for better efficacy of future clinical trials in regeneration of CNS. © 2012 Mary Ann Liebert, Inc.

McGuckin C.P.,Cell Therapy Research Institute CTI LYON | Jurga M.,Cell Therapy Research Institute CTI LYON | Miller A.-M.,Trinity College Dublin | Sarnowska A.,Polish Academy of Sciences | And 15 more authors.
Archives of Biochemistry and Biophysics | Year: 2013

Increasing global birth rate, coupled with the aging population surviving into their eighth decade has lead to increased incidence diseases, hitherto designated as rare. Brain related ischemia, at birth, or later in life, during, for example stroke, is increasing in global prevalence. Reactive microglia can contribute to neuronal damage as well as compromising transplantion. One potential treatment strategy is cellular therapy, using mesenchymal stem cells (hMSCs), which possess immunomodulatory and cell repair properties. For effective clinical therapy, mechanisms of action must be understood better. Here multicentre international laboratories assessed this question together investigating application of hMSCs neural involvement, with interest in the role of reactive microglia. Modulation by hMSCs in our in vivo and in vitro study shows they decrease markers of microglial activation (lower ED1 and Iba) and astrogliosis (lower GFAP) following transplantation in an ouabain-induced brain ischemia rat model and in organotypic hippocampal cultures. The anti-inflammatory effect in vitro was demonstrated to be CD200 ligand dependent with ligand expression shown to be increased by IL-4 stimulation. hMSC transplant reduced rat microglial STAT3 gene expression and reduced activation of Y705 phosphorylated STAT3, but STAT3 in the hMSCs themselves was elevated upon grafting. Surprisingly, activity was dependent on heterodimerisation with STAT1 activated by IL-4 and Oncostatin M. Our study paves the way to preclinical stages of a clinical trial with hMSC, and suggests a non-canonical JAK-STAT signaling of unphosphorylated STAT3 in immunomodulatory effects of hMSCs. © 2012 Elsevier Inc. All rights reserved.

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