Mesenchymal and Hematopoyetic Stem Cells

Principal Investigator

Dr. César Trigueros Fernández
ctrigueros@inbiomed.org

Dr. Cesar Trigueros presents a well-established background in stem cell research, with several years of experience in the identification and differentiation of hematopoietic precursors. His studies began under the supervision of Dr Maria Luisa Toribio (CBMSO, CSIC, Madrid), focusing mostly in the study of the differentiation of several hematopoietic precursors cell lines present in the human thymus (T cells, dendritic cells, NK, etc). Following his research at Dr. Mike Owen's laboratory (Cancer Research UK, London), where he developed several studies about the signalling pathways involved in the differentiation of progenitors murine cells into T cell lineage (alpha/beta versus gamma/delta). He continued to work at Dr. Victor Tybulewicz's laboratory (National Institute for Medical Research, London), where he studied the function of Vav oncogene in hematopoietic development. He has been working in Inbiomed since 2004.

Scientific interest

Hematopoietic stem cells (HSC) have the potential of unlimited self-renewal (or at least throughout an important part of a person's life ) and the capacity of differentiation into all mature cells present in the blood. Allogenic or autologus HSC transplants have been widely used as treatment for neoplasias, haematological, immunodeficient and metabolic diseases in adults and children alike. Although historically, the bone marrow has been the main source of HSC, an alternative source of HSC has been described: the umbilical cord blood. Due to the HSC potential in transplants development, as well as the regeneration and reparation of any other tissues, research and development of these precursors is important. Although it is clear the advantages of using these stem cells, there are still some areas that require a more precise study in order to use these cells for more extensive purposes.

Mesenchymal stem cells (MSC) are multipotent cells present in a variety of tissues during development and therefore can be isolated from several, perhaps most, adult tissues, although bone marrow represents the source most often used. The recognition of the therapeutic potential of MSCs is likely the most exciting recent advance in cell therapy following the widespread use of HSC transplantation, which has been around for over forty years. The potential clinical use of MSCs in tissue repair mainly involves bone, cartilage and tendon.

Our main project is divided into two sections. Firstly, we are studying the processes implicated in the differentiation and expansion of HSC nad MSC obtained from umbilical cord blood and/or bone marrow. Secondly, we are evaluating the function of different genes in the maintenance of HSC and MSC phenotype.

Staff

PhD students:
Akaitz Dorronso
Naiara Tejados

Postdocs students:
Carina Elizalde
Jon Fernández

Technitians:
Izaskun Ferrin
Juan Manuel Salcedo

Publications

Ana Armiñán, Carolina Gandía, J. Manuel García-Verdugo, Elisa Lledó, César Trigueros, Amparo Ruiz-Saurí, Mª Dolores Miñana, Pilar Solves, Rafael Payá, J. Anastasio Montero, Pilar Sepúlveda. Mesenchymal stem cell provide better results than hematopoietic precursors for the treatment of myocardial infartaction. Journal of the American College of Cardilogy (JACC). in press Fecha: 2010.
José L Sardina, Guillermo López-Ruano, Luis I Sánchez-Abarca, José Antonio Pérez-Simón, Ainhoa Gaztelumendi, César Trigueros, Marcial Llanillo1, Jesús Sánchez-Yague, and Angel Hernández-Hernández. p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation. Cell Death and Differentiation. in press. 2010
Cárcamo-Orive I, Gaztelumendi A, Delgado J, Tejados N, Dorronsoro A, Fernandez-Rueda J, Pennington DJ, Trigueros C. Regulation of Human Bone Marrow Stromal Cell Proliferation and Differentiation Capacity by Glucocorticoid Receptor and AP-1 Cross-Talk. Journal of Bone and Mineral Research (JBMR). in press. 2010
De la Rosa O, Lombardo E, Beraza A, Mancheño^ P, Ramirez^ C, Menta^ R, Rico L, Camarillo E, García L, Trigueros C, Delgado M and Büscher D. Requirement of IFN-g mediated Indoleamine 2,3 dioxygenase expression in the modulation of lymphocyte proliferation by human adipose-derived stem cells.* *Submitted for publication. 2008
García-Castro J*, Trigueros C*, Madrenas J, Pérez-Simón JA, Rodriguez R & Menendez P^. Mesenchymal Stem Cells and their use as cell replacement therapy and disease modeling tool. J. Cell. Mol. Med. 2008. 12(6B):2552-2565. * These two authors contributed equally to this work.
Cárcamo-Orive I, Tejados N, Delgado J, Gaztelumendi A, Otaegui D, Lang V, Trigueros C. ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential. Exp Cell Res. 2008. 314(8):1777-88.
Cárcamo-Orive I and Trigueros C. Células Madre Mesenquimales y Transplante hematopoyético. Methods and Findings in Exp and Clin Pharmacology. 2008 (Supl. 1): 3-6
Prisco A, Vanes L, Ruf S, Trigueros C and Tybulewicz V. Lineage-specific requirement for the PH domain of Vav1 in TCR signalling within CD4+ but not CD8+ T cells. Immunity. 2005. 23:263-274.
Trigueros C, Hozumi K, Silva-Santos B, Bruno L, Hayday AC, Owen M, and Pennington D. Pre-TCR signalling regulates IL-7R expression promoting thymocyte survival at the DN to DP transition. Eur. J. Immunology. 2003. 31:4917-4928.
Denzel A, Molinari M, Trigueros C, Martin JE, Velmurgan S, Brown S, Stamp G and Owen M. Early Postnatal Death and Motor Disorders in Mice Congenitally Deficient in Calnexin Expression. Mol. Cell Biol. 2002. 22:7398-7404
Carrasco YR, Ramiro AR, Trigueros C, de Yebenes VG, Garcia-Peydro M, Toribio ML. An Endoplasmic Reticulum Retention Function for the Cytoplasmic Tail of the Human Pre-T Cell Receptor (TCR) alpha Chain. Potential role in the regulation of cell surface pre-TCR expression levels. J. Exp. Med. 2001. 193:1045-58.
Trigueros, C., Ramiro, A.R., Carrasco, Y.R., de Yébenes, V.G., Albar, J.P. and Toribio, M.L. Identification of a late stage of small non-cycling pT-negative pre-T cells as immediate precursors of TCR thymocytes. J. Exp. Med. 1998. 188:1401-1412.
Trigueros, C., Márquez, C., Muñoz, J., Ramiro, A.R., Carrasco, Y.R., López-Botet, M. and Toribio, M.L. Identification of a common developmental pathway for thymic natural killer cells and dendritic cells. Blood. 1998. 91(8):2760-2771.
Ramiro, A.R., de Yébenes, V.G., Trigueros, C., Carrasco, Y.R. and Toribio, M.L. Enhanced Green Fluorescent Protein as an efficient reporter gene for retroviral transduction of human multipotent lymphoid precursors. Hum. Gene Ther. 1998. 9:1103-1109.
Trigueros, C., Ramiro, A.R., Márquez, C., San Millán , J.L. and Toribio, M.L. Regulation of pre-T cell receptor (pT-TCR) gene expression during human thymic development. J. Exp. Med. 1996. 184:519-530.
Pacheco-Castro, A., Márquez, C., Toribio, M.L., Ramiro, A.R., Trigueros, C. and Regueiro, J.R. Herpervirus Saimiri immortalization of  and  human T-linage cells derived from CD34+ intrathymic precursors. Int. Immunol. 1996. 8:1797-1805.