Bone marrow mesenchymal stem cells from patients with aplastic anemia maintain functional and immune properties and do not contribute to the pathogenesis of the disease
Clara Bueno,
Mar Roldan,
Eduardo Anguita,
Damia Romero-Moya,
Beatriz Martín-Antonio,
Michael Rosu-Myles,
Consuelo del Cañizo,
Francisco Campos,
Regina García,
Maite Gómez-Casares,
Jose Luis Fuster,
Manuel Jurado,
Mario Delgado,
Pablo Menendez
Affiliations
Clara Bueno
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Faculty of Medicine, Barcelona, Spain
Mar Roldan
GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government, Granada, Spain
Eduardo Anguita
Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain
Damia Romero-Moya
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Faculty of Medicine, Barcelona, Spain
Beatriz Martín-Antonio
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Faculty of Medicine, Barcelona, Spain
Michael Rosu-Myles
Biologics and Genetic Therapies Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
Consuelo del Cañizo
Department of Hematology, University Hospital of Salamanca and Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain
Francisco Campos
Department of Neurology, Neurovascular Area, Clinical Neurosciences Research Laboratory, Hospital Clínico-Health Research Institute of Santiago de Compostela, Spain
Regina García
Servicio de Hematología, Hospital Clínico de Málaga, Málaga, Spain
Maite Gómez-Casares
Servicio de Hematología, Hospital Universitario Insular Materno-Infantil, Las Palmas de Gran Canaria, Spain
Jose Luis Fuster
Sección de Oncohematología Pediátrica, Hospital Virgen de Arrixaca, Murcia, Spain
Manuel Jurado
Servicio de Hematología, Hospital Universitario Virgen de las Nieves, Granada, Spain
Mario Delgado
Instituto de Parasitología y Biomedicina López-Neyra, CSIC, Granada, Spain
Pablo Menendez
Josep Carreras Leukemia Research Institute, Cell Therapy Program of the University of Barcelona, Faculty of Medicine, Barcelona, Spain;Instituciò Catalana de Reserca i Estudis Avançats (ICREA), Barcellona, Spain
Aplastic anemia is a life-threatening bone marrow failure disorder characterized by peripheral pancytopenia and marrow hypoplasia. The majority of cases of aplastic anemia remain idiopathic, although hematopoietic stem cell deficiency and impaired immune responses are hallmarks underlying the bone marrow failure in this condition. Mesenchymal stem/stromal cells constitute an essential component of the bone marrow hematopoietic microenvironment because of their immunomodulatory properties and their ability to support hematopoiesis, and they have been involved in the pathogenesis of several hematologic malignancies. We investigated whether bone marrow mesenchymal stem cells contribute, directly or indirectly, to the pathogenesis of aplastic anemia. We found that mesenchymal stem cell cultures can be established from the bone marrow of aplastic anemia patients and display the same phenotype and differentiation potential as their counterparts from normal bone marrow. Mesenchymal stem cells from aplastic anemia patients support the in vitro homeostasis and the in vivo repopulating function of CD34+ cells, and maintain their immunosuppressive and anti-inflammatory properties. These data demonstrate that bone marrow mesenchymal stem cells from patients with aplastic anemia do not have impaired functional and immunological properties, suggesting that they do not contribute to the pathogenesis of the disease.
