Vrije Universiteit Brussel

 

Bone marrow and peripheral blood stem cell therapy

Stem cells are undifferentiated cells that are capable of self-renewal and differentiation in mature functional cells. They are not only present during embryonic life (embryonic stem cells) but can also be identified in various tissues during adult life (adult stem cells). The adult stem cell type that has been best characterized until now is the haematopoietic stem cell (HSC). Haematopoietic stem cell transplantations (HSCT) are used for more than 20 years as standard therapy for treatment of patients with haematological malignancies or stem cell deficiencies.

For more than two decades, the research unit Hematology-Immunology (HEIM) studies biological features and clinical use of haematopoietic stem cells (HSC) for treatment of patients with malignant blood cell disorders. These research activities are directly linked to a clinical transplantation program UZ Brussel that is internationally accredited by the European Group of Blood and Marrow Transplantation (EBMT) and that includes so far more that 500 transplantation procedures. The HSC preparation, prior to clinical use, is performed in the stem cell laboratory UZ Brussel. This laboratory is equipped for processing and cryopreservation of HSC according to international standards of GLP (Good Laboratory Practice). All technical facilities for clinical scale isolation, freezing and quality control of HSC grafts are available. There is a direct collaboration with the laboratories Hematology-Immunology, HLA-typing and Molecular Haematology, UZ Brussel. Past and ongoing research studies are related to the phenotype of normal and malignant stem cells, identification of predictive parameters for clinical complications associated with allogeneic HSC grafting, in vitro manipulation of HSC grafts, role of NK cell antigens in the outcome of allogeneic HSCT and molecular detection of minimal residual disease.

Although HSC mostly produce mature blood cells, at least a subpopulation expresses the capacity for non-haematopoietic differentiation as well. Indeed, a subset of CD133+ HSC can differentiate in endothelial cells that form blood vessels. This feature, called stem cell plasticity, is also the hallmark of another adult, bone marrow-derived cell type, the mesenchymal stem cell (MSC). MSCs can differentiate in osteoblasts, chondrocytes, myocytes, tendocytes and adipocytes. More recently it was found that MSC can also differentiate into endothelial cells and neural cells. MSC have also the capacity to sustain the growth of HSC by secretion of various haematopoiesis-supporting cytokines.

Based on all these observations it is assumed that bone marrow-derived multipotent adult stem cells can be therapeutically used for various types of tissue-regeneration, induction of blood vessel formation and as target cells for gene therapy in inborn or malignant disorders. Whereas CD133+ stem cells can directly be immuno-selected from bone marrow or from peripheral blood, MSC can be isolated from bone marrow by in vitro culture-expansion. Both techniques allow generating these adult stem cell types at levels sufficient for therapeutical administration. In the stem cell laboratory UZ Brussel, all technical facilities and conditions were established to prepare these multipotent stem cells for (pre-) clinical studies.

For clinical applications with adult multipotent stem cells, intravenous injection seems to be the simplest route of administration. However, the directed migration of intravenously injected stem cells to the targeted tissue implicates that these cells must be equipped with the appropriate mechanisms that allow transendothelial migration and tissue-directed homing. In the research unit HEIM, an ongoing research project aims to identify molecular mechanisms that mediate the extravasation and homing of culture-expanded MSC. In parallel, there is a study ongoing, in collaboration with the department cardiology UZ Brussel, to evaluate the homing properties of in vitro-selected CD133+ stem cells after intracoronary delivery in patients with chronic ischemic heart disease.


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  ©2004-2012 • HEIM • Vrije Universiteit Brussel • Faculteit Geneeskunde & Farmacie • Laarbeeklaan 103 • 1090 Jette • Tel.: (+32)-(0)2-477.44.06 • heim@vub.ac.be

12/08/10