This thesis describes the clinical use and laboratory findings of bone marrow (BM) derived, ex-vivo expanded human Mesenchymal Stromal Cells (MSCs) in pediatric stem cell transplantation. Advances... Show moreThis thesis describes the clinical use and laboratory findings of bone marrow (BM) derived, ex-vivo expanded human Mesenchymal Stromal Cells (MSCs) in pediatric stem cell transplantation. Advances in transplant technologies have permitted the use of __alternative donors__, i.e. haploidentical peripheral blood stem cells and umbilical cord blood, as a source of donor hematopoietic stem cells. MSCs located in the bone marrow form the stromal network, essential for the support of normal hematopoietic stem cell growth and development. Methods to expand MSCs sufficient for clinical uses have recently become available. In vitro experiments show MSCs interact with various cells of both the innate and adaptive immune system, which overall results in the induction of an anti-inflammatory state. The ability of MSCs to support hematopoietic stem cell growth coupled with their potent immune suppressive effects mean that they are ideal candidate cells to explore in the context of overcoming some of the problems specifically associated with the use of alternative donors. In this thesis, we therefore attempted to address the most relevant of these issues that, given the known properties of MSCs, would allow us to assess the possible usefulness of MSCs as an innovative strategy to resolve them. Show less
