1,721,329 research outputs found
Mesenchymal stromal cells: more than inhibitory cells
No full textMesenchymal stem cells, cautiously re-named recently multipotent mesenchymal stromal cells (MSCs) because of their heterogeneous multipotency at single cell level and their similarities with fibroblasts, have been strongly suggested in the last decade as powerful inhibitory cells for the vast majority of immune effector cells. The redundancy of the molecular pathways involved in the immune modulation suggests that this property, shared by MSCs of different tissue origin, including lymphoid organs, and by fibroblasts, has a pivotal role in tissue homeostasis in normal and pathological inflammatory reactions
Mesenchymal stromal cell ‘licensing’: a multistep process
No full textMany in vitro and in vivo data are available supporting the role of mesenchymal stromal cell (MSC) licensing in the induction of a measurable and effective immune regulation. The failure of some MSC-based protocols for immune modulation in animal models and in human clinical trials may be explained by either lack of a proper licensing by inflammatory microenviroment or wrong timing in MSC administration. Thus, optimization of MSC use for immune-regulating purposes is required to maximize their beneficial effects
The challenge of defining mesenchymal stromal cell potency assays and their potential use as release criteria
No full textCulture-expanded mesenchymal stromal cell (MSC)-like cells derived from marrow, adipose tissue or umbilical cord from either autologous or random donor sources are being studied in clinical trials across numerous regulatory jurisdictions worldwide (Figure 1). The ailments targeted with this cell pharmaceutical platform fall roughly within two categories: immune/inflammatory and tissue repair/ restoration. Across this spectrum of cell product and clinical indications, the interests of translational scientists and regulators intersect in best defining criteria for release and potency. The fairly well-established notions of sterility and cell viability (typically at least 70%) as release criteria are well accepted. The consensus onmarkers for identity of MSC-like cells is also reasonably well-defined. Thus, the minimum tripartite components of release criteria for cellular products in early-phase clinical trials—identity, viability and sterility—raise little practical controversy
Flow cytometry for minimal residual disease detection in acute lymphoblastic leukaemia
No full textFlow cytometry for minimal residual disease detection in acute lymphoblastic leukaemi
Human Bone Marrow and Adipose Tissue Mesenchymal Stem Cells: A User's Guide
No full textMesenchymal stem cells (MSCs) are adult stem cells that hold great promise in the field of regenerative medicine. They can be isolated from almost any tissue of the body and display, after expansion, very similar properties and minor differences, probably due to their microenvironment of origin. Expansion in vitro can be obtained in cytokine-free, serum-enriched media, as well as in serum-free, basic fibroblast growth factor-enriched media. A detailed immunophenotypic analysis is required to test the purity of the preparation, but no unique distinguishing marker has been described as yet. Functional assays, that is, differentiation studies in vitro, are needed to prove multilineage differentiation of expanded cells, and demonstration of pluripotency is necessary to identify most immature precursors. MSCs show powerful immunomodulative properties toward most of the cells of the immune system: this strengthens the theoretical rationale for their use also in an allogeneic setting across the major histocompatibility complex (MHC) immunological barriers. Systemic intravenous injection and local use have been tried: after systemic injection, MSCs show a high degree of chemotaxis based on pro-inflammatory cytokines, and localize at inflamed and neoplastic tissues; local regeneration has been improved using synthetic, as well as organic scaffolds. On the other hand, inadequate heterotopic in vivo differentiation and neoplastic transformation are potential risks of this form of cell therapy, even if evidence of this sort has been collected only from studies in mice, and generally after prolonged in vitro expansion. This review tries to provide a detailed technical overview of the methods used for human bone-marrow (BM)-derived and adipose-tissue (AT)-derived MSC isolation, in vitro expansion, and characterization for tissue repair. We chose to use BM-MSCs as a model to describe techniques that have been used for MSC isolation and expansion from very different sources, and AT-MSCs as an example of a reliable and increasingly common alternative source
Immunophenotypic measurable residual disease monitoring in adult acute lymphoblastic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation
Full text linkAllogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a survival benefit to adult patients affected by acute lymphoblastic leukemia (ALL). However, to avoid an overt disease relapse, patients with pre or post transplant persistence or occurrence of measurable residual disease (MRD) may require cellular or pharmacological interventions with eventual side effects. While the significance of multiparametric flow cytometry (MFC) in the guidance of ALL treatment in both adult and pediatric patients is undebated, fewer data are available regarding the impact of MRD monitoring, as assessed by MFC analysis, in the allo-HSCT settings. Aim of this article is to summarize and discuss currently available information on the role of MFC detection of MRD in adult ALL patients undergoing allo-HSCT. The significance of MFC-based MRD according to sensitivity level, timing, and in relation to molecular techniques of MRD and chimerism assessment will be also discussed
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