Abstract
As the biology of mesenchymal stromal cells (MSCs) in patients with non-malignant hematological diseases (NMHD) is poorly understood, in the current study we performed a basic characterization of the phenotype and functional activity of NMHD-MSCs. Bone marrow (BM) of patients with thalassemia major (TM) possessed a significantly higher number of nucleated cells (BM-MNCs)/mL BM than healthy donors (P < 0.0001), which however did not result in a higher number of colony forming units-fibroblast (CFU-F) per milliliter BM. In contrast, from 1 × 106 BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (P < 0.013) and control group (P < 0.02). In addition, NMHD-MSCs expressed significantly lower levels of CD146 molecule, demonstrated an equal proliferation potential and differentiated along three lineages (osteoblasts, chondrocytes and adipocytes) as healthy donors’ MSCs, with exception of TM-MSCs which differentiated weakly in adipocytes. In contrast to other NMHD-MSCs and healthy donors’ MSCs, TM-MSCs demonstrated an impaired in vitro immunosuppressive potential, either. Noteworthy, the majority of the immunosuppressive effect of NMHD-MSCs was mediated through prostaglandin-E2 (PGE2), because indomethacin (an inhibitor of PGE2 synthesis) was able to significantly reverse this effect. Our results indicate therefore that NMHD-MSCs, except TM-MSCs, may be used as an autologous cell-based therapy for post-transplant complications such as graft failure, graft-versus-host disease (GvHD) and osteonecrosis.
Highlights
Hematopoietic stem cell transplantation (HSCT) is the only effective treatment for a broad range of malignant and non-malignant hematological diseases such as severe form of beta thalassemia major (TM), sickle cell disease (SCD) and severe form of congenital neutropenia (SCN)
Mesenchymal Stromal Cells (MSCs) generated from the bone marrow of 21 healthy donors with a median age of 12 years, using a protocol approved by the University of Frankfurt Institutional Review Board
In contrast to MSCs generated from patients with aplastic anemia (AA), which have been thoroughly investigated [22,23,24,25,26,27,28], MSCs from patients with thalassemia and SCD are poorly characterized [29,30,31,32,33,34,35], whereas MSCs generated from patients with congenital neutropenia are not studied at all
Summary
Hematopoietic stem cell transplantation (HSCT) is the only effective treatment for a broad range of malignant and non-malignant hematological diseases such as severe form of beta thalassemia major (TM), sickle cell disease (SCD) and severe form of congenital neutropenia (SCN). Transplantation with hematopoietic stem cells of HLA-identical siblings is much more successful but as for only 25–40% of patients an HLA-identical sibling donor can be found [1] the other option remains transplantation of allogeneic hematopoietic stem cells. This kind of transplantation may be followed by many. About 29–42% of patients with SCD, thalassemia and SCN depending on the patients’ age and source of hematopoietic stem cells develop GvHD after transplantation [2,3,4,5]
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