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

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Summary

Introduction

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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