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The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases

1
University Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, Germany
2
Institute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen GmbH, Goethe University Hospital, 60528 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(2), 431; https://doi.org/10.3390/cells9020431 (registering DOI)
Received: 16 January 2020 / Revised: 7 February 2020 / Accepted: 7 February 2020 / Published: 12 February 2020
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.
Keywords: mesenchymal stromal cells; non-malignant hematological diseases; thalassemia; sickle cell anemia; severe congenital neutropenia mesenchymal stromal cells; non-malignant hematological diseases; thalassemia; sickle cell anemia; severe congenital neutropenia
MDPI and ACS Style

Kuci, Z.; Jordan, C.; Wehner, S.; Sörensen, J.; Jarisch, A.; Salzmann-Manrique, E.; Pfeffermann, L.-M.; Klingebiel, T.; Bader, P.; Kuҫi, S. The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases. Cells 2020, 9, 431.

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