The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases
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...
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/431 |
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| author | Zyrafete Kuҫi Christiane Jordan Sibylle Wehner Jan Sörensen Andrea Jarisch Emilia Salzmann-Manrique Lisa-Marie Pfeffermann Thomas Klingebiel Peter Bader Selim Kuҫi |
| author_facet | Zyrafete Kuҫi Christiane Jordan Sibylle Wehner Jan Sörensen Andrea Jarisch Emilia Salzmann-Manrique Lisa-Marie Pfeffermann Thomas Klingebiel Peter Bader Selim Kuҫi |
| author_sort | Zyrafete Kuҫi |
| collection | DOAJ |
| description | 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 (<i>P</i> < 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 × 10<sup>6</sup> BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (<i>P</i> < 0.013) and control group (<i>P</i> < 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. |
| first_indexed | 2024-03-12T10:37:41Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T10:37:41Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6432bdc507ea43d68b23340bfbe5be302023-09-02T08:34:18ZengMDPI AGCells2073-44092020-02-019243110.3390/cells9020431cells9020431The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological DiseasesZyrafete Kuҫi0Christiane Jordan1Sibylle Wehner2Jan Sörensen3Andrea Jarisch4Emilia Salzmann-Manrique5Lisa-Marie Pfeffermann6Thomas Klingebiel7Peter Bader8Selim Kuҫi9University Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyInstitute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen GmbH, Goethe University Hospital, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyInstitute for Transfusion Medicine and Immunohaematology, German Red Cross Blood Donor Service Baden-Württemberg-Hessen GmbH, Goethe University Hospital, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyUniversity Hospital for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, Goethe University Frankfurt am Main, 60528 Frankfurt am Main, GermanyAs 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 (<i>P</i> < 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 × 10<sup>6</sup> BM-MNCs of patients with sickle cell disease (SCD) were generated significantly more CFU-Fs than from TM-BM-MNCs (<i>P</i> < 0.013) and control group (<i>P</i> < 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.https://www.mdpi.com/2073-4409/9/2/431mesenchymal stromal cellsnon-malignant hematological diseasesthalassemiasickle cell anemiasevere congenital neutropenia |
| spellingShingle | Zyrafete Kuҫi Christiane Jordan Sibylle Wehner Jan Sörensen Andrea Jarisch Emilia Salzmann-Manrique Lisa-Marie Pfeffermann Thomas Klingebiel Peter Bader Selim Kuҫi The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases Cells mesenchymal stromal cells non-malignant hematological diseases thalassemia sickle cell anemia severe congenital neutropenia |
| title | The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases |
| title_full | The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases |
| title_fullStr | The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases |
| title_full_unstemmed | The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases |
| title_short | The Phenotype and Functional Activity of Mesenchymal Stromal Cells in Pediatric Patients with Non-Malignant Hematological Diseases |
| title_sort | phenotype and functional activity of mesenchymal stromal cells in pediatric patients with non malignant hematological diseases |
| topic | mesenchymal stromal cells non-malignant hematological diseases thalassemia sickle cell anemia severe congenital neutropenia |
| url | https://www.mdpi.com/2073-4409/9/2/431 |
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