Cargando…

Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union

Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspir...

Descripción completa

Detalles Bibliográficos
Autores principales: El-Jawhari, Jehan J., Kleftouris, George, El-Sherbiny, Yasser, Saleeb, Hany, West, Robert M., Jones, Elena, Giannoudis, Peter V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874596/
https://www.ncbi.nlm.nih.gov/pubmed/31758052
http://dx.doi.org/10.1038/s41598-019-53927-3
_version_ 1783472868835721216
author El-Jawhari, Jehan J.
Kleftouris, George
El-Sherbiny, Yasser
Saleeb, Hany
West, Robert M.
Jones, Elena
Giannoudis, Peter V.
author_facet El-Jawhari, Jehan J.
Kleftouris, George
El-Sherbiny, Yasser
Saleeb, Hany
West, Robert M.
Jones, Elena
Giannoudis, Peter V.
author_sort El-Jawhari, Jehan J.
collection PubMed
description Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271(high)CD45(low) cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271(high)CD45(low) cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing.
format Online
Article
Text
id pubmed-6874596
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-68745962019-12-04 Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union El-Jawhari, Jehan J. Kleftouris, George El-Sherbiny, Yasser Saleeb, Hany West, Robert M. Jones, Elena Giannoudis, Peter V. Sci Rep Article Bone marrow-Multipotential stromal cells (BM-MSCs) are increasingly used to treat complicated fracture healing e.g., non-union. Though, the quality of these autologous cells is not well characterized. We aimed to evaluate bone healing-related capacities of non-union BM-MSCs. Iliac crest-BM was aspirated from long-bone fracture patients with normal healing (U) or non-united (NU). Uncultured (native) CD271highCD45low cells or passage-zero cultured BM-MSCs were analyzed for gene expression levels, and functional assays were conducted using culture-expanded BM-MSCs. Blood samples were analyzed for serum cytokine levels. Uncultured NU-CD271highCD45low cells significantly expressed fewer transcripts of growth factor receptors, EGFR, FGFR1, and FGRF2 than U cells. Significant fewer transcripts of alkaline phosphatase (ALPL), osteocalcin (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were detected in NU-CD271(high)CD45(low) cells. Additionally, immunoregulation-related markers were differentially expressed between NU- and U-CD271(high)CD45(low) cells. Interestingly, passage-zero NU BM-MSCs showed low expression of immunosuppressive mediators. However, culture-expanded NU and U BM-MSCs exhibited comparable proliferation, osteogenesis, and immunosuppression. Serum cytokine levels were found similar for NU and U groups. Collectively, native NU-BM-MSCs seemed to have low proliferative and osteogenic capacities; therefore, enhancing their quality should be considered for regenerative therapies. Further research on distorted immunoregulatory molecules expression in BM-MSCs could potentially benefit the prediction of complicated fracture healing. Nature Publishing Group UK 2019-11-22 /pmc/articles/PMC6874596/ /pubmed/31758052 http://dx.doi.org/10.1038/s41598-019-53927-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
El-Jawhari, Jehan J.
Kleftouris, George
El-Sherbiny, Yasser
Saleeb, Hany
West, Robert M.
Jones, Elena
Giannoudis, Peter V.
Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title_full Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title_fullStr Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title_full_unstemmed Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title_short Defective Proliferation and Osteogenic Potential with Altered Immunoregulatory phenotype of Native Bone marrow-Multipotential Stromal Cells in Atrophic Fracture Non-Union
title_sort defective proliferation and osteogenic potential with altered immunoregulatory phenotype of native bone marrow-multipotential stromal cells in atrophic fracture non-union
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874596/
https://www.ncbi.nlm.nih.gov/pubmed/31758052
http://dx.doi.org/10.1038/s41598-019-53927-3
work_keys_str_mv AT eljawharijehanj defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT kleftourisgeorge defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT elsherbinyyasser defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT saleebhany defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT westrobertm defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT joneselena defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion
AT giannoudispeterv defectiveproliferationandosteogenicpotentialwithalteredimmunoregulatoryphenotypeofnativebonemarrowmultipotentialstromalcellsinatrophicfracturenonunion