Cargando…

Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs

BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are impo...

Descripción completa

Detalles Bibliográficos
Autores principales: Somaiah, Chinnapaka, Kumar, Atul, Sharma, Renu, Sharma, Amit, Anand, Trishna, Bhattacharyya, Jina, Das, Damodar, Deka Talukdar, Sewali, Jaganathan, Bithiah Grace
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774172/
https://www.ncbi.nlm.nih.gov/pubmed/29351753
http://dx.doi.org/10.1186/s12929-018-0407-7
_version_ 1783293718404530176
author Somaiah, Chinnapaka
Kumar, Atul
Sharma, Renu
Sharma, Amit
Anand, Trishna
Bhattacharyya, Jina
Das, Damodar
Deka Talukdar, Sewali
Jaganathan, Bithiah Grace
author_facet Somaiah, Chinnapaka
Kumar, Atul
Sharma, Renu
Sharma, Amit
Anand, Trishna
Bhattacharyya, Jina
Das, Damodar
Deka Talukdar, Sewali
Jaganathan, Bithiah Grace
author_sort Somaiah, Chinnapaka
collection PubMed
description BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine. We also tested anti-cancer effects of drug treated MSC on leukemia cells. RESULTS: Treatment with the chemotherapeutic drugs resulted in functional defects in MSC, leading to reduced proliferation, osteogenic and adipogenic differentiation. The drug treated MSC also showed decreased expression of cell surface receptors, and the changes in proliferation, phenotype and differentiation defect was partially reversible after withdrawing the drugs from the cells. The drug treated MSC showed increased expression of cytokines, IL6, FGF2 and TNFA but reduced levels of differentiation markers SOX9 and ACTC1. Drug treated MSC also contributed to reduced anti-cancer effects in leukemia cells. CONCLUSIONS: Chemotherapeutic drug treatment altered the phenotype, osteogenic and adipogenic differentiation potential of MSC and modified the gene expression profile of the cells to render them more chemoprotective of the leukemic cells. Thus, additional therapeutic efforts to target the stromal cell population will help in preventing chemoresistance, disease relapse in leukemia and to maintain a healthy bone marrow stroma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0407-7) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-5774172
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-57741722018-01-26 Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs Somaiah, Chinnapaka Kumar, Atul Sharma, Renu Sharma, Amit Anand, Trishna Bhattacharyya, Jina Das, Damodar Deka Talukdar, Sewali Jaganathan, Bithiah Grace J Biomed Sci Research BACKGROUND: Mesenchymal stem cells (MSC) are used for several therapeutic applications to improve the functions of bone, cardiac, nervous tissue as well as to facilitate the repopulation of hematopoietic stem cells. MSC give rise to the non-hematopoietic stromal cells of the bone marrow and are important for the maintenance of normal hematopoiesis. Chemotherapeutic drugs used for treatment of leukemia extensively damage the stromal cells and alter their gene expression profiles. METHODS: We determined the changes in adipogenic, osteogenic differentiation, phenotypic and gene expression in MSC during treatment with chemotherapeutic drugs cytarabine, daunorubicin and vincristine. We also tested anti-cancer effects of drug treated MSC on leukemia cells. RESULTS: Treatment with the chemotherapeutic drugs resulted in functional defects in MSC, leading to reduced proliferation, osteogenic and adipogenic differentiation. The drug treated MSC also showed decreased expression of cell surface receptors, and the changes in proliferation, phenotype and differentiation defect was partially reversible after withdrawing the drugs from the cells. The drug treated MSC showed increased expression of cytokines, IL6, FGF2 and TNFA but reduced levels of differentiation markers SOX9 and ACTC1. Drug treated MSC also contributed to reduced anti-cancer effects in leukemia cells. CONCLUSIONS: Chemotherapeutic drug treatment altered the phenotype, osteogenic and adipogenic differentiation potential of MSC and modified the gene expression profile of the cells to render them more chemoprotective of the leukemic cells. Thus, additional therapeutic efforts to target the stromal cell population will help in preventing chemoresistance, disease relapse in leukemia and to maintain a healthy bone marrow stroma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12929-018-0407-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-01-19 /pmc/articles/PMC5774172/ /pubmed/29351753 http://dx.doi.org/10.1186/s12929-018-0407-7 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Somaiah, Chinnapaka
Kumar, Atul
Sharma, Renu
Sharma, Amit
Anand, Trishna
Bhattacharyya, Jina
Das, Damodar
Deka Talukdar, Sewali
Jaganathan, Bithiah Grace
Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title_full Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title_fullStr Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title_full_unstemmed Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title_short Mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
title_sort mesenchymal stem cells show functional defect and decreased anti-cancer effect after exposure to chemotherapeutic drugs
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774172/
https://www.ncbi.nlm.nih.gov/pubmed/29351753
http://dx.doi.org/10.1186/s12929-018-0407-7
work_keys_str_mv AT somaiahchinnapaka mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT kumaratul mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT sharmarenu mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT sharmaamit mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT anandtrishna mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT bhattacharyyajina mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT dasdamodar mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT dekatalukdarsewali mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs
AT jaganathanbithiahgrace mesenchymalstemcellsshowfunctionaldefectanddecreasedanticancereffectafterexposuretochemotherapeuticdrugs