Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology

Aplastic anemia (AA) is a heterogeneous disorder of bone marrow failure syndrome. Suggested mechanisms include a primary stem cell deficiency or defect, a secondary stem cell defect due to abnormal regulation between cell death and differentiation, or a deficient microenvironment. In this study, we...

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Main Authors: Sumanta Chatterjee, Ranjan Kumar Dutta, Pratima Basak, Prosun Das, Madhurima Das, Jacintha Archana Pereira, Malay Chaklader, Samaresh Chaudhuri, Sujata Law
Format: Article
Language:English
Published: Wiley 2010-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.4061/2010/932354
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author Sumanta Chatterjee
Ranjan Kumar Dutta
Pratima Basak
Prosun Das
Madhurima Das
Jacintha Archana Pereira
Malay Chaklader
Samaresh Chaudhuri
Sujata Law
author_facet Sumanta Chatterjee
Ranjan Kumar Dutta
Pratima Basak
Prosun Das
Madhurima Das
Jacintha Archana Pereira
Malay Chaklader
Samaresh Chaudhuri
Sujata Law
author_sort Sumanta Chatterjee
collection DOAJ
description Aplastic anemia (AA) is a heterogeneous disorder of bone marrow failure syndrome. Suggested mechanisms include a primary stem cell deficiency or defect, a secondary stem cell defect due to abnormal regulation between cell death and differentiation, or a deficient microenvironment. In this study, we have tried to investigate the alterations in hematopoietic microenvironment and underlying mechanisms involved in such alterations in an animal model of drug induced AA. We presented the results of studying long term marrow culture, marrow ultra-structure, marrow adherent and hematopoietic progenitor cell colony formation, flowcytometric analysis of marrow stem and stromal progenitor populations and apoptosis mechanism involved in aplastic anemia. The AA marrow showed impairment in cellular proliferation and maturation and failed to generate a functional stromal microenvironment even after 19 days of culture. Ultra-structural analysis showed a degenerated and deformed marrow cellular association in AA. Colony forming units (CFUs) were also severely reduced in AA. Significantly decreased marrow stem and stromal progenitor population with subsequently increased expression levels of both the extracellular and intracellular apoptosis inducer markers in the AA marrow cells essentially pointed towards the defective hematopoiesis; moreover, a deficient and apoptotic microenvironment and the microenvironmental components might have played the important role in the possible pathogenesis of AA.
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spelling doaj-art-ed41c9c6cada4358ac8cf32fc11ec39e2025-08-20T02:22:09ZengWileyStem Cells International1687-96782010-01-01201010.4061/2010/932354932354Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease PathologySumanta Chatterjee0Ranjan Kumar Dutta1Pratima Basak2Prosun Das3Madhurima Das4Jacintha Archana Pereira5Malay Chaklader6Samaresh Chaudhuri7Sujata Law8Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaStem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Calcutta 700073, IndiaAplastic anemia (AA) is a heterogeneous disorder of bone marrow failure syndrome. Suggested mechanisms include a primary stem cell deficiency or defect, a secondary stem cell defect due to abnormal regulation between cell death and differentiation, or a deficient microenvironment. In this study, we have tried to investigate the alterations in hematopoietic microenvironment and underlying mechanisms involved in such alterations in an animal model of drug induced AA. We presented the results of studying long term marrow culture, marrow ultra-structure, marrow adherent and hematopoietic progenitor cell colony formation, flowcytometric analysis of marrow stem and stromal progenitor populations and apoptosis mechanism involved in aplastic anemia. The AA marrow showed impairment in cellular proliferation and maturation and failed to generate a functional stromal microenvironment even after 19 days of culture. Ultra-structural analysis showed a degenerated and deformed marrow cellular association in AA. Colony forming units (CFUs) were also severely reduced in AA. Significantly decreased marrow stem and stromal progenitor population with subsequently increased expression levels of both the extracellular and intracellular apoptosis inducer markers in the AA marrow cells essentially pointed towards the defective hematopoiesis; moreover, a deficient and apoptotic microenvironment and the microenvironmental components might have played the important role in the possible pathogenesis of AA.http://dx.doi.org/10.4061/2010/932354
spellingShingle Sumanta Chatterjee
Ranjan Kumar Dutta
Pratima Basak
Prosun Das
Madhurima Das
Jacintha Archana Pereira
Malay Chaklader
Samaresh Chaudhuri
Sujata Law
Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
Stem Cells International
title Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
title_full Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
title_fullStr Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
title_full_unstemmed Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
title_short Alteration in Marrow Stromal Microenvironment and Apoptosis Mechanisms Involved in Aplastic Anemia: An Animal Model to Study the Possible Disease Pathology
title_sort alteration in marrow stromal microenvironment and apoptosis mechanisms involved in aplastic anemia an animal model to study the possible disease pathology
url http://dx.doi.org/10.4061/2010/932354
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