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08:41
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Bone marrow osteoblast damage by chemotherapeutic agents.
Stephanie L Rellick1, Heather O'Leary, Debbie Piktel
1Cancer Cell Biology Program, School of Medicine, West Virginia University, Morgantown, West Virginia, United States of America.
Plos One
|February 25, 2012
Summary
Chemotherapy damages osteoblasts, crucial bone marrow niche cells. This damage impairs their ability to support stem cell growth and function, potentially causing hematopoietic deficits after transplantation.
Area of Science:
- Hematology
- Stem Cell Biology
- Oncology
Background:
- Hematopoietic reconstitution relies on a supportive bone marrow microenvironment.
- Osteoblasts are a key component of this niche, supporting stem and progenitor cells.
Purpose of the Study:
- To investigate the impact of chemotherapy on osteoblasts and their supportive capacity for hematopoietic cells.
- To determine if chemotherapy-induced osteoblast damage contributes to post-transplantation hematopoietic deficits.
Main Methods:
- Human primary osteoblasts (HOB) were treated with melphalan or VP-16.
- TGF-β1 activity was assessed via phospho-Smad2.
- Co-culture experiments with HOB and hematopoietic stem cells (hESC, CD34+ cells) were performed.
- Gene expression profiles were analyzed.
Main Results:
- Melphalan and VP-16 increased TGF-β1 activity in HOB.
- Chemotherapy-treated HOB showed reduced support for B lineage cell chemotaxis and adherence.
- Co-culture with treated HOB altered the profiles of hESC and CD34+ cells.
- Functional deficits were downstream of gene expression changes.
Conclusions:
- Chemotherapy agents like melphalan and VP-16 damage osteoblasts, compromising the bone marrow niche.
- This osteoblast vulnerability may explain hematopoietic deficits observed after high-dose chemotherapy and transplantation.
- Protecting osteoblasts could be a strategy to improve transplant outcomes.
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