Author ORCID Identifier
https://orcid.org/0000-0002-5162-2761
https://orcid.org/0000-0003-1321-1520
https://orcid.org/0000-0001-6706-5923
https://orcid.org/0000-0002-5573-9174
N/A
https://orcid.org/0000-0002-3810-9656
https://orcid.org/0000-0001-8916-4092
https://orcid.org/0000-0001-8836-6653
N/A
https://orcid.org/0000-0002-2175-4472
https://orcid.org/0000-0002-6715-1415
https://orcid.org/0000-0002-6747-680X
Document Type
Article
Publication Date
2012
College/Unit
School of Medicine
Department/Program/Center
Medicine
Abstract
Hematopoietic reconstitution, following bone marrow or stem cell transplantation, requires a microenvironment niche capable of supporting both immature progenitors and stem cells with the capacity to differentiate and expand. Osteoblasts comprise one important component of this niche. We determined that treatment of human primary osteoblasts (HOB) with melphalan or VP-16 resulted in increased phospho-Smad2, consistent with increased TGF-β1 activity. This increase was coincident with reduced HOB capacity to support immature B lineage cell chemotaxis and adherence. The supportive deficit was not limited to committed progenitor cells, as human embryonic stem cells (hESC) or human CD34+ bone marrow cells co-cultured with HOB pre-exposed to melphalan, VP-16 or rTGF-β1 had profiles distinct from the same populations co-cultured with untreated HOB. Functional support deficits were downstream of changes in HOB gene expression profiles following chemotherapy exposure. Melphalan and VP-16 induced damage of HOB suggests vulnerability of this critical niche to therapeutic agents frequently utilized in pre-transplant regimens and suggests that dose escalated chemotherapy may contribute to post-transplantation hematopoietic deficits by damaging structural components of this supportive niche.
Digital Commons Citation
Rellick, Stephanie L.; O'Leary, Heather; Piktel, Debbie; Walton, Cheryl; Fortney, James E.; Akers, Stephen M.; Martin, Karen H.; Denvir, James; Boskovic, Goran; Primerano, Donald A.; Vos, Jeffrey; Bailey, Nathanael; Gencheva, Marieta; and Gibson, Laura F., "Bone Marrow Osteoblast Damage by Chemotherapeutic Agents" (2012). Faculty & Staff Scholarship. 2722.
https://researchrepository.wvu.edu/faculty_publications/2722
Source Citation
Rellick SL, O'Leary H, Piktel D, Walton C, Fortney JE, Akers SM, et al. (2012) Bone Marrow Osteoblast Damage by Chemotherapeutic Agents. PLoS ONE 7(2): e30758. https://doi.org/10.1371/journal.pone.0030758
Comments
© 2012 Rellick et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.