Disruption of bone marrow stromal cell function by etoposide.
Long-term deficits in hematopoietic reconstitution following aggressive chemotherapeutic regimens used before transplantation may be a result, in part, of damage to the bone marrow microenvironment. Disruption of the hematopoietic microenvironment is indicated by delays in functional recovery of the immune system in spite of delivery of healthy peripheral blood or bone marrow progenitor cells. Cultures of primary human bone marrow stromal cells and a cloned murine stromal cell line, S10, were evaluated for functional changes following in vitro exposure to the chemotherapeutic agent, etoposide (VP-16). Stromal cells had reduced capacity to support lymphoid or myeloid cell proliferation following chemotherapy treatment. A consistent reduction of vascular cell adhesion molecule-1 (VCAM-1) on bone marrow stromal cells also followed VP-16 exposure. These observations indicate that functional disruption of the bone marrow microenvironment by chemotherapeutic regimens must be considered when attempting to optimize patient recovery from hematopoietic transplantation.
Gibson
L F
LF
Department of Pediatrics, West Virginia University Health Sciences Center, Morgantown 26506, USA.
Fortney
J
J
Landreth
K S
KS
Piktel
D
D
Ericson
S G
SG
Lynch
J P
JP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology*; D005353:Fibronectins / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D017154:Stromal Cells / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D005353:Fibronectins; D019010:Vascular Cell Adhesion Molecule-1; D005047:Etoposide