Effects of high-dose chemotherapy on bone marrow multipotent mesenchymal stromal cells isolated from lymphoma patients.
OBJECTIVE
High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation is a widely applied treatment for hematological and autoimmune diseases. Little is known about the effects of this therapy on multipotent mesenchymal stromal cells (MSCs). We aimed to characterize, morphologically and functionally, MSCs isolated from bone marrow aspirates of patients after HDCT.


METHODS
We studied 12 consecutive lymphoma patients submitted to BEAM conditioning regimen followed by autologous stem cell transplantation 28 to 1836 days before the sample collection. Thirteen normal donors were used as control. MSCs were isolated by adherence to plastic and expanded ex vivo by culture in flasks containing alpha-minimum essential medium plus 15% fetal bovine serum.


RESULTS
The cell population isolated showed a typical MSC morphology, immunophenotype, and differentiation capacity into adipogenic, osteogenic, and chondrogenic lineages. The MSCs obtained from patients with Hodgkin's disease and non-Hodgkin's lymphoma showed decreased fibroblastoid colony-forming unit count (p = 0.023) and increased doubling time (p = 0.031) related to the control group. The total cell expansion of MSCs from normal subjects was marginally superior to the patient group (p = 0.064). There were no differences in gene expression profile, MSCs plasticity, or hematopoiesis support capability between control and patient group.


CONCLUSIONS
Results suggest that HDCT applied to lymphoma patients damaged MSCs, which was demonstrated by their reduced clonogenic potential, doubling time, and cell expansion rates when compared to controls.
National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Ribeirão Preto, Brazil; Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
Karen de Lima
Kde L
Prata
Maristela Delgado
MD
Orellana
Gil Cunha
GC
De Santis
Simone
S
Kashima
Aparecida Maria
AM
Fontes
Rita de Cássia Viu
Rde C
Carrara
Patricia Vianna Bonini
PV
Palma
Luciano
L
Neder
Dimas Tadeu
DT
Covas
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001854:Bone Marrow Cells / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D006689:Hodgkin Disease; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000473:pathology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D000970:Antineoplastic Agents