Effects of high-dose chemotherapy on bone marrow multipotent mesenchymal stromal cells isolated from lymphoma patients
Received 17 September 2009; received in revised form 26 January 2010; accepted 29 January 2010. published online 08 February 2010.
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.
Materials and 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 α−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.
aNational Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Ribeirão Preto, Brazil
bFaculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil
Offprint requests to: Dimas Tadeu Covas, M.D., Ph.D., Centro Regional de Hemoterapia, FMRP, USP, Rua Tenente Catão Roxo, 2501, 14051-140 Ribeirão Preto, SP, Brazil
ABSTRACT