Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy.
Hematopoietic recovery after high-dose chemotherapy (HDC) in the treatment of hematological diseases may be slow and/or incomplete. This is generally attributed to progressive hematopoietic stem cell failure, although defective hematopoiesis may be in part due to poor stromal function. Chemotherapy is known to damage mature bone marrow stromal cells in vitro, but the extent to which marrow mesenchymal stem cells (MSCs) are damaged by HDC in vivo is largely unknown. To address this question, the phenotype and functional properties of marrow MSCs derived from untreated and chemotherapeutically treated patients with hematological malignancy were compared. This study demonstrates a significant reduction in MSC expansion and MSC CD44 expression by MSCs derived from patients receiving HDC regimens, thus implicating potential disadvantages in the use of autologous MSCs in chemotherapeutically pretreated patients for future therapeutic strategies. The clinical importance of these HDC-induced defects we have observed could be determined through prospective randomized trials of the effects of MSC cotransplantation on hematopoietic recovery in the setting of HDC with and without hematopoietic stem cell rescue.
Kemp
Kevin
K
Center for Research in Biomedicine, Faculty of Applied Sciences, University of West of England, Bristol, UK. kevin.kemp@bristol.ac.uk
Morse
Ruth
R
Wexler
Sarah
S
Cox
Christine
C
Mallam
Elizabeth
E
Hows
Jill
J
Donaldson
Craig
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D008297:Male; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D017154:Stromal Cells
D018960:Hyaluronan Receptors