7 research outputs found
Mesenchymal Stromal Cell Irradiation Interferes with the Adipogenic/Osteogenic Differentiation Balance and Improves Their Hematopoietic-Supporting Ability
[EN]Bone marrow mesenchymal stromal cells (MSCs) are precursors of adipocytes and osteoblasts and key regulators
of hematopoiesis. Irradiation is widely used in conditioning regimens. Although MSCs are radioresistant,
the effects of low-dose irradiation on their behavior have not been extensively explored. Our aim
was to evaluate the effect of 2.5 Gy on MSCs. Cells from 25 healthy donors were either irradiated or not (the
latter were used as controls). Cells were characterized following International Society for Cellular Therapy criteria,
including in vitro differentiation assays. Apoptosis was evaluated by annexin V/7-amino-actinomycin
staining. Gene expression profiling and reverse transcriptase (RT)-PCR of relevant genes was also performed.
Finally, long-term bone marrow cultures were performed to test the hematopoietic-supporting ability. Our
results showed that immunophenotypic characterization and viability of irradiated cells was comparable with
that of control cells. Gene expression profiling showed 50 genes differentially expressed. By RT-PCR, SDF-1
and ANGPT were overexpressed, whereas COL1A1 was downregulated in irradiated cells (P = .015, P = .007,
and P = .031, respectively). Interestingly, differentiation of irradiated cells was skewed toward osteogenesis,
whereas adipogenesis was impaired. Higher expression of genes involved in osteogenesis as SPP1 (P = .039)
and lower of genes involved in adipogenesis, CEBPA and PPARG (P = .003 and P = .019), together with an increase
in the mineralization capacity (Alizarin Red) was observed in irradiated cells. After differentiation, adipocyte
counts were decreased in irradiated cells at days 7, 14, and 21 (P = .018 P = .046, and P = .018, respectively).
Also, colony-forming unit granulocyte macrophage number in long-term bone marrow cultures was signifi-
cantly higher in irradiated cells after 4 and 5 weeks (P = .046 and P = .007). In summary, the irradiation of MSCs
with 2.5 Gy improves their hematopoietic-supporting ability by increasing osteogenic differentiation and decreasing
adipogenesis
Osteopaenia and osteoporosis among localized prostate cancer patients treated with long-term androgen deprivation and radiotherapy
Mesenchymal Stromal Cell Irradiation Interferes with the Adipogenic/Osteogenic Differentiation Balance and Improves Their Hematopoietic-Supporting Ability.
Bone marrow mesenchymal stromal cells (MSCs) are precursors of adipocytes and osteoblasts and key regulators of hematopoiesis. Irradiation is widely used in conditioning regimens. Although MSCs are radio-resistant, the effects of low-dose irradiation on their behavior have not been extensively explored. Our aim was to evaluate the effect of 2.5 Gy on MSCs. Cells from 25 healthy donors were either irradiated or not (the latter were used as controls). Cells were characterized following International Society for Cellular Therapy criteria, including in vitro differentiation assays. Apoptosis was evaluated by annexin V/7-amino-actinomycin staining. Gene expression profiling and reverse transcriptase (RT)-PCR of relevant genes was also performed. Finally, long-term bone marrow cultures were performed to test the hematopoietic-supporting ability. Our results showed that immunophenotypic characterization and viability of irradiated cells was comparable with that of control cells. Gene expression profiling showed 50 genes differentially expressed. By RT-PCR, SDF-1 and ANGPT were overexpressed, whereas COL1A1 was downregulated in irradiated cells (P = .015, P = .007, and P = .031, respectively). Interestingly, differentiation of irradiated cells was skewed toward osteogenesis, whereas adipogenesis was impaired. Higher expression of genes involved in osteogenesis as SPP1 (P = .039) and lower of genes involved in adipogenesis, CEBPA and PPARG (P = .003 and P = .019), together with an increase in the mineralization capacity (Alizarin Red) was observed in irradiated cells. After differentiation, adipocyte counts were decreased in irradiated cells at days 7, 14, and 21 (P = .018 P = .046, and P = .018, respectively). Also, colony-forming unit granulocyte macrophage number in long-term bone marrow cultures was significantly higher in irradiated cells after 4 and 5 weeks (P = .046 and P = .007). In summary, the irradiation of MSCs with 2.5 Gy improves their hematopoietic-supporting ability by increasing osteogenic differentiation and decreasing adipogenesis