BONE MARROW STROMAL CELLS FUNCTIONAL CHARACTERISTICS STUDY IN RECIPIENTS BEFORE ALLO-BMT.
(Abstract release date: 05/19/16)
EHA Library. Barkhatov I. 06/09/16; 132683; E1134
Dr. Ildar Barkhatov
Contributions
Contributions
Abstract
Abstract: E1134
Type: Eposter Presentation
Background
The role of the stromal microenvironment in hematopoietic stem cell transplantation (HSCT) is based on nonlineage-specific effects on proliferation and differentiation of HSCs. Deficient graft functioning observed in some cases necessitates development of functional tests for the stromal cells, in order to provide clinical indications for co-transplanting of hematopoietic and bone marrow stromal cells (BMSC), and evaluable introduction of alternative therapeutic approaches.
Aims
The aim of this study was to investigate the role of bone marrow stromal cells in the course of donor marrow cells engraftment and their significance in post-transplant complications.
Methods
The study included clinical observation of the post-transplant course in ten patients with acute myeloid leukemia (AML) and 7 healthy donors. Bone marrow nucleated cells were selectively harvested two weeks prior to BMT, followed by monolayer culture in alpha-MEM culture medium with 20% fetal bovine serum. Upon growth of fibroblast-like cell colonies (CFU-F), their hematopoiesis-supporting activity was determined in the agar-drop/liquid culture system, as well as their differentiating ability along adipogenic and osteogenic pathways. We have also analyzed the relative expression of selectin and CXCR4 genes in these cells.
Results
When comparing functional characteristics of BMSC from healthy donors and AML patients, an increased hemostimulatory activity of the latter was noted, as reflected by an increase in large and small CFU-GM numbers (p <0.02). In addition, an increase in differentiation along adipogenic and osteogenic pathways was observed in AML patients (p = 0.03). Moreover, the number of CFU-Fs, capable for adipogenic differentiation was inversely correlated with platelet recovery time (p = 0.05). In contrast, higher numbers of osteogenic colonies in culture were associated with an increased time to leukocyte lineage recovery (p = 0.05). When analyzing gene expression in BMSC population, a decreased expression of the CXCR4 gene responsible for the homing effect, with age of the patient's (p = 0.05) was noted. The selectin gene expression in BMSC was higher by AML patients as compared to healthy donors.
Conclusion
Stromal cells derived from the patients’ bone marrow exhibit higher proliferative activity and marked expression of molecules mediating HSC homing, as compared with a group of healthy donors. That finding could be explained by affection of stromal cells by previous chemotherapy and myelosuppression. BMSC from AML patients taken before bone marrow transplantation are characterized by a more pronounced capacity to osteogenic and adipogenic differentiation than those from healthy donors. Increased adipogenic differentiation ability of the BMSCs is associated with a more rapid recovery of hematopoiesis.
Session topic: E-poster
Keyword(s): Bone marrow stroma, Bone marrow transplant, Engraftment, Stromal cell
Type: Eposter Presentation
Background
The role of the stromal microenvironment in hematopoietic stem cell transplantation (HSCT) is based on nonlineage-specific effects on proliferation and differentiation of HSCs. Deficient graft functioning observed in some cases necessitates development of functional tests for the stromal cells, in order to provide clinical indications for co-transplanting of hematopoietic and bone marrow stromal cells (BMSC), and evaluable introduction of alternative therapeutic approaches.
Aims
The aim of this study was to investigate the role of bone marrow stromal cells in the course of donor marrow cells engraftment and their significance in post-transplant complications.
Methods
The study included clinical observation of the post-transplant course in ten patients with acute myeloid leukemia (AML) and 7 healthy donors. Bone marrow nucleated cells were selectively harvested two weeks prior to BMT, followed by monolayer culture in alpha-MEM culture medium with 20% fetal bovine serum. Upon growth of fibroblast-like cell colonies (CFU-F), their hematopoiesis-supporting activity was determined in the agar-drop/liquid culture system, as well as their differentiating ability along adipogenic and osteogenic pathways. We have also analyzed the relative expression of selectin and CXCR4 genes in these cells.
Results
When comparing functional characteristics of BMSC from healthy donors and AML patients, an increased hemostimulatory activity of the latter was noted, as reflected by an increase in large and small CFU-GM numbers (p <0.02). In addition, an increase in differentiation along adipogenic and osteogenic pathways was observed in AML patients (p = 0.03). Moreover, the number of CFU-Fs, capable for adipogenic differentiation was inversely correlated with platelet recovery time (p = 0.05). In contrast, higher numbers of osteogenic colonies in culture were associated with an increased time to leukocyte lineage recovery (p = 0.05). When analyzing gene expression in BMSC population, a decreased expression of the CXCR4 gene responsible for the homing effect, with age of the patient's (p = 0.05) was noted. The selectin gene expression in BMSC was higher by AML patients as compared to healthy donors.
Conclusion
Stromal cells derived from the patients’ bone marrow exhibit higher proliferative activity and marked expression of molecules mediating HSC homing, as compared with a group of healthy donors. That finding could be explained by affection of stromal cells by previous chemotherapy and myelosuppression. BMSC from AML patients taken before bone marrow transplantation are characterized by a more pronounced capacity to osteogenic and adipogenic differentiation than those from healthy donors. Increased adipogenic differentiation ability of the BMSCs is associated with a more rapid recovery of hematopoiesis.
Session topic: E-poster
Keyword(s): Bone marrow stroma, Bone marrow transplant, Engraftment, Stromal cell
Abstract: E1134
Type: Eposter Presentation
Background
The role of the stromal microenvironment in hematopoietic stem cell transplantation (HSCT) is based on nonlineage-specific effects on proliferation and differentiation of HSCs. Deficient graft functioning observed in some cases necessitates development of functional tests for the stromal cells, in order to provide clinical indications for co-transplanting of hematopoietic and bone marrow stromal cells (BMSC), and evaluable introduction of alternative therapeutic approaches.
Aims
The aim of this study was to investigate the role of bone marrow stromal cells in the course of donor marrow cells engraftment and their significance in post-transplant complications.
Methods
The study included clinical observation of the post-transplant course in ten patients with acute myeloid leukemia (AML) and 7 healthy donors. Bone marrow nucleated cells were selectively harvested two weeks prior to BMT, followed by monolayer culture in alpha-MEM culture medium with 20% fetal bovine serum. Upon growth of fibroblast-like cell colonies (CFU-F), their hematopoiesis-supporting activity was determined in the agar-drop/liquid culture system, as well as their differentiating ability along adipogenic and osteogenic pathways. We have also analyzed the relative expression of selectin and CXCR4 genes in these cells.
Results
When comparing functional characteristics of BMSC from healthy donors and AML patients, an increased hemostimulatory activity of the latter was noted, as reflected by an increase in large and small CFU-GM numbers (p <0.02). In addition, an increase in differentiation along adipogenic and osteogenic pathways was observed in AML patients (p = 0.03). Moreover, the number of CFU-Fs, capable for adipogenic differentiation was inversely correlated with platelet recovery time (p = 0.05). In contrast, higher numbers of osteogenic colonies in culture were associated with an increased time to leukocyte lineage recovery (p = 0.05). When analyzing gene expression in BMSC population, a decreased expression of the CXCR4 gene responsible for the homing effect, with age of the patient's (p = 0.05) was noted. The selectin gene expression in BMSC was higher by AML patients as compared to healthy donors.
Conclusion
Stromal cells derived from the patients’ bone marrow exhibit higher proliferative activity and marked expression of molecules mediating HSC homing, as compared with a group of healthy donors. That finding could be explained by affection of stromal cells by previous chemotherapy and myelosuppression. BMSC from AML patients taken before bone marrow transplantation are characterized by a more pronounced capacity to osteogenic and adipogenic differentiation than those from healthy donors. Increased adipogenic differentiation ability of the BMSCs is associated with a more rapid recovery of hematopoiesis.
Session topic: E-poster
Keyword(s): Bone marrow stroma, Bone marrow transplant, Engraftment, Stromal cell
Type: Eposter Presentation
Background
The role of the stromal microenvironment in hematopoietic stem cell transplantation (HSCT) is based on nonlineage-specific effects on proliferation and differentiation of HSCs. Deficient graft functioning observed in some cases necessitates development of functional tests for the stromal cells, in order to provide clinical indications for co-transplanting of hematopoietic and bone marrow stromal cells (BMSC), and evaluable introduction of alternative therapeutic approaches.
Aims
The aim of this study was to investigate the role of bone marrow stromal cells in the course of donor marrow cells engraftment and their significance in post-transplant complications.
Methods
The study included clinical observation of the post-transplant course in ten patients with acute myeloid leukemia (AML) and 7 healthy donors. Bone marrow nucleated cells were selectively harvested two weeks prior to BMT, followed by monolayer culture in alpha-MEM culture medium with 20% fetal bovine serum. Upon growth of fibroblast-like cell colonies (CFU-F), their hematopoiesis-supporting activity was determined in the agar-drop/liquid culture system, as well as their differentiating ability along adipogenic and osteogenic pathways. We have also analyzed the relative expression of selectin and CXCR4 genes in these cells.
Results
When comparing functional characteristics of BMSC from healthy donors and AML patients, an increased hemostimulatory activity of the latter was noted, as reflected by an increase in large and small CFU-GM numbers (p <0.02). In addition, an increase in differentiation along adipogenic and osteogenic pathways was observed in AML patients (p = 0.03). Moreover, the number of CFU-Fs, capable for adipogenic differentiation was inversely correlated with platelet recovery time (p = 0.05). In contrast, higher numbers of osteogenic colonies in culture were associated with an increased time to leukocyte lineage recovery (p = 0.05). When analyzing gene expression in BMSC population, a decreased expression of the CXCR4 gene responsible for the homing effect, with age of the patient's (p = 0.05) was noted. The selectin gene expression in BMSC was higher by AML patients as compared to healthy donors.
Conclusion
Stromal cells derived from the patients’ bone marrow exhibit higher proliferative activity and marked expression of molecules mediating HSC homing, as compared with a group of healthy donors. That finding could be explained by affection of stromal cells by previous chemotherapy and myelosuppression. BMSC from AML patients taken before bone marrow transplantation are characterized by a more pronounced capacity to osteogenic and adipogenic differentiation than those from healthy donors. Increased adipogenic differentiation ability of the BMSCs is associated with a more rapid recovery of hematopoiesis.
Session topic: E-poster
Keyword(s): Bone marrow stroma, Bone marrow transplant, Engraftment, Stromal cell
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