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EFFECTS OF BONE MARROW MESENCHYMAL CELLS FROM IMMUNE THROMBOCYTOPENIA PATIENTS ON THE BIOLOGICAL BEHAVIORS OF MEGAKARYOCYTES
Author(s): ,
Junying Wang
Affiliations:
Department of Hematology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Xin Li
Affiliations:
Department of Hematology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Tingyu Yin
Affiliations:
Department of Hematology,Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Jia Liu
Affiliations:
Department of Hematology,Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Xiaodong Wang
Affiliations:
Department of Rheumatology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Lan Xu
Affiliations:
Department of Hematology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
,
Andi Wang
Affiliations:
Department of Hematology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
Hua Zhong
Affiliations:
Department of Hematology,Ren Ji Hospital, South Campus,School of Medicine, Shanghai Jiao Tong University,Shanghai,China
(Abstract release date: 05/17/18) EHA Library. Zhong H. 06/16/18; 214473; S888
Hua Zhong
Hua Zhong
Contributions
Abstract

Abstract: S888

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 16:30 - 16:45

Location: Room A9

Background
Immune thrombocytopenia(ITP) is an autoimmune disease characterized by increased platelet destruction as well as impaired production. The pathogenesis of impaired platelet production in ITP is still ill-defined. The bone marrow microenvironment plays the critical role in platelet generation. As the important component of the bone marrow microenvironment, bone marrow mesenchymal cells(BMCs) also play a critical role in regulating platelet production. BMCs can sustain MK differentiation and platelet formation through multiple mechanisms, including expressing many of the cytokines that are involved in megakaryocytic developments, as well as providing mechanical supports through adhesion molecules mediated direct contact. A series of studies have demonstrated the defective BMCs from ITP patients. However, whether the effects of BMCs in regulating megakaryopoiesis have changed in ITP is still not clear. In this study we focused on the interaction of BMCs and megakaryocytes, compared many aspects of BMCs from ITP and Normal controls, in order to deepen our understanding of the pathogenesis of ITP.

Aims
To investigate changes in the proliferation, survival and cytokines expression of BMCs derived from ITP patients, as well as to evaluate their influences on the biological behaviors of megakaryocytes.

Methods
Bone marrow samples were obtained from 7 ITP patients and 5 normal controls, and BMCs were cultivated by the whole marrow adherent method. The surface markers of BMCs and the basal cell apoptosis rate were analyzed by flow cytometry. Proliferation of BMCs were assessed by Cell Counting Kit-8 method. HEL cells were induced to undergo megakaryocytic differentiation by using nanomolar concentrations of Phorbol 12-myristate 13-acetate (PMA). The induced HEL cells were grouped and co-cultured with BMCs from different resources, followed by surface protein CD41a detection and apoptosis analysis through FCM. The expression levels of IL6、IL11、TPO、SCF mRNA and protein in BMCs were detected by Real-time Fluorescent quantitative PCR and Enzyme Linked Immunosorbent Assay.

Results
BMCs from ITP patients grew progressively slowly, and cell basal apoptotic rates were higher than that of normal controls. BMCs from normal controls significantly promoted the CD41a expression as well as reduced the apoptosis rate of induced HEL(megakaryocyte-like cells) by co-culture in vitro. Whereas, this ability was much weaker in BMCs from ITP patients; The expression Levels of IL6, SCF mRNA and IL6 protein were significantly decreased in ITP BMCs.

Conclusion
BMCs from ITP patients exhibited impaired proliferation and excessive apoptosis when cultured in virto. BMCs from ITP also show defects in supporting megakaryocytic differentiation and survival under co-culture condition, which may be resulted from their deficiencies in expressing cytokines IL6 and SCF.

Session topic: 34. Bleeding disorders (congenital and acquired)

Keyword(s): Bone microenvironment, Immune thrombocytopenia (ITP), Megakaryocyte differentiation, Mesenchymal cells

Abstract: S888

Type: Oral Presentation

Presentation during EHA23: On Saturday, June 16, 2018 from 16:30 - 16:45

Location: Room A9

Background
Immune thrombocytopenia(ITP) is an autoimmune disease characterized by increased platelet destruction as well as impaired production. The pathogenesis of impaired platelet production in ITP is still ill-defined. The bone marrow microenvironment plays the critical role in platelet generation. As the important component of the bone marrow microenvironment, bone marrow mesenchymal cells(BMCs) also play a critical role in regulating platelet production. BMCs can sustain MK differentiation and platelet formation through multiple mechanisms, including expressing many of the cytokines that are involved in megakaryocytic developments, as well as providing mechanical supports through adhesion molecules mediated direct contact. A series of studies have demonstrated the defective BMCs from ITP patients. However, whether the effects of BMCs in regulating megakaryopoiesis have changed in ITP is still not clear. In this study we focused on the interaction of BMCs and megakaryocytes, compared many aspects of BMCs from ITP and Normal controls, in order to deepen our understanding of the pathogenesis of ITP.

Aims
To investigate changes in the proliferation, survival and cytokines expression of BMCs derived from ITP patients, as well as to evaluate their influences on the biological behaviors of megakaryocytes.

Methods
Bone marrow samples were obtained from 7 ITP patients and 5 normal controls, and BMCs were cultivated by the whole marrow adherent method. The surface markers of BMCs and the basal cell apoptosis rate were analyzed by flow cytometry. Proliferation of BMCs were assessed by Cell Counting Kit-8 method. HEL cells were induced to undergo megakaryocytic differentiation by using nanomolar concentrations of Phorbol 12-myristate 13-acetate (PMA). The induced HEL cells were grouped and co-cultured with BMCs from different resources, followed by surface protein CD41a detection and apoptosis analysis through FCM. The expression levels of IL6、IL11、TPO、SCF mRNA and protein in BMCs were detected by Real-time Fluorescent quantitative PCR and Enzyme Linked Immunosorbent Assay.

Results
BMCs from ITP patients grew progressively slowly, and cell basal apoptotic rates were higher than that of normal controls. BMCs from normal controls significantly promoted the CD41a expression as well as reduced the apoptosis rate of induced HEL(megakaryocyte-like cells) by co-culture in vitro. Whereas, this ability was much weaker in BMCs from ITP patients; The expression Levels of IL6, SCF mRNA and IL6 protein were significantly decreased in ITP BMCs.

Conclusion
BMCs from ITP patients exhibited impaired proliferation and excessive apoptosis when cultured in virto. BMCs from ITP also show defects in supporting megakaryocytic differentiation and survival under co-culture condition, which may be resulted from their deficiencies in expressing cytokines IL6 and SCF.

Session topic: 34. Bleeding disorders (congenital and acquired)

Keyword(s): Bone microenvironment, Immune thrombocytopenia (ITP), Megakaryocyte differentiation, Mesenchymal cells

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