scholarly journals Dysfunctional Bone Marrow Mesenchymal Stem Cells in Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation

2018 ◽  
Vol 24 (10) ◽  
pp. 1981-1989 ◽  
Author(s):  
Yang Song ◽  
Hong-Yan Zhao ◽  
Zhong-Shi Lyu ◽  
Xie-Na Cao ◽  
Min-Min Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Marrow Mesenchymal Stem Cells ◽  
Poor Graft Function

scholarly journals Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

2020 ◽  
Vol 11 ◽  
pp. 204062072094874
Author(s):  
Juan Chen ◽  
Hongtao Wang ◽  
Jiaxi Zhou ◽  
Sizhou Feng
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Poor Graft Function

Poor graft function (PGF) following allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a life-threatening complication and is characterized by bilineage or trilineage blood cell deficiency and hypoplastic marrow with full chimerism. With the rapid development of allo-HSCT, especially haploidentical-HSCT, PGF has become a growing concern. The most common risk factors illustrated by recent studies include low dose of infused CD34+ cells, donor-specific antibody, cytomegalovirus infection, graft versus host disease (GVHD), iron overload and splenomegaly, among others. Because of the poor prognosis of PGF, it is crucial to uncover the underlying mechanism, which remains elusive. Recent studies have suggested that the bone marrow microenvironment may play an important role in the pathogenesis of PGF. Deficiency and dysfunction of endothelial cells and mesenchymal stem cells, elevated reactive oxygen species (ROS) levels, and immune abnormalities are believed to contribute to PGF. In this review, we also discuss recent clinical trials that evaluate the safety and efficacy of new strategies in patients with PGF. CD34+-selected stem-cell boost (SCB) is effective with an acceptable incidence of GVHD, despite the need for a second donation. Alternative strategies including the applications of mesenchymal stem cells, N-acetyl-l-cysteine (NAC), and eltrombopag have shown favorable outcomes, but further large-scale studies are needed due to the small sample sizes of the recent clinical trials.

scholarly journals CircRNA_014511 affects the radiosensitivity of bone marrow mesenchymal stem cells by binding to miR-29b-2-5p

2019 ◽  
Author(s):  
Yanjie Wang ◽  
Junhua Zhang ◽  
Jian Li ◽  
Rong Gui ◽  
Xinmin Nie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Marrow Mesenchymal Stem Cells ◽  
Total Body

Hematopoietic stem cell transplantation is commonly used in patients with certain hematological or bone marrow tumors. Total body irradiation combined with chemotherapy is part of the preconditioning protocol that was the most commonly used before hematopoietic stem cell transplantation. However, total body irradiation preconditioning damages other normal cells in bone marrow. Therefore, exploring the mechanism of radiation resistance in bone marrow mesenchymal stem cells is of great significance for recovering the hematopoietic function after cell transplantation. This study aimed to demonstrate the miR-29b adsorption of circRNA_014511 and explore the effect of circRNA_014511 on radiosensitivity of bone marrow mesenchymal stem cells. In this study, circRNA_014511 overexpression vector was constructed and transfected into bone marrow mesenchymal stem cells, miR-29b-2-5p and P53 were found to be decreased, which could be reversed by miR29b-mimics. Dual luciferase reporter assay confirmed the binding of circRNA_014511 and mmu-miR-29b-2-5p. Flow cytometry analysis showed the apoptosis rate of bone marrow mesenchymal stem cells overexpressing circRNA_014511 was significantly decreased. In the circRNA_014511 transfection group, after cells were subjected to 6Gy irradiation, G2 phase arrest appeared, the expression of P21 and GADD45A was significantly decreased, and cyclin B1 was significantly increased. Colony formation assay showed the survival fraction of circRNA_014511 overexpression cells after irradiation was significantly higher than control group, and the radiosensitivity was decreased. In conclusion，our findings demonstrated that circRNA_014511 could inhibit the expression of P53 by binding miR-29b-2-5p, and decrease the radiosensitivity of bone marrow mesenchymal stem cells by affecting cell cycle and cell apoptosis.

scholarly journals Impaired Hematopoiesis after Allogeneic Hematopoietic Stem Cell Transplantation: Its Pathogenesis and Potential Treatments

Hemato ◽  
2021 ◽  
Vol 2 (1) ◽  
pp. 43-63
Author(s):  
Masahiro Imamura
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Hematopoietic Stem Cells ◽  
Graft Failure ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Poor Graft Function ◽  
Bone Marrow Niches

Impaired hematopoiesis is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Bone marrow aplasia and peripheral cytopenias arise from primary and secondary graft failure or primary and secondary poor graft function. Chimerism analysis is useful to discriminate these conditions. By determining the pathogenesis of impaired hematopoiesis, a timely and appropriate treatment can be performed. Hematopoietic system principally consists of hematopoietic stem cells and bone marrow microenvironment termed niches. Abnormality in hematopoietic stem and progenitor cells and/or abnormality in the relevant niches give rise to hematological diseases. Allo-HSCT is intended to cure each hematological disease, replacing abnormal hematopoietic stem cells and bone marrow niches with hematopoietic stem cells and bone marrow niches derived from normal donors. Therefore, treatment for graft failure and poor graft function after allo-HSCT is required to proceed based on determining the pathogenesis of impaired hematopoiesis. Recent progress in this area suggests promising treatment manipulations for graft failure and poor graft function.

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