No abstract available.
Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Metabolism*

Although widely applied in treating hematopoietic malignancies, transplantation of hematopoietic stem/progenitor cells (HSPCs) is impeded by HSPC shortage. Whether circulating HSPCs (cHSPCs) in steady-state blood could be used as an alternative source remains largely elusive. Here we develop a three-dimensional culture system (3DCS) including arginine, glycine, aspartate, and a series of factors. Fourteen-day culture of peripheral blood mononuclear cells (PBMNCs) in 3DCS led to 125- and 70-fold increase of the frequency and number of CD34⁺ cells. Further, 3DCS-expanded cHSPCs exhibited the similar reconstitution rate compared to CD34⁺ HSPCs in bone marrow. Mechanistically, 3DCS fabricated an immunomodulatory niche, secreting cytokines as TNF to support cHSPC survival and proliferation. Finally, 3DCS could also promote the expansion of cHSPCs in patients who failed in HSPC mobilization. Our 3DCS successfully expands rare cHSPCs, providing an alternative source for the HSPC therapy, particularly for the patients/donors who have failed in HSPC mobilization.
Antigens, CD34/metabolism* ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Leukocytes, Mononuclear/metabolism* ; Peptides/metabolism*

The homing and engraftment of hematopoietic stem cells (HSC) into bone marrow is the first critical step for successful clinical hematopoietic stem cell transplantation (HSCT). SDF-1 / CXCR4 is considered to be a very promising target to promote HSC homing. In recent years, with the in-depth research on the HSC homing, a variety of new strategies for promoting HSC homing and engraftment have been explored, such as nuclear hormone receptor, histone deacetylase inhibitor, prostaglandin and metabolic regulation, so as to increase the success rate of HSCT and improve the survival of patients. In this review, the recent research advances in the mechanism of HSC homing and strategies to promote HSC homing and engraftment were summarized and discussed.
Humans ; Hematopoietic Stem Cells/physiology* ; Bone Marrow ; Hematopoietic Stem Cell Transplantation ; Gene Expression Regulation ; Prostaglandins/metabolism*

Cre-lox recombination system consists of two elements: Cre recombinase enzyme and lox sites. Cre recombinase can recombine the lox site sequences by specifically detecting and cutting them. The direction and position of lox sites determine the functional effects of Cre enzyme such as deletion, inversion or chromosomal translocation. The hematopoietic system of mouse consists of multi-lineages and various developmental stage hematopoietic cells that are differentiated from hematopoietic stem cells (hematopoietic stem cells, HSC). The hematopoietic stem cells are maintained in the bone marrow microenvironment (niche). Currently, a variety of floxed conditional-knockout mice, recognized by Cre-lox recombination system, are used for the study of the hematopoietic system. This review summarizes the commonly used Cre transgenic mice and their applications in the study of hematopoietic system.
Animals ; Hematopoietic Stem Cells ; cytology ; metabolism ; Integrases ; Mice ; Mice, Transgenic

Bone marrow macrophage is an important component of bone marrow microenvironment, which is closely related to hematopoietic regulation and hematopoietic stem cell transplantation(HSCT). Recent studies have shown that bone marrow macrophage is an important part of hematopoietic stem cell niche, which can help regulate the mobilization and function of hematopoietic stem/progenitor cells. After HSCT, the microenvironment of bone marrow is damaged and a large number of macrophages infiltrate into the bone marrow. Regulating the macrophage-related signal pathways can promote the recovery of hematopoiesis and the reconstruction of hematopoietic function. Co-culture of macrophages and hematopoietic stem cells (HSC) in vitro significantly increased the number of HSCs and their ability of clone formation, which suggests that macrophages play an important role in the regulation of hematopoiesis in the hematopoietic microenvironment of bone marrow. This paper reviews the recent research progress on the role of macrophages in bone marrow hematopoietic microenvironment.
Humans ; Bone Marrow/metabolism* ; Hematopoietic Stem Cells/physiology* ; Hematopoiesis/physiology* ; Stem Cell Niche ; Macrophages/metabolism*

As the theory of stem cell plasticity was first proposed, we have explored an alternative hypothesis for this phenomenon: namely that adult bone marrow (BM) and umbilical cord blood (UCB) contain more developmentally primitive cells than hematopoietic stem cells (HSCs). In support of this notion, using multiparameter sorting we were able to isolate small Sca1+Lin-CD45- cells and CD133+Lin-CD45- cells from murine BM and human UCB, respectively, which were further enriched for the detection of various early developmental markers such as the SSEA antigen on the surface and the Oct4 and Nanog transcription factors in the nucleus. Similar populations of cells have been found in various organs by our team and others, including the heart, brain and gonads. Owing to their primitive cellular features, such as the high nuclear/cytoplasm ratio and the presence of euchromatin, they are called very small embryonic-like stem cells (VSELs). In the appropriate in vivo models, VSELs differentiate into long-term repopulating HSCs, mesenchymal stem cells (MSCs), lung epithelial cells, cardiomyocytes and gametes. In this review, we discuss the most recent data from our laboratory and other groups regarding the optimal isolation procedures and describe the updated molecular characteristics of VSELs.
Animals ; Cell Lineage ; Cell Separation/*methods ; Embryonic Stem Cells/*cytology/metabolism ; Hematopoietic Stem Cells/*cytology/metabolism ; Humans ; Mesenchymal Stromal Cells/*cytology/metabolism ; Pluripotent Stem Cells/cytology/metabolism

Somatostatin (SST) is an inhibitory polypeptide hormone that plays an important role in a variety of biological processes. Somatostatin receptor 2 (SSTR2) is the most widely expressed somatostatin receptor. However, the specific cell types expressing Sstr2 in the tissues have not been investigated. In this study, we detected the expression pattern of SSTR2 protein in mouse at different development stages, including the embryonic 15.5 days and the postnatal 1, 7, 15 days as well as 3 and 6 months, by multicolour immunofluorescence analyses. We found that Sstr2 was expressed in some specific cells types of several tissues, including the neuronal cells and astrocytes in the brain, the mesenchymal cells, the hematopoietic cells, the early hematopoietic stem cells, and the B cells in the bone marrow, the macrophages, the type Ⅱ alveolar epithelial cells, and the airway ciliated cells in the lung, the epithelial cells and the neuronal cells in the intestine, the hair follicle cells, the gastric epithelial cells, the hematopoietic stem cells and the nerve fibre in the spleen, and the tubular epithelial cells in the kidney. This study identified the specific cell types expressing Sstr2 in mouse at different developmental stages, providing new insights into the physiological function of SST and SSTR2 in several cell types.
Mice ; Animals ; Receptors, Somatostatin/metabolism* ; Hematopoietic Stem Cells/metabolism* ; Epithelial Cells

This study was to establish an iron overload bone marrow (BM) model by co-culturing the mononuclear cells from BM with iron, and investigate its hematopoiesis changes. The iron overload model was set up by adding different concentration of ferric citrate (FAC) into the mononuclear cells from BM and culturing for different time, and the model was confirmed by detecting labile iron pool (LIP). Then the apoptosis of hematopoietic cells, ability of hematopoietic colony forming (CFU-E, BFU-E, CFU-GM and CFU-mix) and percentage of the CD34(+) cells of the BM cells all were determined. The changes of these indexes were tested after the iron-overloaded BM was treated with deferasirox (DFO). The results showed that after BM cells were cultured with FAC at different concentrations for different time, the LIP increased in time-and concentration-dependent manners. The intracellular LIP reached maximum level when cultured at 400 µmol/L of FAC for 24 hours. The detection of BM cell hematopoietic function found that the apoptotic rate of the FAC-treated cells (24.8 ± 2.99%) increased significantly, as compared with normal control (8.9 ± 0.96%)(p < 0.01). The ability of hematopoietic colony forming in FAC-treated cells decreased markedly, as compared with normal control (p < 0.05). The percentage of CD34(+) cells of FAC-treated cells (0.39 ± 0.07%) also decreased significantly, as compared with normal control (0.91 ± 0.12%)(p < 0.01). And these changes could be alleviated by adding DFO. It is concluded that the iron-overloaded model has been set by adding iron into the mononuclear cells from BM in vitro, and the hematopoietic function of iron-overloaded BM is deficient. These changes can be alleviated by removing the excess iron from the BM cells through treating with DFO. These findings would be helpful to further study the mechanism of iron-overload on the hematopoiesis of BM and also useful to find the way to treat iron-overload patients with hematopoietic disorders.
Bone Marrow Cells ; cytology ; Cells, Cultured ; Hematopoiesis ; Hematopoietic Stem Cells ; cytology ; Humans ; Iron ; metabolism ; Iron Overload

Reactive oxygen species (ROS) are bioactive oxygen molecules produced after exposure to exogenous oxidants or endogenously through cellular aerobic metabolism. Hematopoietic stem cells (HSC) are multipotent, self-renewing stem cells residing in hematopoietic tissues. Recent studies show that an abnormal increase in ROS production is associated closely with HSC senescence. Many signaling molecules such as FoxOs, ATM, mTOR, TSC1, Bmi1 and AKT play a significant role in ROS-induced HSC senescence. The roles of p53-p21 and p16-Rb pathways can induce hematopoietic dysfunction and lead to ROS-induced HSC senescence. This review summarizes the recent progress of studies on ROS-induced HSC senescence, and further elaborates the potential signaling molecules and pathways, aiming to provide a new target and thread for clinical treatment.
Animals ; Cellular Senescence ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Reactive Oxygen Species ; metabolism ; Signal Transduction

Ex vivo expansion of hematopoietic progenitor cells (HPCs) is valuable for clinical application, however, traditional ex vivo culture negatively affects long-term hematopoietic reconstitution ability. In the hematopoietic system, the expression of Notch receptors and their ligands has been widely reported. Active Notch signal inhibits the differentiation of HSCs while promotes their expansion, suggesting that ex vivo expansion of hematopoietic progenitor cells could be enhanced by manipulating Notch signal pathways. In this article the Notch signal pathways, Notch signal and maintenance of hematopoietic progenitor cells, Notch signal and expansion of hematopoietic progenitor cells and molecular mechanism of Notch signal maintaining undifferentiation of hematopoietic progenitor cells were reviewed.
Animals ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Receptors, Notch ; metabolism ; Signal Transduction