Hematopoietic development is characterized by the dynamic generation of hematopoietic stem/progenitor cells during embryogenesis, and afterward, the maintaining of hematopoietic homeostasis in adult. Mouse model has been appreciated valuable for dissecting the regulatory mechanisms of hematopoietic development. As an important cytokine playing pivotal and versatile roles in the regulation of hematopoiesis, transforming growth factor-beta (TGF-beta) attracts more and more attention. In particular, gene targeting by homologous recombination provides a key means for systematic evaluation of how TGF-beta signaling is involved in hematopoiesis under physiological conditions. To further illustrate the functions and possible mechanisms of TGF-beta in hematopoietic development, hematopoietic phenotypes of targeted mutations and/or dominant negative transgenes of molecules within the TGF-beta signaling pathway are categorized and discussed in this review.
Animals ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; physiology ; Humans ; Signal Transduction ; physiology ; Transforming Growth Factor beta ; physiology

Dipeptidyl peptidase-4 (DPP-4) is a protease that cleaves the peptides with alanine, praline, or other selective amino acids at the N-terminal penultimate position. The substrates of DPP-4 include many chemokines, colony-stimulating factors, and interleukins. Recent research has shown that DPP-4 can affect the hematopoietic stem and progenitor cells and transplantation by truncating the granulocyte colony stimulating factor. However, its regulatory effect on DPP-4 and most peptides truncation are still unknown. This review summarizes the recent advances in the DPP-4 research.
Dipeptidyl Peptidase 4 ; physiology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Humans

MicroRNAs (miRNAs) are a family of 21-25 nucleotide small nonprotein-coding RNAs. They regulate gene expression at post-transcriptional level by mRNA degradation or translation repression. Hematopoiesis is one of the most important highly regulated multistage process, which includes orderly turn-on and turn-off of many genes; any wrong modulation may result in blood diseases. Several miRNAs have been found to be involved in hematopoiesis and hematopoietic tumor genesis.
Blood Cells ; physiology ; Cell Differentiation ; Hematologic Neoplasms ; pathology ; Hematopoiesis ; physiology ; Humans ; MicroRNAs ; physiology

Hematopoietic stem cell transplantation (HSCT) is an important mean for clinical treatment to many of hematological diseases, malignant diseases, hereditary diseases and autoimmune diseases. Whether the implanted hematopoietic stem cells (HSC) can home to bone marrow (BM) smoothly and reconstitute the hematopoiesis is the key to successful HSCT. With the cognition of HSC homing mechanism, the visual observation of HSC homing to BM is attracting more and more attention and helps to clarify the micro-dialogue between HSC and BM microenvironment. In recent years, with the development of imaging technology, confocal laser scanning microscope (CLSM) and two-photon microscope are able to make 3D reconstruction and real-time observation of the tissue or cells. Researches on HSC homing process visibly become reality. In this article the methods of visual research and their application in HSC homing observation are reviewed.
Cell Movement ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; cytology ; physiology ; Humans ; Stem Cell Niche ; physiology

As the progenitor of most cell components in the hematopoietic microenvironment, mesenchymal stem cells (MSC) exhibit self-renewal and multilineage differentiation capacity. Through direct interaction with hematopoietic cells, secreting extracellular matrix and factors, MSC maintain the integrity of hematopoietic microenvironment and regulate hematopoiesis accurately. This review summarized the function of MSC in hematopoietic regulation, such as secretion of cytokines supporting hematopoiesis, MSC expression and adhesion molecules interacting with hematopoietic cells, and supportive effects of transplantation combining MSC with HSC on hematopoietic reconstruction, and its clinical perspectives.
Cell Communication ; Cytokines ; biosynthesis ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; physiology ; Mesenchymal Stromal Cells ; physiology

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*

This study was aimed to investigate the biological characteristics of osteoblasts and their hematopoietic supportive function by using human fetal osteoblastic cell line 1.19 (hFOBs) as a model. The pluripotency markers (Oct-4, Rex-1, hTERT) of hFOBs were analyzed by RT-PCR, the multilineage differentiation experiments were conducted in vitro. Flow cytometry (FCM) was used to identify the surface markers of hFOBs, and RT-PCR was used to analyze their hematopoietic cytokine expression in comparison with bone marrow mesenchymal stem cell (BM-MSC). The results showed that hFOBs expressed several ESC pluripotency markers including Oct-4 and Rex-1, except hTERT. Moreover, hFOBs could also undergo multilineage differentiation into the mesodermal lineages of adipocytic cell types in addition to its predetermined pathway, the mature osteoblast. Both hFOBs and BM-MSC expressed CD44, CD73 (SH3), CD105 (SH2) and CD90 (Thy1), and lack expression of CD34, CD45, or HLA-DR surface molecules. In addition, both hFOBs and BM-MSC expressed SCF, IL-6, and SDF-1alpha mRNA, but only hFOBs could express GM-CSF and G-CSF. It is concluded that human fetal osteoblastic cell line 1.19 may provide a good model to study the osteoblastic regulation role in hematopoiesis in vitro.
Cell Differentiation ; physiology ; Cell Line ; Fetus ; Hematopoiesis ; physiology ; Humans ; Mesenchymal Stromal Cells ; cytology ; physiology ; Models, Biological ; Osteoblasts ; cytology ; physiology

Membrane microparticles are shed from the plasma membrane of most eukaryotic cells when these cells were undergone activation or apoptosis, and released into the extracellular environment. Their composition depends on the cellular origin and processes triggering their formation. Several lines of evidence suggest that membrane microparticles might be able to facilitate cell-cell cross-talk and play an important roles in the regulation of survival, proliferation, differentiation, adhesion and chemotaxis of hematopoietic cells. Here, the components, mechanism of formation and the regulatory roles of membrane microparticles in hematopoiesis were reviewed.
Caveolae ; metabolism ; physiology ; Cell Membrane ; metabolism ; physiology ; Hematopoiesis ; physiology ; Humans ; Models, Biological ; R-SNARE Proteins ; metabolism ; physiology

BACKGROUNDHematopoietic growth factor (HGF) is indispensable to hematopoiesis in the body. The proliferation and differentiation of hematopoietic cells must rely on the existence and stimulation of HGF. This study investigated the effect of catechin, an active component extracted from Spatholobus suberectus Dunn (SSD), on bioactivity of granulocyte-macrophage colony-stimulating activity (GM-CSA), burst-promoting activity (BPA) and megakaryocyte colony-stimulating activity (MK-CSA) in spleen condition medium (SPCM) of mice to clarify the hematopoietic mechanism of catechin and SSD.

METHODSSpleen cells of mice were separated and spleen condition medium (SPCM) was prepared from spleen cell culture. Bone marrow cells of mice were separated and cultured in a culture system including 10% (v/v) SPCM (induced by catechin in vivo or ex vivo) for 6 days. Granulocyte-macrophage colony forming units (CFU-GM), erythrocyte burst-colony-forming units (BFU-E) and megakaryocyte colony-forming units (CFU-Meg) formation were employed to assay the effects of different treatment on the bioactivity of GM-CSA, BPA and MK-CSA in SPCM.

RESULTSSPCM induced by 100 mg/L catechin ex vivo could promote the growth of CFU-GM, BFU-E and CFU-Meg, which indicated that catechin could stimulate the production of GM-CSA, BPA and MK-CSA in SPCM. SPCM prepared at the fourth day of spleen cell culture showed the best stimulating activity. The bioactivity of GM-CSA, BPA and MK-CSA in the SPCM prepared after intraperitoneally injecting catechin into mice was also increased. The number of CFU-GM, BFU-E and CFU-Meg gradually increased as the dose of catechin increased and the time of administration prolonged. CFU-GM, BFU-E and CFU-Meg of the high-dose catechin group were significantly higher than those of the control group (P < 0.01) and reached the maximum at the seventh day after administration.

CONCLUSIONSThis study suggests that catechin extracted from the active acetic ether part of Spatholobus suberectus Dunn can regulate hematopoiesis by inducing bioactivity of GM-CSA, BPA and MK-CSA in SPCM of mice. This may be one of the mechanisms for the hematopoietic-supportive effect of catechin and Spatholobus suberectus Dunn.

Animals ; Catechin ; pharmacology ; Granulocyte-Macrophage Colony-Stimulating Factor ; physiology ; Hematopoiesis ; drug effects ; Interleukin-3 ; physiology ; Mice ; Thrombopoietin ; physiology

Cytokines such as erythropoietin (EPO) and thrombopoitein (TPO) and so on, which stimulate hematopoiesis, can regulate self-renewal, proliferation, differentiation, maturation and programmed cell death of hematopoietic cells through specifically binding to surface receptors. Recently random phage display peptide libraries and other screening methods have been used to isolate mimetic including small peptides and non-peptides molecules, which can mimic the same effects as cytokines, such as EPO and TPO, and demonstrate the similar potency and activity as EPO and TPO in a panel of in vitro biological assays and in animal experiments. These approaches are critical to further research of interactive mechanisms between cytokine and receptor, receptor activation and rational design of other desired cytokine mimetic. This review concisely introduced recent advances in research on mimetic of EPO, TPO and other cytokines and future directions.
Animals ; Cytokines ; pharmacology ; Erythropoietin ; pharmacology ; Hematopoiesis ; drug effects ; physiology ; Humans ; Peptide Library ; Peptides ; pharmacology ; Thrombopoietin ; pharmacology