Neural ganglioside GD2 identifies a subpopulation of mesenchymal stem cells in umbilical cord.

In contrast to hematopoietic stem cells, there is still a lack of definitive cell markers for specific isolation and identification of mesenchymal stem cells (MSCs). Thus a homogenous population of MSCs is only obtained after several passages, when multilineage potential or other distinctive features of very early progenitors may be already somewhat compromised. Recently a novel surface marker the neural ganglioside GD2 has been reported to distinguish MSCs from all other cells within marrow.

Exogenous Nanog alleviates but is insufficient to reverse embryonic stem cells differentiation induced by PI3K signaling inhibition.

PI3K signaling pathway plays a significant role in embryonic stem cells (ES cells) self-renewal. Overexpression of Nanog maintains mouse ES cells pluripotency independent of leukemia inhibitory factor (LIF). However, little is known about the effect of PI3K signaling pathway on ES cells with Nanog overexpression.

Identification of genes regulated by nanog which is involved in ES cells pluripotency and early differentiation.

Nanog plays an important role in embryonic stem (ES) cells pluripotency and self-renewal, yet the precise mechanism through which Nanog accomplishes this important function remains unclear. To understand comprehensive molecular mechanism by which Nanog mediates, we identified genome-wide molecular changes upon silencing Nanog in ES cells by using microarray technology. In order to downregulate Nanog expression efficiently, four siRNAs were designed on the basis of the conserved Nanog sequence and their effects on the Nanog expression were tested.

[Neovascularization potential of mobilized peripheral mononuclear cells from diabetes patients].

Objective: To determine whether mobilized peripheral blood mononuclear cells (M-PBMNCs) obtained from patients with diabetes was impaired in therapeutic neovascularization in limb ischemia, and to explore the pathological mechanisms of the impairment.

Methods: Endothelial progenitor cells (EPC) were cultured in EGM-2MV, and then characterized by uptake of 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindocarbocyanine-labeled acetylated low density lipoprotein (Dil-AcLDL) and binding of ulex europaeus agglutinin (UEA). The number of EPC was compared between M-PBMNCs obtained from diabetic patients and those from normal subjects.

Enhancement of neovascularization with mobilized blood cells transplantaion: supply of angioblasts and angiogenic cytokines.

We have recently provided evidence that transplantation of G-CSF mobilized peripheral blood mononuclear cells (M-PBMNCs) improves limb ischemia in diabetic patients. This method represents a simple, safe, effective, and novel therapeutic approach for diabetic ischemia. Here we investigated the mechanisms by which mobilized blood cells transplantation improves limb ischemia.

Therapeutic neovascularization for peripheral arterial diseases: advances and perspectives.

Recently, with the better understanding of the mechanisms of neovascularization, many new therapeutic approaches to enhance neovascularization have emerged. Of these diverse emerging methods, use of growth factors and cells are the two major ones. This review will provide an update on the present understanding of the basic mechanisms of angiogenesis, vasculogenesis, and arteriogenesis, as a basis for designing future pro-neovascularization treatments.

Molecular mechanisms involved in self-renewal and pluripotency of embryonic stem cells.

Embryonic stem cells (ES cells) are derived from inner cell mass (ICM). The self-renewal and pluripotency are the main specificities of ES cells, which are likely to reveal a deeper understanding of human cellular biology and which are considered to be promising sources for cell therapy to treat patients with degenerative diseases in clinical. Growth of ES cells as a pluripotent population requires a balance between survival, proliferation, and self-renewal signals.

Impaired therapeutic vasculogenesis by transplantation of OxLDL-treated endothelial progenitor cells.

Previous in vitro studies have revealed that oxidized low density lipoprotein (OxLDL) has negative effects on the proliferation and activity of endothelial progenitor cells (EPCs). Here, we evaluated the effect of OxLDL on the therapeutic potential of EPCs in ischemia-induced neovascularization. EPCs derived from mobilized human peripheral blood mononuclear cells were cultured without or with OxLDL before transplantation.

Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells.

Aim: To investigate whether the prophylactic local delivery of mobilized peripheral blood mononuclear cells (M-PBMNC) could prevent peripheral microangiopathy in diabetic nude mice.

Methods: Diabetic nude mice were induced with intraperitoneal injections of streptozotocin. With the time course of diabetes, we detected the capillary and arteriole density of mice adductor muscles by immunohistopathy.

[Expression of recombinant human hemangiopoietin and preparation of its polyclonal antibody].

Aim: To express the recombinant fusion protein of hemangiopoietin (HAPO) and prepare the rabbit-anti-human HAPO polyclonal antibody.

Methods: The sequence encoding HAPO was amplified by PCR and cloned into plasmid pET32c to construct recombinant prokaryotic expression system. The recombinant expression vectors were identified by enzyme digestion analysis and transformed into E.

Endothelial progenitor cells transfected with PDGF: cellular and molecular targets for prevention of diabetic microangiopathy.

Microvascular insufficiency represents a major cause of end-organ failure among diabetics. Prevention at early stage of disease is therefore necessary and is a focus of current investigations. Progression of diabetes is complicated by endothelial cell apoptosis as well as occlusion of arteriole and capillary leading to microvascular rarefaction.

G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capability.

Background: Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization.

Objective: This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment.

Statins, nitric oxide and neovascularization.

Several landmark clinical trials suggest that 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have additional cardiovascular protective activity that may function independently of their ability to lower serum cholesterol. The cardiovascular protective effects of statins are partly caused by the activation of postnatal neovascularization. At therapeutic doses, statins promote proliferation, migration and survival of endothelial cells, induce mobilization and differentiation of bone marrow-derived endothelial progenitor cells by stimulating the serine/threonine protein kinase Akt (also known as protein kinase B) and nitric oxide (NO) signal pathway.

Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase.

Oxidized low density lipoprotein (OxLDL) is one of the most important risk factors of cardiovascular disease. Here, we study the impact of OxLDL on endothelial progenitor cells (EPCs) and determine whether OxLDL affects EPCs by an inhibitory effect on endothelial nitric oxide synthase (eNOS). It was found that OxLDL decreased EPC survival and impaired its adhesive, migratory, and tube-formation capacities in a dose-dependent manner.

Matrix metalloproteinases in bone marrow: roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies.

Turnover balance of extracellular matrix (ECM) is a prerequisite for the structural and functional homeostasis of bone marrow (BM) microenvironment. The role of ECM in physiologic hematopoiesis and its pathologic change in hematopoietic malignancies are very important and under extensive investigation. Accumulating evidence suggests that matrix metalloproteinases (MMPs), a family of zinc-dependent proteinases, take an active part in the physiological and pathological hematopoiesis through remodeling the ECM in BM hematopoietic microenvironment.

Autologous transplantation of granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells improves critical limb ischemia in diabetes.

Objective: To assess the application of autologous transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (PBMNCs) in the treatment of critical limb ischemia (CLI) of diabetic patients and to evaluate the safety, efficacy, and feasibility of this novel therapeutic approach.

Research Design And Methods: Twenty-eight diabetic patients with CLI were enrolled and randomized to either the transplant group or the control group. In the transplant group, the patients received subcutaneous injections of recombinant human G-CSF (600 microg/day) for 5 days to mobilize stem/progenitor cells, and their PBMNCs were collected and transplanted by multiple intramuscular injections into ischemic limbs.

[Expression of alternatively spliced isoforms of platelet endothelial cell adhesion molecule-1 of embryonic stem cells during vasculogenesis and angiogenesis].

Objective: To study the expression of alternatively spliced isoforms of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) of embryonic stem cells (ES cells) during vasculogenesis and angiogenesis.

Methods: Mouse ES cells of the line J1 were cultured. Another ES cells were cultured in differentiation medium to induce the formation of embryonic bodies (EBs).

Kinetic expression of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) during embryonic stem cell differentiation.

Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) is widely used as a marker during vasculogenesis and angiogenesis from embryonic stem (ES) cells. However, the expression of PECAM-1 isoforms in ES cells has not been determined. The present study was designed to determine the role of PECAM-1 isoforms during in vitro endothelial differentiation of ES cells.

Akt signaling and its role in postnatal neovascularization.

Postnatal neovascularization has been known to be involved in not only angiogenesis but also vasculogenesis. Several lines of evidence suggest a link between neovascularization and Akt, a family member of serine/threonine protein kinases. Akt phosphorylates endothelial NO synthase (eNOS) and thereby enhances endothelial NO synthesis and influences postnatal vessel growth.

Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation.

The endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization and have been used for attenuating ischemic diseases. However, EPCs from umbilical cord blood (CB) were not well understood and the homing mechanisms of EPCs remain unclear. To determine the potential application of CB-derived EPCs, we established a culture system to induce the differentiation of CB cells into EPCs.

Hemangiopoietin inhibits apoptosis of MO7e leukemia cells through phosphatidylinositol 3-kinase-AKT pathway.

Hemangiopoietin (HAPO) is a growth factor that significantly stimulates proliferation and survival of the primitive cells of hematopoietic and endothelial lineages. To determine the mechanism of action of HAPO, the anti-apoptotic activity and signal transduction pathway of HAPO were investigated using a factor-dependent leukemia cell line, the MO7e cells. Recombinant human HAPO (rhHAPO) was produced in Escherichia coli and purified by a series of column chromatography with a purity of more than 95%.

Autologous transplantation of peripheral blood stem cells as an effective therapeutic approach for severe arteriosclerosis obliterans of lower extremities.

Treatment of severe arteriosclerosis obliterans of lower extremities (ASOLE) remains a clinical challenge. To develop a more effective approach, we evaluated the clinical efficacy of autologous transplantation of mobilized peripheral blood stem cells (PBSCs) in 5 patients with ASOLE. The patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF, 600 micro g/day) for 5 consecutive days.