The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and alpha-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and yen a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.
Cornea/*pathology ; Corneal Ulcer/*pathology ; Hematopoietic Stem Cells/*pathology ; Humans ; Multipotent Stem Cells/*pathology ; Research Support, Non-U.S. Gov't

Cell Proliferation ; Colony-Forming Units Assay ; Glioma ; pathology ; Hematopoietic Stem Cells ; pathology ; Humans ; Stem Cells ; cytology ; metabolism

This is the case of a 71 year old male who developed multiple myeloma (MM) and chronic myelogenous leukemia (CML) within a two year period. The patient initially presented with osteolytic lesions of the lumbar spine, and following the initial work-up a diagnosis of multiple myeloma with an IgG kappa paraproteinemia was made and appropriate treatment was given. Two years later the patient developed a progressively worsening leukocytosis which was found to be due to Philadelphia Chromosome (Ph1) positive CML. The occurrence in the same patient of two distinct hematologic malignancies suggests a neoplastic transformation of a pluripotent stem cell. A review of the literature appears to support the existence of a relationship between MM and CML as well as a relationship between MM and the myeloproliferative disorders.
Aged ; Case Report ; Cell Transformation, Neoplastic/pathology ; Hematopoietic Stem Cells/pathology ; Human ; Leukemia, Myeloid, Chronic/*pathology ; Male ; Multiple Myeloma/*pathology

Bone marrow mesenchymal stromal cells (MSCs) have been implicated in the microenvironmental support of hematopoietic stem cells (HSCs) and often co-transplanted with HSCs to facilitate recovery of ablated bone marrows. However, the precise effect of transplanted MSCs on HSC regeneration remains unclear because the kinetics of HSC self-renewal in vivo after co-transplantation has not been monitored. In this study, we examined the effects of intrafemoral injection of MSCs on HSC self-renewal in rigorous competitive repopulating unit (CRU) assays using congenic transplantation models in which stromal progenitors (CFU-F) were ablated by irradiation. Interestingly, naive MSCs injected into femur contributed to the reconstitution of a stromal niche in the ablated bone marrows, but did not exert a stimulatory effect on the in-vivo self-renewal of co-transplanted HSCs regardless of the transplantation methods. In contrast, HSC self-renewal was four-fold higher in bone marrows intrafemorally injected with beta-catenin-activated MSCs. These results reveal that naive MSCs lack a stimulatory effect on HSC self-renewal in-vivo and that stroma must be activated during recoveries of bone marrows. Stromal targeting of wnt/beta-catenin signals may be a strategy to activate such a stem cell niche for efficient regeneration of bone marrow HSCs.
Animals ; Bone Marrow/metabolism/pathology ; Hematopoietic Stem Cell Mobilization ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/pathology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Radiation Chimera ; Regeneration ; Stem Cell Niche/metabolism/pathology ; Stromal Cells/*metabolism/pathology ; *Transplantation Conditioning ; beta Catenin/*metabolism

Recently there are increasing evidence of the existence of an immune-mediated endothelial-cell injury in the acute graft-versus-host disease (aGVHD). Endothelial cells are an important target in the process of GVHD immune attacking, and vascular end thelial injure is an early event of tissue injury caused by aGVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Biomarkers for endothelial damage were consisted with endothelia injury, which may be considered a valuable marker to confirm GVHD diagnosis. The endothelial cell phenotype differs between organs, which results in organ-dependent differences for the involved organs when GVHD occurring. Although the endothelial cells play an impartant tole in process of aGVHD occurence, a further research to better characterize its role in allo-HSCT is needed. This review focusses on the research progress of aGVHD after allo-HSCT and endothelial-cell injury, as well as is markers so as to provide corresponding strategies and targets for the prevent and treatment of a GVHD.
Biomarkers ; Endothelial Cells ; pathology ; Graft vs Host Disease ; physiopathology ; Hematopoietic Stem Cell Transplantation ; Humans

Hematopoietic Stem Cells ; Histone-Lysine N-Methyltransferase ; Histones ; Humans ; Leukemia ; pathology

OBJECTIVETo observe the differentiation of bone marrow stem cells in rat hepatic fibrogenesis environment into hepatocytes.

METHODSRat hepatic fibrosis was induced by subcutaneous injection of CCl4. Bone marrow stem cells with Thy positive, CD3 and CD45RA negative were enriched from the bone marrow by fluorescence-activated cell sorting. The bone marrow stem cells were labeled with PKH26-GL, and then autotransplanted. After six weeks, albumin, ck8 and a-smooth muscle actin expression were determined by immunocytochemistry.

RESULTSThe PKH26-GL labeled cells expressed albumin and ck8, but did not express a-smooth muscle actin in hepatic fibrogenesis environment.

CONCLUSIONBone marrow stem cells in hepatic fibrogenesis environment can differentiate into hepatocytes, but can't differentiate into myofibroblasts

Animals ; Bone Marrow Cells ; pathology ; Cell Differentiation ; physiology ; Environment ; Hematopoietic Stem Cells ; pathology ; Hepatocytes ; pathology ; Liver Cirrhosis ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

The objective of this study was to investigate the expressions of TPO receptor (c-mpl) proteins on CD34 positive bone marrow cells (CD34+ BMCs), platelets and the expression of c-mpl mRNA in bone marrow cells of the patients with polycythemia vera (PV). The expressions of c-mpl proteins on CD34+ bone marrow hematopoietic cells of 13 PV patients and 15 normal controls were assessed by bicolor flow cytometry and the expressions of c-mpl proteins on platelets of 15 PV patients and 15 normal controls were assessed by monocolor flow cytometry, and the expressions of c-mpl mRNA in bone marrow hematopoietic cells (BMHCs) were assessed by RT-PCR. The results showed that no difference was found between the expression of c-mpl proteins on CD34+ BMHCs of PV patients (0.99% +/- 0.14%) and that of normal controls (0.92% +/- 0.12%) (p > 0.05). There was no difference too between the expression of c-mpl protein on platelets in PV patients (20.33% +/- 4.84%) and that in normal controls (23.50% +/- 3.64%) (p > 0.05). No difference between the expression of c-mpl mRNA in BMHCs of PV patients and that in normal controls was seen. In conclusion, the expressions of c-mpl proteins on CD34+ BMHCs, platelets and c-mpl mRNA in BMHCs of PV patients were not obviously abnormal.
Antigens, CD34 ; analysis ; Blood Platelets ; metabolism ; Bone Marrow Cells ; metabolism ; pathology ; Hematopoietic Stem Cells ; metabolism ; pathology ; Humans ; Polycythemia Vera ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Receptors, Thrombopoietin ; metabolism

To investigate the effects of sera on the growth of single CD34(+) cells from patients with paroxysmal nocturnal hematoglobinuria (PNH), sera from both PNH patients and normal individuals were added separately to the single cell culture system and semi-solid colony formation system. The growth of the normal CD34(+) and PNH CD34(+) CD59(+) and CD34(+) CD59(-) cells was evaluated. No growth difference was found for growth of the normal CD34(+) and PNH CD34(+) CD59(+) cells when PNH or normal sera were added to the culture media in either single cell culture or colony formation culture. While no difference was detected for single PNH CD34(+) CD59(-) cells growth when PNH or normal sera were added, more colonies were observed in semi-solid culture with PNH sera. A conclusion was reached that compared with those from normal controls, the sera from PNH patients had no significant influence on single hematopoietic stem/progenitor cells derived from normal subjects and from PNH patients, but the PNH sera might promote the colony formation of the CD34(+) CD59(+) cells in semi-solid culture
Antigens, CD34 ; analysis ; Blood Proteins ; pharmacology ; CD59 Antigens ; analysis ; Cell Division ; drug effects ; Cells, Cultured ; Hematopoietic Stem Cells ; drug effects ; pathology ; Hemoglobinuria, Paroxysmal ; immunology ; pathology ; Humans

BACKGROUNDVascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis. But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not yet fully understood.

METHODSDouble-transgenic mice knockout of LDL receptor gene (LDL -/-) and expressing ubiquitously green fluorescent protein (GFP) were obtained by cross-breeding LDL -/- mice with the GFP-expressing transgenic mice. LDL -/- mice (22 - 24 weeks of age) fed high fat diet containing 1.25% (w/w) cholesterol were subjected to 9Gy irradiation and received bone marrow (BM) cells from the double-transgenic mice. Four weeks later, a nonconstrictive cuff was placed around the right femoral artery. After another 2 weeks, both right and left femoral arteries were harvested and subjected to histochemical analysis. Apoptosis was analyzed in situ using TUNEL assay.

RESULTSTwo weeks after cuff placement, atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells. The tissue stained with anti-alpha smooth muscle actin (SMA) antibody, showed a number of SMA-positive cells in the intimal lesion area. They were also positive for GFP, indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions. Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP. The intima and media showed a large number of TUNEL-positive signals after 2 weeks cuff injury, indicating the presence of apoptosis in vascular remodeling.

CONCLUSIONSAtherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular injury under the hypercholesterolemic conditions. Our data also clearly indicate that bone marrow-derived cells differentiated to smooth muscles and endothelial cells in the formation of these lesions in the presence of hypercholesterolemia.

Animals ; Apoptosis ; Atherosclerosis ; pathology ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cell Movement ; Endothelial Cells ; pathology ; Female ; Hematopoietic Stem Cells ; pathology ; Mice ; Mice, Inbred C57BL ; Muscle, Smooth, Vascular ; pathology ; Receptors, LDL ; physiology ; Tunica Intima ; pathology ; Tunica Media ; pathology