Publications (12)43.52 Total impact
-
Article: Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow, heart, liver, muscle, lung, derma, kidney, and fat
[show abstract] [hide abstract]
ABSTRACT: Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1+CD34− postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level in vitro, and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1+CD34− PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1+CD34− PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the “stem cell plasticity” found in multiple human tissues. In addition, as fetal BM-derived Flk1 + CD34− PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings in vitro. Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.Frontiers of Medicine in China 04/2012; 1(2):185-191. -
Article: [Multipotency of adult stem cells derived from human amnion].
[show abstract] [hide abstract]
ABSTRACT: Adult stem cells are drawing more and more attention due to the potential application in degenerative medicine without posing any moral problem. There is growing evidence showing that the human amnion contains various types of adult stem cell. Since amniotic tissue is readily available, it has the potential to be an important source of regenerative medicine material. In this study we tried to find multipotent adult stem cells in human amnion. We isolated stem cells from amniotic mesenchymal cells by limiting dilution assay. Similar to bone marrow derived mesenchymal stem cells, these cells displayed a fibroblast like appearance. They were positive for CD105, CD29, CD44, negative for haematopoietic (GlyA, CD31, CD34, CD45) and epithelial cell (pan-CK) markers. These stem cells had the potential to differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells and neural cells at the single-cell level depending on the culture conditions. They had the capacity for self-renewal and multilineage differentiation even after being expanded for more than 30 population doublings in vitro. So they may be an ideal stem cell source for inherited or degenerative diseases treatment.Sheng wu gong cheng xue bao = Chinese journal of biotechnology 06/2009; 25(5):754-60. -
Article: Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model.
[show abstract] [hide abstract]
ABSTRACT: Human mesenchymal stem cells (hMSCs) can home to tumor sites and inhibit the growth of tumor cells. Little is known about the underlying molecular mechanisms that link hMSCs to the targeted inhibition of tumor cells. In this study, we investigated the effects of hMSCs on two human hepatoma cell lines (H7402 and HepG2) using an animal transplantation model, a co-culture system and conditioned media from hMSCs. Animal transplantation studies showed that the latent time for tumor formation was prolonged and that the tumor size was smaller when SCID mice were injected with H7402 cells and an equal number of Z3 hMSCs. When co-cultured with Z3 cells, H7402 cell proliferation decreased, apoptosis increased, and the expression of Bcl-2, c-Myc, proliferating cell nuclear antigen (PCNA) and survivin was downregulated. After treatment with conditioned media derived from Z3 hMSC cultures, H4702 cells showed decreased colony-forming ability and decreased proliferation. Immunoblot analysis showed that beta-catenin, Bcl-2, c-Myc, PCNA and survivin expression was downregulated in H7402 and HepG2 cells. Taken together, our findings demonstrate that hMSCs inhibit the malignant phenotypes of the H7402 and HepG2 human liver cancer cell lines, which include proliferation, colony-forming ability and oncogene expression both in vitro and in vivo. Furthermore, our studies provide evidence that the Wnt signaling pathway may have a role in hMSC-mediated targeting and tumor cell inhibition.Cell Research 05/2008; 18(4):500-7. · 8.19 Impact Factor -
Article: Elevated tumor necrosis factor-alpha suppresses TAZ expression and impairs osteogenic potential of Flk-1+ mesenchymal stem cells in patients with multiple myeloma.
[show abstract] [hide abstract]
ABSTRACT: One of the clinical features of multiple myeloma (MM) is the occurrence of skeletal events, which are characterized by increased bone resorption and decreased bone formation. In contrast to enhanced osteoclastogenesis, little is known about the mechanism of impaired bone formation in MM. Because TAZ, a Runx2/Cbfa1 transcriptional co-activator, has recently been shown to modulate mesenchymal stem cell (MSC) differentiation in favor of osteoblast differentiation, we investigated whether the regulation of TAZ expression played a role in the decreased bone formation of MM. We isolated and purified Flk-1(+)CD31(-)CD34(-) cells with MSC characters from bone marrow (BM) of myeloma patients and healthy donors. We found the osteogenic potential of the MSCs from myeloma patients decreased significantly, and TAZ expression of these cells was lower than that of healthy donors. Human myeloma cell lines (HMCLs) and CD138(+) myeloma cells (MCs) from myeloma patients inhibited osteogenesis of the MSCs from healthy volunteers, which were accompanied by a reduced TAZ expression and elevated TNF-alpha concentration in the supernatant of co-culture systems. The repressed osteogenesis and TAZ expression were both partially restored by neutralization of TNF-alpha. Thus, the decreased osteogenic potential of MSCs of myeloma patients was in part due to TNF-alpha suppressed TAZ expression.Stem Cells and Development 01/2008; 16(6):921-30. · 4.46 Impact Factor -
Article: Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells.
[show abstract] [hide abstract]
ABSTRACT: Mesenchymal stem cells (MSCs) have profound immunomodulatory functions both in vitro and in vivo. However, their effects on the differentiation of dendritic cells (DCs) are unknown. In this study, we employed an in vitro model to investigate the effects of human MSCs on the development of DCs. CD34(+) cells isolated from cord blood were cultured under conventional DC(cDC) or plasmacytoid DC (pDC) differentiation conditions, in the presence or absence of MSCs or their conditioned medium. Here we show that both MSCs and their conditioned medium dramatically increased the numbers of cells generated under either condition. The percentage of cells with the cDC phenotype is significantly reduced in the presence of MSCs or their conditioned medium, whereas the percentage of pDC increased. The capacity of cDCs from MSCs or their conditioned medium-treated CD34(+) cells to stimulate allogeneic T cells was weakened. Furthermore, MSCs can skew the DC function from cDC to pDC, thus biasing the immune system toward Th2 and away from Th1 responses. Blocking the prostaglandin E(2) (PGE(2)) synthesis of MSCs can reverse most of these influences of MSCs on DCs differentiation and function. Therefore, MSCs can significantly influence DC development through PGE(2) production.Stem Cells and Development 11/2007; 16(5):719-31. · 4.46 Impact Factor -
Article: Senescence-unrelated impediment of osteogenesis from Flk1+ bone marrow mesenchymal stem cells induced by total body irradiation and its contribution to long-term bone and hematopoietic injury.
[show abstract] [hide abstract]
ABSTRACT: Ionizing irradiation is a common treatment for cancer patients and can result in adverse side effects affecting the bone and hematopoietic systems. Although some studies have demonstrated that ionizing radiation can induce apoptosis and senescence in hematopoietic stem cells, little is known about the effects of total body irradiation (TBI) on bone marrow (BM) mesenchymal stem cells (MSC). The objectives of this study were to determine the response of BM MSC to irradiation stress, such as cellular senescence and differentiation potential in BM MSC, and the clinical significance of these changes caused by TBI. At different time points after TBI, Flk1+ MSC were isolated from BM of male C57BL/6 mice and analyzed for colony forming units-fibroblast (CFU-F), cellular senescence-related indices and osteogenic potential. Bone histomorphometric analysis, immunohistochemical staining and bone mineral density (BMD) tests were performed to detect the effects of TBI on bone and the hematopoietic system. TBI reduced the pool of BM mesenchymal stem/progenitor cells, and altered osteoblast differentiation ability of BM MSC evidenced by changes in TAZ expression. These alterations, sustained up to 28 days post-irradiation, were independent of cellular senescence in BM MSC. Irradiated mice showed obvious bone loss and destruction of the hematopoietic osteoblastic niche, which is normally comprised of spindle-shaped N-cadherin-expressing osteoblasts. TBI treatment results in impairment in BM MSC, which might be responsible for bone loss and, at least partially, for impaired hematopoiesis.Haematologica 08/2007; 92(7):889-96. · 6.42 Impact Factor -
Article: Regulation of CXCR4 expression in human mesenchymal stem cells by cytokine treatment: role in homing efficiency in NOD/SCID mice.
[show abstract] [hide abstract]
ABSTRACT: The use of mesenchymal stem cells (MSC) for cell therapy relies on the capacity of these cells to home and engraft long-term into the appropriate target tissue(s). Homing of MSC to bone marrow (BM) post-transplantation can occur, but does so with only poor efficiency. This study was designed to evaluate the role of the SDF-1/CXCR4 axis in the homing of Flk1+ MSC derived from human fetal BM. We investigated the expression of CXCR4 in Flk1+ MSC stimulated with a cytokine cocktail and explored their homing ability 24 hours after intravenous infusion into sublethally irradiated NOD/SCID mice. The peripheral blood was analyzed and human cells in recipients' BM were quantified from 2 to 6 months after transplantation. We found that Flk1+ MSC harbored intracellular CXCR4 which can be rapidly induced to the cell surface within a few hours. Short-term (24 hours) stimulation with the cocktail of cytokines resulted in up-regulation of both cell surface and intracellular CXCR4, increasing in vitro migration capacity to SDF-1 and homing to the BM of irradiated NOD/SCID mice. Moreover, compared to non-treated cells, transplantation of cytokine-treated Flk1+ MSC resulted in faster hematologic recovery and higher levels of donor chimerism in BM. Neutralization of CXCR4 significantly reduced homing and engraftment of Flk1+ MSCs in murine BM. These results suggest that the SDF-1/CXCR4 axis plays an important role in the regulation of motility of Flk1+ MSC. Increasing CXCR4 expression might be a potential strategy to improve engraftment of MSC in BM and accelerate the recovery of hematopoiesis.Haematologica 08/2007; 92(7):897-904. · 6.42 Impact Factor -
Article: Knockdown of hypoxia-inducible factor-1alpha in breast carcinoma MCF-7 cells results in reduced tumor growth and increased sensitivity to methotrexate.
[show abstract] [hide abstract]
ABSTRACT: The hypoxia-inducible factor (HIF) 1alpha is a key regulator of the cellular response to oxygen deprivation. Specific disruption of the HIF-1 pathway is important for exploring its role in tumor biology and developing more efficient weapons to treat cancer. In this study, we stably transfected human breast tumor MCF-7 cells with short hairpin RNA expression vectors targeting HIF-1alpha. After knockdown of HIF-1alpha, hypoxia-induced expression of its target genes such as vascular endothelial growth factor, Glut-1, phosphoglycerate kinase, and P-glycoprotein were markedly attenuated. Moreover, HIF-1alpha knockdown was found to suppress the shift from S-phase to G(1) induced by hypoxia and increase drug sensitivity to methotrexate. The growth rates of HIF1alpha-knockdown tumors were drastically retarded in both subcutaneous and orthotopic xenograft models, which were accompanied by decreased angiogenesis and reduced expression of glucose transporter in tissue sections. These data demonstrate that HIF-1alpha knockdown reduces tumorigenicity of MCF-7 cells and suggest a promising combination of both anti-HIF-1 strategy and traditional chemotherapy to improve cancer treatment.Biochemical and Biophysical Research Communications 05/2006; 342(4):1341-51. · 2.48 Impact Factor -
Article: Correlation between melanoma angiogenesis and the mesenchymal stem cells and endothelial progenitor cells derived from bone marrow.
[show abstract] [hide abstract]
ABSTRACT: Endothelial progenitor cells (EPC) reportedly differentiate into endothelial cells and participate in angiogenesis, including neovascularization at sites of neoplastic development. Recently, we reported that Flk+/CD31-/CD34- mesenchymal stem cells (MSC) possess the potential of differentiating into both endothelial and hematopoietic cells. We hypothesized that these MSC contribute to tumor angiogenesis. This concept is controversial and this study was undertaken to address this controversy. We show that progeny of human MSC as well as differentiated endothelial cells possess the ability to participate in tumor angiogenesis. When human marrow-derived MSC were injected into tail veins of severe combined immunodeficient (SCID) mice engrafted with human malignant melanoma, human cells incorporated into tumor vessels. Moreover, human-derived endothelial cells were identified in the walls of mouse tumor vessels by immunohistology. We report for the first time that similar results are obtained when mice carrying malignant melanoma are injected with differentiated human endothelial cells. Thus, we demonstrate that both differentiated endothelial cells from tissue peripheral to that of a tumor as well as progeny of human MSC have similar capacities to participate in angiogenesis.Stem Cells and Development 07/2005; 14(3):292-8. · 4.46 Impact Factor -
Article: Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice.
[show abstract] [hide abstract]
ABSTRACT: Fibrosis is the common end stage of most liver diseases, for which, unfortunately, there is no effective treatment available currently. It has been shown that mesenchymal stem cells (MSCs) from bone marrow (BM) could engraft in the lung after bleomycin exposure and ameliorate its fibrotic effects. This study was designed to evaluate the effect of Flk1 MSCs from murine BM (termed here Flk1 mMSCs) on fibrosis formation induced by carbon tetrachloride (CCl4). A CCl(4)-induced hepatic fibrosis model was used. Flk1 mMSCs were systemically infused immediately or 1 week after mice were challenged with CCl(4). Control mice received only saline infusion. Fibrosis index and donor-cell engraftment were assessed 2 or 5 weeks after CCl(4) challenge. We found that Flk1 mMSCs transplantation immediately, but not 1 week after exposure to CCl(4), significantly reduced CCl(4)-induced liver damage and collagen deposition. In addition, levels of hepatic hydroxyproline and serum fibrosis markers in mice receiving immediate Flk1 mMSCs transplantation after CCl(4) challenge were significantly lower compared with those of control mice. More importantly, histologic examination suggested that hepatic damage recovery was much better in these immediately Flk1 mMSCs-treated mice. Immunofluorescence, polymerase chain reaction, and fluorescence in situ hybridization analysis revealed that donor cells engrafted into host liver, had epithelium-like morphology, and expressed albumin, although at low frequency. These results suggest that Flk1 mMSCs might initiate endogenous hepatic tissue regeneration, engraft into host liver in response to CCl(4) injury, and ameliorate its fibrogenic effects.Transplantation 08/2004; 78(1):83-8. · 4.00 Impact Factor -
Article: Multipotency of Flk1CD34 progenitors derived from human fetal bone marrow.
[show abstract] [hide abstract]
ABSTRACT: We report that a cell population derived from human fetal bone marrow, termed Flk1+CD34- multipotent stem cells, can differentiate not only into osteogenic, adipogenic, and endothelial lineages but also into hepatocyte-like cells and neural and erythroid cells at the single-cell level. We depleted mononuclear cells from fetal bone marrow of CD45+, GlyA+, and CD34+ cells with the use of micromagnetic beads, then cultured them by limiting dilution. Three single colonies were harvested, expanded, and characterized. The clones have been expanded for more than 50 cell doublings, and cell-doubling time was about 30 hours. About 90% cells were in the G(0)/G(1) phase of the cell cycle, and the cells from the single colony maintained Flk1+ and CD34-. Because fetal bone marrow-derived Flk1+CD34-multipotent stem cells have the capacity for self-renewal and multilineage differentiation even after being expanded for more than 50 cell doublings, they may be an ideal source of stem cells for the treatment of inherited or degenerative diseases.Journal of Laboratory and Clinical Medicine 05/2004; 143(4):230-40. · 2.62 Impact Factor -
Article: Multiorgan engraftment and multilineage differentiation by human fetal bone marrow Flk1+/CD31-/CD34- Progenitors.
[show abstract] [hide abstract]
ABSTRACT: We previously reported that Flk1(+)/CD31(-)/CD34(-) cells isolated from human fetal bone marrow can differentiate at the single cell level into endothelial and hematopoietic cells in vitro. Here we report that within this cell population reside cells that can differentiate into the epithelium of liver, lung, gut, as well as the cells of both hematopoietic and endothelial system after primary or secondary transplantation into irradiated nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Hence, Flk1(+)/CD31(-)/CD34(-) cells possess remarkable differentiation potential and may thereby provide an alternative to hematopoietic stem cells for transplantation. In addition, our results show this stem cell population effectively accelerated wound healing in NOD/SCID mice and thus holds therapeutic promise for treatment of genetic disorders, organ dysfunction, and tissue repair in humans.Journal of Hematotherapy & Stem Cell Research 01/2004; 12(6):603-13.
Top co-authors
Top Journals
Institutions
-
2004–2012
-
Chinese Academy of Medical Sciences
Beijing, Beijing Shi, China
-
-
2009
-
Kunming Medical College
- Department of Hematology
Kunming, Yunnan, China
-
-
2006–2008
-
Peking Union Medical College Hospital
Beijing, Beijing Shi, China
-
-
2005
-
Tianjin Medical University
Harbin, Heilongjiang Sheng, China
-
