Yujie Wen - Academia.edu (original) (raw)
Papers by Yujie Wen
Transplantation, 2011
Background-FoxP3 + /CD4 + /CD25 + regulatory T cells (T reg) play an important role in maintainin... more Background-FoxP3 + /CD4 + /CD25 + regulatory T cells (T reg) play an important role in maintaining peripheral tolerance and are potent suppressors of T cell activation. In the present studies we evaluated the role T reg might play in peripheral tolerance to composite tissue allotransplants (CTA). Methods-Mixed allogeneic chimeric rats were prepared by pre-conditioning recipients with anti-αβ-TCR monoclonal antibody (mAb) followed by total body irradiation. Animals received T cell-depleted ACI bone marrow cells followed by anti-lymphocyte serum and FK-506. A modified osteomyocutaneous hind-limb flap composed of bone and all limb tissue components was placed at 29 days in animals with chimerism ≥ 1% on day 28. Recipients with CTA surviving ≥ 6 months were evaluated for T reg. Skin from tolerant long-term allogeneic transplanted, syngeneic transplanted, rejected and naïve animals were immunostained with fluorochrome conjugated anti-FoxP3 and anti-CD4 mAb and visualized under a laser confocal microscope. Results-Significant CD4 + /FoxP3 + T reg infiltrates were observed in tolerant donor-allograft skin samples. No graft infiltrating FoxP3 + cells were observed in rejector, naïve, or syngeneic CTA transplanted skin. In parallel experiments, mixed leukocyte reactions assays were performed to investigate the suppressor function of T reg cells. Splenocytes from tolerant, rejected, and naïve rats were sorted by flow cytometry for CD4 + /CD25 + T cells. T reg demonstrated similar suppressive levels between the three groups.
OBM Transplantation, 2018
This review summarizes the latest results from the interventional clinical trials for inducing cl... more This review summarizes the latest results from the interventional clinical trials for inducing clinical tolerance in the recipients of human leukocyte antigen (HLA)-matched or mismatched living donor kidney transplants via allogeneic hematopoietic stem cell (HSC)based therapies. The protocols utilized by the three medical centers in the United States differ in degree of HLA-matching, relatedness or unrelatedness, donor cell composition of the hematopoietic stem cells transplant (HSCT), timing for infusion and conditioning regimens. Tolerant recipients from the clinical trials benefited from better long-term outcome, improved quality of life and reduction in lifetime healthcare expenses compared with standard-of-care recipients on conventional immunosuppression. Durable chimerism induced by concomitant HSCT is indispensable to achieve immunologic tolerance to kidney transplantation and to protect against recurrence of the original renal disease in HLAmismatched related and unrelated kidney transplant recipients.
Stem Cells, 2014
CD8+TCR− graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in... more CD8+TCR− graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function. DOCK2−/− FCs exhibit compromised facilitative function in vivo as evidenced by the loss of engraftment-enhancing capability for c-Kit+Sca-1+lineage− (KSL) cells, and compromised ability to promote KSL cell homing and lodgment in hematopoietic niche. Deletion of DOCK2 abrogates the ability of FCs to induce differentiation of naïve CD4+CD25− T cells into FoxP3+ regulatory T cells and interleukin-10-producing type 1 regulatory T cells in vitro. Moreover, DOCK2−/− FCs are unable to promote survival of KSL cells when cocultured with KSL cells. DOCK2−/− FCs also exhibit compromised migration to stroma-derived factor-1 in vitro ...
Expert Opinion on Biological Therapy, 2011
Importance of the field-Beta cell regeneration and beta cell preservation are two promising thera... more Importance of the field-Beta cell regeneration and beta cell preservation are two promising therapeutic approaches for the management of patients with Type 1 diabetes (T1D). Stem cellbased strategies to address the problems of shortage in beta cells, autoimmune and alloimmune responses have become an area of intense study. Areas covered in this review-This review focuses on the progress that has been made in obtaining functional, insulin-producing cells from various types of stem/progenitor cells, including the current knowledge on the immunomodulatory roles of hematopoietic stem cell and multipotent stromal cell in the therapies for T1D. What the reader will gain-A broad overview of recent advancements in this field is provided. The hurdles that remain in the path of using stem cell-based strategies for the treatment of T1D and possible approaches to overcome these challenges are discussed. Take home message-Stem cell-based strategies hold great promise for the treatment of T1D. In spite of the progress that has been made over the last decade, a number of obstacles and concerns need to be cleared before widespread clinical application is possible. In particular, the mechanism of ESC and iPSC-derived beta cell maturation in vivo is poorly understood.
Nephron …, 2006
Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is... more Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial ...
Translational Research, 2008
Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by a... more Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by aristolochic acid intake. To determine the contribution of renal ischemia to the pathogenesis of AAN, we characterized changes in the expression of angiogenic factors and vasoactive substances, and then we evaluated the expression of a marker of hypoxia in an acute AAN rat model. Rats were orally administrated either a decoction of Aristolochiae manshuriensis that contained 20 mg/kg of aristolochic acid-I or an equal volume of distilled water (control group) once daily for 4 days or 7 days. Renal histology and serum creatinine were assessed. Expression of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1alpha) mRNA within renal cortex were determined by semiquantitative reverse-transcription polymerase chain reaction. Levels of ET-1, nitric oxide (NO), vascular endothelial growth factor (VEGF), and HIF-1alpha in kidneys were determined by radioimmunoassay, Griess method, Western blot, and immunohistochemistry, respectively. Tubular injury scores and ET-1 mRNA expression were increased in the AA-treated rats at both days 4 and 8, whereas serum creatinine level and ET-1 protein expression was increased only at day 4. In contrast, NO production in AA-treated rats was decreased at day 8 compared with the control group. Similarly, VEGF protein expression was reduced in the AA-treated rats at both days 4 and 8. A dramatic increase in nuclear staining for HIF-1alpha was observed mainly in the tubular cells of tubulointerstitial damage area in the AA-treated rats at day 8. The observed increase in HIF-1alpha protein expression, decrease in VEGF protein expression, and imbalance of vasoactive substances after induction of acute kidney injury by AA suggests that ischemic injury contributes to the pathogenesis of AAN.
Transplantation, 2011
Background-FoxP3 + /CD4 + /CD25 + regulatory T cells (T reg) play an important role in maintainin... more Background-FoxP3 + /CD4 + /CD25 + regulatory T cells (T reg) play an important role in maintaining peripheral tolerance and are potent suppressors of T cell activation. In the present studies we evaluated the role T reg might play in peripheral tolerance to composite tissue allotransplants (CTA). Methods-Mixed allogeneic chimeric rats were prepared by pre-conditioning recipients with anti-αβ-TCR monoclonal antibody (mAb) followed by total body irradiation. Animals received T cell-depleted ACI bone marrow cells followed by anti-lymphocyte serum and FK-506. A modified osteomyocutaneous hind-limb flap composed of bone and all limb tissue components was placed at 29 days in animals with chimerism ≥ 1% on day 28. Recipients with CTA surviving ≥ 6 months were evaluated for T reg. Skin from tolerant long-term allogeneic transplanted, syngeneic transplanted, rejected and naïve animals were immunostained with fluorochrome conjugated anti-FoxP3 and anti-CD4 mAb and visualized under a laser confocal microscope. Results-Significant CD4 + /FoxP3 + T reg infiltrates were observed in tolerant donor-allograft skin samples. No graft infiltrating FoxP3 + cells were observed in rejector, naïve, or syngeneic CTA transplanted skin. In parallel experiments, mixed leukocyte reactions assays were performed to investigate the suppressor function of T reg cells. Splenocytes from tolerant, rejected, and naïve rats were sorted by flow cytometry for CD4 + /CD25 + T cells. T reg demonstrated similar suppressive levels between the three groups.
OBM Transplantation, 2018
This review summarizes the latest results from the interventional clinical trials for inducing cl... more This review summarizes the latest results from the interventional clinical trials for inducing clinical tolerance in the recipients of human leukocyte antigen (HLA)-matched or mismatched living donor kidney transplants via allogeneic hematopoietic stem cell (HSC)based therapies. The protocols utilized by the three medical centers in the United States differ in degree of HLA-matching, relatedness or unrelatedness, donor cell composition of the hematopoietic stem cells transplant (HSCT), timing for infusion and conditioning regimens. Tolerant recipients from the clinical trials benefited from better long-term outcome, improved quality of life and reduction in lifetime healthcare expenses compared with standard-of-care recipients on conventional immunosuppression. Durable chimerism induced by concomitant HSCT is indispensable to achieve immunologic tolerance to kidney transplantation and to protect against recurrence of the original renal disease in HLAmismatched related and unrelated kidney transplant recipients.
Stem Cells, 2014
CD8+TCR− graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in... more CD8+TCR− graft facilitating cells (FCs) enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic and syngeneic recipients. The mechanisms by which FCs promote HSC engraftment and tolerance induction have not been fully elucidated. Here, we provide data to support a critical role for dedicator of cytokinesis 2 (DOCK2) in multiple aspects of FCs function. DOCK2−/− FCs exhibit compromised facilitative function in vivo as evidenced by the loss of engraftment-enhancing capability for c-Kit+Sca-1+lineage− (KSL) cells, and compromised ability to promote KSL cell homing and lodgment in hematopoietic niche. Deletion of DOCK2 abrogates the ability of FCs to induce differentiation of naïve CD4+CD25− T cells into FoxP3+ regulatory T cells and interleukin-10-producing type 1 regulatory T cells in vitro. Moreover, DOCK2−/− FCs are unable to promote survival of KSL cells when cocultured with KSL cells. DOCK2−/− FCs also exhibit compromised migration to stroma-derived factor-1 in vitro ...
Expert Opinion on Biological Therapy, 2011
Importance of the field-Beta cell regeneration and beta cell preservation are two promising thera... more Importance of the field-Beta cell regeneration and beta cell preservation are two promising therapeutic approaches for the management of patients with Type 1 diabetes (T1D). Stem cellbased strategies to address the problems of shortage in beta cells, autoimmune and alloimmune responses have become an area of intense study. Areas covered in this review-This review focuses on the progress that has been made in obtaining functional, insulin-producing cells from various types of stem/progenitor cells, including the current knowledge on the immunomodulatory roles of hematopoietic stem cell and multipotent stromal cell in the therapies for T1D. What the reader will gain-A broad overview of recent advancements in this field is provided. The hurdles that remain in the path of using stem cell-based strategies for the treatment of T1D and possible approaches to overcome these challenges are discussed. Take home message-Stem cell-based strategies hold great promise for the treatment of T1D. In spite of the progress that has been made over the last decade, a number of obstacles and concerns need to be cleared before widespread clinical application is possible. In particular, the mechanism of ESC and iPSC-derived beta cell maturation in vivo is poorly understood.
Nephron …, 2006
Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is... more Background/Aims:Aristolochic acid nephropathy, a progressive tubulointerstitial renal disease, is predominantly a result of aristolochic acid I (AA-I) intoxication. However, other unidentified phytotoxins have indeed been postulated as the cause of this unique interstitial ...
Translational Research, 2008
Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by a... more Aristolochic acid nephropathy (AAN) is a progressive tubulointerstitial renal disease caused by aristolochic acid intake. To determine the contribution of renal ischemia to the pathogenesis of AAN, we characterized changes in the expression of angiogenic factors and vasoactive substances, and then we evaluated the expression of a marker of hypoxia in an acute AAN rat model. Rats were orally administrated either a decoction of Aristolochiae manshuriensis that contained 20 mg/kg of aristolochic acid-I or an equal volume of distilled water (control group) once daily for 4 days or 7 days. Renal histology and serum creatinine were assessed. Expression of endothelin-1 (ET-1) and hypoxia inducible factor-1 alpha (HIF-1alpha) mRNA within renal cortex were determined by semiquantitative reverse-transcription polymerase chain reaction. Levels of ET-1, nitric oxide (NO), vascular endothelial growth factor (VEGF), and HIF-1alpha in kidneys were determined by radioimmunoassay, Griess method, Western blot, and immunohistochemistry, respectively. Tubular injury scores and ET-1 mRNA expression were increased in the AA-treated rats at both days 4 and 8, whereas serum creatinine level and ET-1 protein expression was increased only at day 4. In contrast, NO production in AA-treated rats was decreased at day 8 compared with the control group. Similarly, VEGF protein expression was reduced in the AA-treated rats at both days 4 and 8. A dramatic increase in nuclear staining for HIF-1alpha was observed mainly in the tubular cells of tubulointerstitial damage area in the AA-treated rats at day 8. The observed increase in HIF-1alpha protein expression, decrease in VEGF protein expression, and imbalance of vasoactive substances after induction of acute kidney injury by AA suggests that ischemic injury contributes to the pathogenesis of AAN.