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Mesenchymal cell transplantation lupus

Dandan Wang, Huayong Zhang, Jun Liang, Hong Wang, Bingzhu Hua, Xuebing Feng, Gary S Gilkeson, Dominique Farge, Songtao Shi, Lingyun Sun
Allogeneic mesenchymal stem/stromal cells (MSCs) have been widely studied as an alternative cell source for regenerative medicine. Here, we report a long-term follow-up study of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT) in severe and drug-refractory systemic lupus erythematosus (SLE) patients. Eighty-one patients were enrolled, and the 5-year overall survival rate was 84% (68/81) after MSCT. At 5-year follow-up, 27% of patients (22/81) were in complete clinical remission and another 7% (6/81) were in partial clinical remission, with a 5-year disease remission rate of 34% (28/81)...
March 13, 2018: Stem Cell Reports
Dandan Wang, Shiying Wang, Saisai Huang, Zhuoya Zhang, Xinran Yuan, Xuebing Feng, Liwei Lu, Lingyun Sun
Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) show immunoregulatory properties on various immune cells and display therapeutic effects on various autoimmune diseases such as systemic lupus erythematosus (SLE). The aim of this study was to investigate the effect of the SLE environment on UC MSCs and to identify a potential serum biomarker to predict the therapeutic effect. UC MSCs were cocultured with peripheral blood mononuclear cells (PBMCs) from active lupus patients, and the proliferation, apoptosis and surface markers of UC MSCs were observed...
September 2017: Stem Cells Translational Medicine
Anna Niezgoda, Piotr Niezgoda, Laura Nowowiejska, Agnieszka Białecka, Kaja Męcińska-Jundziłł, Urszula Adamska, Rafał Czajkowski
Stem cells play an important role in medical science, and scientists are investing large sums in order to perform sophisticated studies designed to establish potential clinical applications of stem cells. Growing experience has enabled researchers to determine the precise nature of stem cell division. Although the properties of this particular population of cells have been known and used for some time, mainly with regards to bone marrow-derived mesenchymal stem cell transplantation, we now face a significant challenge in implementing the practical use of skin-derived precursors, making it possible to avoid the necessity for patients to undergo invasive procedures in order to obtain stem cells from bone marrow...
March 11, 2017: European Journal of Dermatology: EJD
Chen Chen, Jun Liang, Genhong Yao, Haifeng Chen, Bingyu Shi, Zhuoya Zhang, Cheng Zhao, Huayong Zhang, Lingyun Sun
BACKGROUND: Soluble human leukocyte antigen-G (sHLA-G) is a non-classical HLA class I molecule, exhibiting strong immunosuppressive properties by inducing the differentiation of T regulatory cells (Treg). Mesenchymal stem cells (MSCs) transplantation alleviates disease progression in systemic lupus erythematosus (SLE) patients. However, the underlying mechanisms are largely unknown. OBJECTIVES: To explore whether sHLA-G is involved in upregulating effects of MSCs on Treg, which contributes to therapeutic effects of MSCs transplantation in SLE...
March 2017: International Immunopharmacology
Zhuoya Zhang, Ruihai Feng, Lingying Niu, Saisai Huang, Wei Deng, Bingyu Shi, Genhong Yao, Weiwei Chen, Xiaojun Tang, Xiang Gao, Xuebing Feng, Lingyun Sun
The aberrant generation or activation of T follicular helper (Tfh) cells contributes to the pathogenesis of systemic lupus erythematosus (SLE), yet little is known about how these cells are regulated. In this study, we demonstrated that the frequency of Tfh cells was increased in lupus-prone B6.MRL-Faslpr (B6.lpr) mice and positively correlated to plasma cell proportions and serum total IgG as well as anti-dsDNA antibody levels. Transplantation of mesenchymal stem cells derived from Wharton's jelly of human umbilical cords (hUC-MSCs) ameliorated lupus symptoms in B6...
June 9, 2017: Cell Transplantation
Eun Wha Choi, MinJae Lee, Ji Woo Song, Il Seob Shin, Sung Joo Kim
C3.MRL-Fas(lpr)/J mice spontaneously develop high titers of anti-dsDNA, mild glomerular nephritis, and severe lymphoproliferation symptoms. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), and cyclophosphamide treatment in C3.MRL-Fas(lpr)/J mice using a murine SLE model. C3.MRL-Fas(lpr)/J mice were divided into saline (C), cyclophosphamide (Y), and ASC (H) treatment groups. Background-matched control C3H mice treated with saline (N) were also compared...
December 7, 2016: Scientific Reports
Anna Julie Peired, Alessandro Sisti, Paola Romagnani
Mesenchymal stem cells form a population of self-renewing, multipotent cells that can be isolated from several tissues. Multiple preclinical studies have demonstrated that the administration of exogenous MSC could prevent renal injury and could promote renal recovery through a series of complex mechanisms, in particular via immunomodulation of the immune system and release of paracrine factors and microvesicles. Due to their therapeutic potentials, MSC are being evaluated as a possible player in treatment of human kidney disease, and an increasing number of clinical trials to assess the safety, feasibility, and efficacy of MSC-based therapy in various kidney diseases have been proposed...
2016: Stem Cells International
Ying-Jie Nie, Li-Mei Luo, Yan Zha, Li Sun, Ji Luo, Run-Sang Pan, Xiao-Bin Tian
OBJECTIVE: To investigate whether plasma from patients with systemic lupus erythematosus (SLE) inhibits the suppressive effects of mesenchymal stem cells (MSCs) on lupus B lymphocytes. METHODS: MSCs isolated and expanded from the bone marrow of healthy donors were co-cultured with B cells purified from the peripheral blood of SLE patients in the presence of fetal bovine serum or pooled plasma from SLE patients, and the proliferation and maturation of the B lymphocytes were analyzed...
August 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Guang-Ping Ruan, Xiang Yao, Ju-Fen Liu, Jie He, Zi-An Li, Jian-Yong Yang, Rong-Qing Pang, Xing-Hua Pan
BACKGROUND: The establishment of a tree shrew model for systemic lupus erythematosus (SLE) provides a new method to evaluate the pathogenesis of autoimmune diseases. METHODS: Eighty tree shrews were randomly divided into four groups receiving either an intraperitoneal injection of pristane, lipopolysaccharide (LPS), or pristane and LPS, or no injection. Three weeks after injection, the SLE model tree shrews were divided into the model group and the treatment group...
August 24, 2016: Stem Cell Research & Therapy
Dandan Wang, Lingying Niu, Xuebing Feng, Xinran Yuan, Shengnan Zhao, Huayong Zhang, Jun Liang, Cheng Zhao, Hong Wang, Bingzhu Hua, Lingyun Sun
The aim of this study is to assess the long-term safety of allogeneic umbilical cord mesenchymal stem cells (UC MSCs) transplantation for patients with refractory systemic lupus erythematosus (SLE). Nine SLE patients, who were refractory to steroid and immunosuppressive drugs treatment and underwent MSCs transplantation in 2009, were enrolled. One million allogeneic UC MSCs per kilogram of body weight were infused intravenously at days 0 and 7. The possible adverse events, including immediately after MSCs infusions, as well as the long-term safety profiles were observed...
August 2017: Clinical and Experimental Medicine
Mi-Young Son, Mi-Ok Lee, Hyejin Jeon, Binna Seol, Jung Hwa Kim, Jae-Suk Chang, Yee Sook Cho
Autoimmune diseases (AIDs), a heterogeneous group of immune-mediated disorders, are a major and growing health problem. Although AIDs are currently treated primarily with anti-inflammatory and immunosuppressive drugs, the use of stem cell transplantation in patients with AIDs is becoming increasingly common. However, stem cell transplantation therapy has limitations, including a shortage of available stem cells and immune rejection of cells from nonautologous sources. Induced pluripotent stem cell (iPSC) technology, which allows the generation of patient-specific pluripotent stem cells, could offer an alternative source for clinical applications of stem cell therapies in AID patients...
May 13, 2016: Experimental & Molecular Medicine
Zhifeng Gu, Wei Tan, Juan Ji, Guijian Feng, Yan Meng, Zhanyun Da, Genkai Guo, Yunfei Xia, Xinhang Zhu, Guixiu Shi, Chun Cheng
We have shown that bone marrow (BM)-derived mesenchymal stem cells (BM-MSCs) from SLE patients exhibit senescent behavior and are involved in the pathogenesis of SLE. The aim of this study was to investigate the effects of rapamycin (RAPA) on the senescences and immunoregulatory ability of MSCs of MRL/lpr mice and SLE patients and the underlying mechanisms. Cell morphology, senescence associated β-galactosidase (SA-β-gal) staining, F-actin staining were used to detect the senescence of cells. BM-MSCs and purified CD4+ T cells were co-cultured indirectly...
May 2016: Aging
Audrey Cras, Dominique Farge, Thierry Carmoi, Jean-Jacques Lataillade, Dan Dan Wang, Lingyun Sun
Current systemic therapies are rarely curative for patients with severe life-threatening forms of autoimmune diseases (ADs). During the past 15 years, autologous hematopoietic stem cell transplantation has been demonstrated to cure some patients with severe AD refractory to all other available therapies. As a consequence, ADs such as lupus and scleroderma have become an emerging indication for cell therapy. Multipotent mesenchymal stem cells (MSCs), isolated from bone marrow and other sites, display specific immunomodulation and anti-inflammatory properties and appear as ideal tools to treat such diseases...
November 3, 2015: Arthritis Research & Therapy
Kelvin S Ng, Thomas M Kuncewicz, Jeffrey M Karp
While mesenchymal stem cells (MSCs) are rapidly cleared from the body following systemic transplantation, their therapeutic benefits typically persist. In this issue, Liu et al. (2015) reveal that the ability of transplanted MSCs to alleviate osteoporosis in systemic lupus erythematosus is maintained through epigenetic changes conferred by secretory action of the MSCs.
October 6, 2015: Cell Metabolism
Dandan Wang, Saisai Huang, Xinran Yuan, Jun Liang, Renju Xu, Genhong Yao, Xuebing Feng, Lingyun Sun
BACKGROUND AND OBJECTIVE: Umbilical cord (UC)-derived mesenchymal stem cells (MSCs) have shown immunoregulation of various immune cells. The aim of this study was to investigate the mechanism of UC MSCs in the regulation of peripheral regulatory T cells (Treg) and T helper 17 (Th17) cells in patients with systemic lupus erythematosus (SLE). METHODS: Thirty patients with active SLE, refractory to conventional therapies, were given UC MSCs infusions. The percentages of peripheral blood CD4+CD25+Foxp3+ regulatory T cells (Treg) and CD3+CD8-IL17A+ Th17 cells and the mean fluorescence intensities (MFI) of Foxp3 and IL-17 were measured at 1 week, 1 month, 3 months, 6 months, and 12 months after MSCs transplantation (MSCT)...
May 2017: Cellular & Molecular Immunology
Eun Wha Choi, Hee Woo Lee, Il Seob Shin, Ji Hyun Park, Tae Won Yun, Hwa Young Youn, Sung-Joo Kim
Allogeneic and xenogeneic transplantation are suitable alternatives for treating patients with stem cell defects and autoimmune diseases. The purpose of this study was to compare the effects of long-term serial transplantation of adipose tissue-derived mesenchymal stem cells (ASCs) from (NZB × NZW) F1 mice (syngeneic), BALB/c mice (allogeneic), or humans (xenogeneic) on systemic lupus erythematosus (SLE). The effects of transplanting human ASCs overproducing CTLA4Ig (CTLA4Ig-hASC) were also compared. Animals were divided into five experimental groups, according to the transplanted cell type...
2016: Cell Transplantation
Shiyu Liu, Dawei Liu, Chider Chen, Kazunori Hamamura, Alireza Moshaverinia, Ruili Yang, Yao Liu, Yan Jin, Songtao Shi
Mesenchymal stem cell transplantation (MSCT) has been used to treat human diseases, but the detailed mechanisms underlying its success are not fully understood. Here we show that MSCT rescues bone marrow MSC (BMMSC) function and ameliorates osteopenia in Fas-deficient-MRL/lpr mice. Mechanistically, we show that Fas deficiency causes failure of miR-29b release, thereby elevating intracellular miR-29b levels, and downregulates DNA methyltransferase 1 (Dnmt1) expression in MRL/lpr BMMSCs. This results in hypomethylation of the Notch1 promoter and activation of Notch signaling, in turn leading to impaired osteogenic differentiation...
October 6, 2015: Cell Metabolism
Wei Deng, Weiwei Chen, Zhuoya Zhang, Saisai Huang, Wei Kong, Yue Sun, Xiaojun Tang, Genhong Yao, Xuebing Feng, WanJun Chen, Lingyun Sun
Human umbilical cord-derived mesenchymal stem cells (UCMSCs) show therapeutic effects on systemic lupus erythematosus (SLE). Deficiency in functional polarization and phagocytosis in macrophages has been suggested in the pathogenesis of SLE. We found that macrophages from B6.MRL-Fas(lpr) mice exhibited lower level of CD206, the marker for alternatively activated macrophage (AAM, also called M2). In addition, the phagocytic activity of B6.MRL-Fas(lpr) macrophages was also decreased. UCMSC transplantation improved the proportion of CD206(+) macrophages and their phagocytic activity in B6...
December 2015: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Dandan Wang, Huayong Zhang, Jun Liang, Xia Li, Xuebing Feng, Hong Wang, Bingzhu Hua, Bujun Liu, Liwei Lu, Gary S Gilkeson, Richard M Silver, Wanjun Chen, Songtao Shi, Lingyun Sun
Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitors and are capable of differentiating into several tissues of mesenchymal origin. We have shown that bone marrow derived MSCs from both SLE patients and lupus prone MRL/lpr mice are defective structurally and functionally. Here we observe the long-term safety and efficacy of allogeneic MSC transplantation (MSCT) in treatment-resistant SLE patients. Eighty-seven patients with persistently active SLE who were refractory to standard treatment or had life-threatening visceral involvement were enrolled...
October 31, 2012: Cell Transplantation
Lan Ma, Reona Aijima, Yoshihiro Hoshino, Haruyoshi Yamaza, Erika Tomoda, Yosuke Tanaka, Soichiro Sonoda, Guangtai Song, Wei Zhao, Kazuaki Nonaka, Songtao Shi, Takayoshi Yamaza
INTRODUCTION: Secondary osteoporosis is common in systemic lupus erythematosus and leads to a reduction in quality of life due to fragility fractures, even in patients with improvement of the primary disorder. Systemic transplantation of mesenchymal stem cells could ameliorate bone loss and autoimmune disorders in a MRL/lpr mouse systemic lupus erythematosus model, but the detailed therapeutic mechanism of bone regeneration is not fully understood. In this study, we transplanted human bone marrow mesenchymal stem cells (BMMSCs) and stem cells from exfoliated deciduous teeth (SHED) into MRL/lpr mice and explored their therapeutic mechanisms in secondary osteoporotic disorders of the systemic lupus erythematosus model mice...
May 27, 2015: Stem Cell Research & Therapy
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