scholarly journals The Mechanistic Effects and Clinical Applications of Various Derived Mesenchymal Stem Cells in Immune Thrombocytopenia

2021 ◽  
pp. 1-9
Author(s):  
Yue He ◽  
Dexiang Ji ◽  
Wei Lu ◽  
Guoan Chen
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Thrombocytopenia ◽  
Autoimmune Disorder ◽  
Immune Dysfunction ◽  
Clinical Applications ◽  
Hematopoietic Stem ◽  
Marrow Mesenchymal Stem Cells ◽  
Underlying Mechanisms ◽  
Functional Defects

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by persistent thrombocytopenia resulting from increased platelet destruction and a loss of autoimmune tolerance. The pathogenesis of ITP is highly complex. Although ITP may be effectively controlled with currently available medications in some patients, a subset of cases remain refractory. The application of mesenchymal stem cells (MSCs) for human hematopoietic stem cell transplantation has increasingly demonstrated that MSCs modulate innate or adaptive immunity, thus resulting in a tolerant microenvironment. Functional defects and immunomodulatory disorders have been observed after the use of bone marrow mesenchymal stem cells (BM-MSCs) from patients with ITP. Here, we summarize the underlying mechanisms and clinical applications of various derived MSCs for ITP treatment, focusing on the main mechanisms underlying the functional defects and immune dysfunction of BM-MSCs from patients with ITP. Functional effects associated with the activation of the p53 pathway include decreased activity of the phosphatidylinositol 3 kinase/Akt pathway and activation of the TNFAIP3/NF-κB/SMAD7 pathway. Immune dysfunction appears to be associated with an impaired ability of BM-MSCs to induce various types of immune cells in ITP. At present, research focusing on MSCs in ITP remains in preliminary stages. The application of autologous or exogenous MSCs in the clinical treatment of ITP has been attempted in only a small case study and must be validated in larger-scale clinical trials.

Progress on the Clinical Applications of Stem Cells for Premature Ovarian Failure

Nano LIFE ◽  
2018 ◽  
Vol 08 (04) ◽  
pp. 1841003
Author(s):  
Wanli Yang ◽  
Yiwei Wang ◽  
Wenqi Shan ◽  
Yingying Gao ◽  
Binbin Ma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Clinical Applications ◽  
Ovarian Failure ◽  
Marrow Mesenchymal Stem Cells ◽  
Stem Cells Transplantation ◽  
Ovarian Structure ◽  
Underlying Mechanisms

Premature ovarian failure (POF) is a heterogeneous disorder characterized by amenorrhea, infertility, lack of estrogen, and elevated gonadotropin levels before the age of 40. Most POF females have fertility problems due to defects of germ cell development or complete ovarian failure. Though hormonal therapy could partially restore ovarian function, effects of these treatments are transient, much less for regeneration and repair of the ovaries. With the rise of regenerative medicine, stem cells transplantation gives new hope for repairing POF related ovaries damage. Studies from animal models indicate that stem cell transplantation can, at least in part, repair ovarian structure, improve ovarian function and fertility in POF, i.e., the bone marrow mesenchymal stem cells (BMSCs) and umbilical cord mesenchymal stem cells (UC-MSCs) can differentiate to ovaries and facilitate fertility recovery. However, the underlying mechanisms remain unclear, which limits their clinical applications. Here, we discuss the recent progress on the clinical applications of stem cells for POF treatment, which would become promising therapies for POF patients.

scholarly journals TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin

Open Biology ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 150258 ◽  
Author(s):  
Nan Wang ◽  
Zubin Zhou ◽  
Tianyi Wu ◽  
Wei Liu ◽  
Peipei Yin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Cells ◽  
Bone Diseases ◽  
Cytokine Activation ◽  
Tnf Α ◽  
Marrow Mesenchymal Stem Cells ◽  
Underlying Mechanisms

Although systemic or local inflammation, commonly featured by cytokine activation, is implicated in patients with bone loss, the underlying mechanisms are still elusive. As microRNAs (miR), a class of small non-coding RNAs involved in essential physiological processes, have been found in bone cells, we aimed to investigate the role of miR for modulating osteogenesis in inflammatory milieu using human bone marrow mesenchymal stem cells (hBM-MSCs). Induced by proinflammatory cytokine TNF-α, miR-150-3p was identified as a key player in suppressing osteogenic differentiation through downregulating β-catenin, a transcriptional co-activator promoting bone formation. TNF-α treatment increased the levels of miR-150-3p, which directly targeted the 3′-UTR of β-catenin mRNA and in turn repressed its expression. In addition, we observed that miR-150-3p expression was increased by TNF-α via IKK-dependent NF-κB signalling. There are three putative NF-κB binding sites in the promoter region of miR-150, and we identified −686 region as the major NF-κB binding site for stimulation of miR-150 expression by TNF-α. Finally, the osteogenic differentiation of hBM-MSCs was inhibited by either miR-150-3p overexpression or TNF-α treatment, which was prevented by anti-miR-150-3p oligonucleotides. Taken together, our data suggested that miR-150-3p integrated inflammation signalling and osteogenic differentiation and may contribute to the inhibition effects of inflammation on bone formation, thus expanding the pathophysiological functions of microRNAs in bone diseases.

Transplantation of Haplo-Identical Bone Marrow-Derived Mesenchymal Stem Cells Together with Hematopoietic Stem Cells To Promote Engraftment in Children. A Phase I/II Multicenter Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2911-2911
Author(s):  
Lynne Margaret van Velzen-Ball ◽  
Katarina Le Blanc ◽  
Arjen C. Lankester ◽  
Helene Roelofs ◽  
Maarten Egeler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Calf Serum ◽  
Donor Cell ◽  
Patient Characteristics ◽  
Allogeneic Transplantation ◽  
Immune Recovery ◽  
Hematopoietic Stem ◽  
Marrow Mesenchymal Stem Cells

Abstract Graft failure or rejection is an identified problem in haplo-identical or second attempt transplantation. In the bone marrow, mesenchymal stem cells (MSCs) have been identified and shown in animal models to enhance hematopoietic stem cell (HSC) engraftment. Advances in techniques and higher quality culture components have allowed the development of an MSC expansion procedure resulting in sufficient MSCs for clinical application. Adult studies have suggested that co-transplantation of MSCs and HSCs in the HLA-identical setting, is feasible and safe. Here we present the first combined clinical experience within the EBMT MSC expansion consortium with respect to co-transplantation of haplo-identical MSCs in the pediatric allogeneic transplantation setting. Six weeks before the SCT, 50 cc of bone marrow are sampled under sterile conditions. Density gradient-separated MNCs are plated into tissue culture flasks in low-glucose DMEM supplemented with 10% fetal calf serum and incubated at 370C with 5% CO2. At 70% confluence, the cells are trypsinized and re-plated at 4x103 cells/ cm2 until the target dose of 1–2 x106/kg recipient body weight is obtained. Enrichment and expansion of MSCs is performed under GMP conditions in nationally accredited laboratories. MSCs (either fresh or cryopreserved) are administered i.v. 4 hours before infusion of donor HSCs. To date 4 children have undergone co-transplantation. Patient characteristics are summarized in the table. All toxicities associated with the procedure were documented, as were the engraftment kinetics and immune recovery. The study was carried out with approval of the respective local ethical committees. The data indicate that expansion and co-transplantation of MSCs is feasible and well tolerated. While the study is ongoing initial engraftment and immune recovery data (compared to historical data) is encouraging and to date there have been no episodes of graft rejection or severe adverse events related to this treatment. Patient characteristics Patient demographics HSC characteristics MSC characteristics UPN Gender Age Diagnosis Donor CD34 dose (106/kg) Donor Cell dose (106/kg) 1 M 15 ANLL mother-haplo 16 mother 1.5 2 M 2 XLPD father-haplo 20 father 1.9 3 M 2 XLPD father-haplo 18.7 father 1.56 4 M 8 SAA URD (2 loci mismatched) 2.65 mother 1.0

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