Abstract 292: Hypoxia Induced Formation of Immunoproteasome Instigates Rejection of Allogeneic Mesenchymal Stem Cells in the Ischemic Heart

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Ejlal Abu-El-Rub ◽  
Weiang Yan ◽  
Niketa Sareen ◽  
Keshav N Alagarsamy ◽  
Alireza Rafieerad ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Leukocyte ◽  
Cardiac Repair ◽  
26S Proteasome ◽  
Ischemic Heart ◽  
Host Immune System ◽  
Poor Survival ◽  
Allogeneic Mscs ◽  
Leukocyte Antigen

Bone marrow derived allogeneic (donor derived) mesenchymal stem cells (MSCs) are considered to be prominent cell type for cardiac repair following a damage due to ischemic heart disease. Even though the outcome of initial allogeneic MSCs based clinical trials was encouraging, the overall enthusiasm lately has declined due to poor survival of transplanted cells in the ischemic heart. We reported in a rat model of myocardial infarction that allogeneic-MSCs became immunogenic after 5 weeks of transplantation and were rejected by host immune system that led to poor survival of implanted cells. The immunoprivilege of MSCs is preserved by absence of cell surface antigen, human leukocyte antigen (HLA) - DRα. We found that in normoxic MSCs, 26S proteasome degrades HLA-DRα and maintains immunoprivilege of MSCs. The exposure to hypoxia leads to inactivation of 26S proteasome and formation of immunoproteasome in MSCs, which is associated with upregulation and activation of HLA-DRα, and as a result MSCs become immunogenic. Furthermore, inhibition of immunoproteasome formation in hypoxic MSCs preserves the immunoprivilege. Therefore, hypoxia induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of allogeneic MSCs and rejection. In our ongoing studies we are investigating if preventing the formation of immunoproteasome would prevent rejection of allogeneic MSCs in the ischemic heart and improve survival of transplanted cells. The outcome of these studies may provide molecular targets to plan interventions to preserve immunoprivilege of allogeneic MSCs in the ischemic heart and improve benefits of allogeneic MSCs for cardiac repair.

scholarly journals Concise review: Combining human leukocyte antigen G and mesenchymal stem cells for immunosuppressant biotherapy

Stem Cells ◽  
2013 ◽  
Vol 31 (11) ◽  
pp. 2296-2303 ◽  
Author(s):  
Abderrahim Naji ◽  
Nathalie Rouas-Freiss ◽  
Antoine Durrbach ◽  
Edgardo D. Carosella ◽  
Luc Sensébé ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Concise Review ◽  
Human Leukocyte Antigen G

scholarly journals Application of mesenchymal stem cell sheet to treatment of ischemic heart disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dehua Chang ◽  
Taibing Fan ◽  
Shuang Gao ◽  
Yongqiang Jin ◽  
Mingkui Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Ventricular Remodeling ◽  
Cell Sheet ◽  
Human Leukocyte ◽  
Heart Tissue ◽  
Ischemic Heart ◽  
Paracrine Effects

AbstractIn recent years, mesenchymal stem cells (MSCs) have been used to improve cardiac function and attenuate adverse ventricular remodeling of the ischemic myocardium through paracrine effects and immunoregulation functions. In combination with cell sheet technology, MSCs could be more easily transplanted to the ischemic area. The long-term retention of MSCs in the affected area was realized and significantly improved the curative effect. In this review, we summarized the research and the applications of MSC sheets to the treatment of ischemic heart tissue. At present, many types of MSCs have been considered as multipotent cells in the treatment of heart failure, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived mesenchymal stem cells (AD-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), and skeletal myoblasts (SMs). Since UC-MSCs have few human leukocyte antigen-II and major histocompatibility complex class I molecules, and are easy to isolate and culture, UC-MSC sheets have been proposed as a candidate for clinical applications to ischemic heart disease.

scholarly journals The Importance of HLA Assessment in “Off-the-Shelf” Allogeneic Mesenchymal Stem Cells Based-Therapies

2019 ◽  
Vol 20 (22) ◽  
pp. 5680 ◽  
Author(s):  
Marta Kot ◽  
Monika Baj-Krzyworzeka ◽  
Rafał Szatanek ◽  
Aleksandra Musiał-Wysocka ◽  
Magdalena Suda-Szczurek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cellular Therapy ◽  
Therapeutic Potential ◽  
Human Leukocyte ◽  
Medical Product ◽  
Invasive Treatment ◽  
Allogeneic Mscs ◽  
Leukocyte Antigens ◽  
Ideal Tool

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide “off-the-shelf” cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient’s immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an “off-the-shelf” medical product.

scholarly journals INCREASED POTENCY OF CARDIAC STEM CELLS COMPARED TO BONE MARROW MESENCHYMAL STEM CELLS IN CARDIAC REPAIR

2011 ◽  
Vol 57 (14) ◽  
pp. E1014
Author(s):  
Behzad Nasehi Oskouei ◽  
Guillaume Lamirault ◽  
Chacko Joseph ◽  
Stephanie Landa ◽  
Marc Dauer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cardiac Repair ◽  
Cardiac Stem Cells ◽  
Marrow Mesenchymal Stem Cells

Abstract MP243: Detection Of Mesenchymal Stem Cells In Mobilized Autologous Peripheral Blood Transplantation From Patients With Ischemic Heart Disease

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Hadyanto Lim ◽  
Umar Zein ◽  
Ilham Hariaji
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Peripheral Blood ◽  
Autologous Transplantation ◽  
White Blood Cells ◽  
Significant Rise ◽  
Ischemic Heart ◽  
Post Transplantation

Background: Mesenchymal stem cells (MSCs) improve the cardiac function and remodeling in patients with ischemic heart disease. However, their presence in the circulating peripheral blood and post-transplantation has not been fully elucidated. We aimed to investigate the effects of intravenous transplantation of mobilized autologous peripheral blood on the number of MSCs in patients with ischemic heart disease. Methods: Granulocyte-colony stimulating factor (G-CSF, 5.0 μg/kg/day) was given subcutaneously once a day for five days to 7 patients (4 women and 3 men, aged 54-69 years) with ischemic heart disease. Leukapheresis procedure was started on the day 5 of G-CSF using the Spectra Optia cell separator. Circulating and intravenous transplantation of autologous MSCs after leukapheresis were analyzed by flow cytometry. MSCs were identified on the basis of dual positive cells (CD73 + /CD105 + or CD90 + /CD73 + or CD90 + /CD105 + ) and detected as MSCs if a cluster of at least 10 cells could be found. Results: MSCs in the circulating peripheral blood and after transplantation were detected in 2 (28%) and 6 (85%) patients, respectively. The frequency of intravenous peripheral blood MSCs increased significantly after transplantation (from 32.57 ± 22.76 x10 -4 % to 58.57 ± 28.49 x 10 -4 % , p<0.001). Moreover, there were significant rise in the total white blood cells count (from 10.25 ± 4.86 x 10 3 /μl to 35.81 ± 7.07 x 10 3 /μl, p<0.001) and the levels of CD34 + cells (from 1.17 ± 0.93 cells/μL to 138.30 ± 11.26 cells/μL, p<0.001) after the infusion. Conclusions: The results show that intravenous transplantation of mobilized autologous peripheral blood increases the number of MSCs in patients with ischemic heart disease. Leukapheresis product of peripheral blood MSCs could therefore be a potential source for autologous transplantation in ischemic heart disease.

scholarly journals Successful Treatment of Plaque Psoriasis with Allogeneic Gingival Mesenchymal Stem Cells: A Case Study

2020 ◽  
Vol 2020 ◽  
pp. 1-4 ◽  
Author(s):  
Sebo Gene Wang ◽  
Nicholas C. Hsu ◽  
Sebo Michelle Wang ◽  
Fu Nan Wang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Plaque Psoriasis ◽  
Inflammatory Diseases ◽  
Treatment Options ◽  
Gingival Tissue ◽  
Complete Regression ◽  
Allogeneic Mscs ◽  
Human Gingiva

Plaque psoriasis is the most common type of psoriasis that manifests as red scaly patches with white scales affecting body areas including scalp, elbows, knees, trunk, and buttocks. Although many treatment options are available including novel biologics, no cure is available. Mesenchymal stem cells (MSCs) have been safely used to treat a variety of human diseases. Allogeneic MSCs possess unique characteristics including hypoimmunogenicity, immunomodulatory, and anti-inflammatory properties, and they are currently being explored for potential therapeutic use for many systemic inflammatory diseases. The human gingival tissue is an easily accessible and obtainable source for the isolation of MSCs. MSCs from adult human gingiva are of fetal-like phenotype, multipotent, and easy to isolate and expand in vitro. Herein, we report a case of a 19-year-old man with a 5-year history of severe plaque psoriasis refractory to multiple topical and systemic therapies who was treated with allogeneic human gingival MSCs. Complete regression was achieved after 5 infusions with no adverse reaction occurred. The patient has been followed for three years and has remained disease free.

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