Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management

2022 ◽  
pp. 101524
Author(s):  
Reza Mirfakhraie ◽  
Maria Tavakoli Ardakani ◽  
Abbas Hajifathali ◽  
Samira Karami ◽  
Mohammad Reza Moshari ◽  
...  
2011 ◽  
Vol 9 (2) ◽  
pp. 224-228 ◽  
Author(s):  
Luciana Cavalheiro Marti ◽  
Andreza Alice Feitosa Ribeiro ◽  
Nelson Hamerschlak

Mesenchymal stem cells represent an adult population of nonhematopoietic cells, which can differentiate into a variety of cell types such as osteocytes, chondrocytes, adipocytes, and myocytes. They display immunomodulatory properties that have led to the consideration of their use for the inhibition of immune responses. In this context, mesenchymal stem cells efficiently inhibit maturation, cytokine production, and the T cell stimulatory capacity of dendritic cells. They also can impair proliferation, cytokine secretion, and cytotoxic potential of T lymphocytes. Moreover, mesenchymal stem cells are able to inhibit the differentiation of B cells to plasma cells by inhibiting their capacity to produce antibodies. A variety of animal models confirm the immunomodulatory properties of mesenchymal stem cells. Clinical studies including patients with severe acute graft-versus-host disease have revealed that the administration of mesenchymal stem cells results in significant clinical responses. Therefore, mesenchymal stem cells improve acute graft-versus-host disease and represent a promising candidate for the prevention and treatment of immune-mediated diseases, due to their immunomodulatory capability and their low immunogenicity.


The Lancet ◽  
2004 ◽  
Vol 363 (9419) ◽  
pp. 1439-1441 ◽  
Author(s):  
Katarina Le Blanc ◽  
Ida Rasmusson ◽  
Berit Sundberg ◽  
Cecilia Götherström ◽  
Moustapha Hassan ◽  
...  

Author(s):  
Masayuki Fujino ◽  
Ping Zhu ◽  
Yusuke Kitazawa ◽  
Ji-Mei Chen ◽  
Jian Zhuang ◽  
...  

2020 ◽  
Vol 6 (16) ◽  
pp. eaba1334 ◽  
Author(s):  
Jisun Lim ◽  
Jinbeom Heo ◽  
Hyein Ju ◽  
Ji-Woong Shin ◽  
YongHwan Kim ◽  
...  

Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling. MSCs with enhanced GSH levels and GRC mediated by CREB1-NRF2 have improved self-renewal, migratory, anti-inflammatory, and T cell suppression capacities. Administration of MSCs overexpressing CREB1-NRF2 target genes alleviated GVHD in a humanized mouse model, resulting in improved survival, decreased weight loss, and reduced histopathologic damages in GVHD target organs. Collectively, these findings demonstrate the molecular and functional importance of the CREB1-NRF2 pathway in maintaining MSC GSH dynamics, determining therapeutic outcomes for GVHD treatment.


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