Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis.
Masoumeh RostamiKamran HaidariHossein AminiMajid ShahbaziPublished in: Molecular neurobiology (2022)
We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.
Keyphrases
- mesenchymal stem cells
- multiple sclerosis
- umbilical cord
- cell therapy
- white matter
- bone marrow
- high fat diet induced
- mouse model
- oxidative stress
- induced apoptosis
- randomized controlled trial
- systematic review
- cell free
- cell proliferation
- peripheral blood
- stem cells
- adipose tissue
- high glucose
- endoplasmic reticulum stress
- drug delivery
- skeletal muscle
- stress induced