Adipose‐derived mesenchymal stem cells modulate the immune response in chronic experimental autoimmune encephalomyelitis model

Abstract

Multiple sclerosis (MS) is an autoimmune inflammatory neurodegenerative disease of the central nervous system (CNS) that disrupts the myelin sheath, leading to dysfunction of the brain and spinal cord. No curative treatment is known for MS. Mesenchymal stem cells, through their immunomodulatory effects, represent a promising therapeutic approach for MS. The aim of this article is to explore the impact of human adiposederived mesenchymal stem cells (ASCs) on chronic experimental autoimmune encephalomyelitis (EAE) model of MS when injected after a disease entered an irreversible clinical course. Forty-one female albino rats were classified into the following groups: I: control, II: EAE-untreated, III and IV: EAE treated with PBS at 15 and 25 days postimmunization (dpi), respectively, V and VI: EAE treated with ASCs at 15 and 25 dpi, respectively. Intravenous administration of ASCs at 15 or 25 dpi significantly ameliorates the disease course and decreases the immune cell infiltration, vascular congestion and axonal loss of the gray and white matters of cerebral cortex. ASCs treatment induced a Th2 shift of the immune response and downregulation of IL-17 levels. We also found an engraftment of the ASCs into the lymph nodes and the brains up to 25 days after injection. The important finding was that human HLA-G gene was significantly expressed in lymph nodes and brains of rats treated with ASCs. Transplantation of human ASCs has demonstrated striking therapeutic effects and unique immunomodulatory capacities when delivered at the peak or later in the course of the disease in EAE rats. Interestingly, ASCs injection at the peak of EAE had better effects Conflict of interest: Nothing to report.

Concise Review: Mesenchymal Stem Cells in Neurodegenerative Diseases

“…Using hBM‐MSCs, Bai et al showed a decrease in leukocyte infiltration into the CNS and enhanced a Th2 cytokine profile, but also enhanced oligodendrogenesis, suggesting that hBM‐MSCs affect immunomodulation but also enhanced neuronal repair . Similar results showing a Th2 cytokine shift and enhanced oligodendrogenesis were reported using hA‐MSCs and using human decidua‐derived MSCs (hD‐MSCs) . hA‐MSCs were also shown to express the immunosuppressive gene human leukocyte antigen G (HLA‐G) and to induce the secretion of the anti‐inflammatory protein TNF‐α‐stimulated gene/protein 6 following culture with inflammatory cytokines .…”

“…Similar results showing a Th2 cytokine shift and enhanced oligodendrogenesis were reported using hA‐MSCs and using human decidua‐derived MSCs (hD‐MSCs) . hA‐MSCs were also shown to express the immunosuppressive gene human leukocyte antigen G (HLA‐G) and to induce the secretion of the anti‐inflammatory protein TNF‐α‐stimulated gene/protein 6 following culture with inflammatory cytokines . Payne et al tested the effect of hA‐MSCs ex vivo modified to over‐express the anti‐inflammatory ILs‐4 and −10 in EAE mice.…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Therefore, it seems that although AD-MSCs are cultured and expanded in vitro under standard condition, the donor's status could influence their properties by altering inflammatory profile. Shalaby et al (2016) established that the transplantation of human AD-MSCs taken from lipoaspirate from the subcutaneous white adipose tissue of healthy donors had beneficial effects on chronic EAE rats. In detail, AD-MSCs (1 × 10 6 ) injected intravenously improved clinical disease score and reduced B-cell, macrophage, and T-cell infiltration in brain, as well as vascular congestion and axonal loss of the gray and white matters of cerebral cortex.…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…Brains and lymph nodes of EAE rats treated with AdMSCs show a significant expression of human leukocyte antigen G (HLA-G) gene. The immunomodulatory effects of AdMSCs may be related to their secretion of HLA-G (73). Engineering of AdMSCs as carriers for IFN-β delivery, or secretors of IL-10, has shown beneficial effects in experimental models of MS (74,75).…”