Table 7.
List of in vivo studies in which the therapeutic potential of the administration of hMSCs for the treatment of autoimmune neurologic disorders was evaluated.
| References | Autoimmune disease | Source of hMSC | Variables | Experimental model | Clinical and laboratory effects | Mechanism proposed |
|---|---|---|---|---|---|---|
| (102) | Multiple sclerosis | Embryonic stem cells Bone marrow | None | Mice | ↓Clinical score ↓Disease incidence ↑Motor functions Effectiveness embryonic stem cells-derived MSCs > effectiveness bone marrow-derived MSCs |
↓IFN-γ+CD4+ Th1 cells into the central nervous system ↓IL-17+CD4+ Th17 cells into the central nervous system ↓T lymphocyte proliferation ↓B lymphocyte proliferation ↑PD-L1 expression |
| (121) | Multiple sclerosis | Adipose tissue | Administration of MSCs from older donors | Mice | None | |
| Administration of MSCs from younger donors | ↓Clinical score ↑Activity and utilization of the arena space ↑Distance traveled ↑Moving velocity ↑Myelin levels Effectiveness MSCs from younger donors > effectiveness MSCs from older donors |
↓Infiltrating cells in the spinal cord ↓Splenocyte proliferation ↑IL-17 in the serum ↑IL-12 in the serum ↑IFN-γ in the serum |
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| (122) | Multiple sclerosis | Bone marrow | None | Mice | ↓Clinical score ↓Disease progression |
↑Oligodendrocyte lineage cells in lesion areas ↓IFN-γ+CD4+ Th1 cells ↓IL-17+CD4+ Th17 cells ↑IL-4+Th2 cells ↓Infiltrating cells in the central nervous system ↓Extent of the chronic demyelinated regions ↑Oligodendrogenesis ↓Astrogliosis ↓Myelin-specific memory splenocytes ↓IFN-γ ↓TNF-α ↓IL-17 ↓IL-2 ↓IL-12 ↑IL-4 ↑IL-5 |
| (154) | Multiple sclerosis | Bone marrow | None | Mice | ↓Clinical scores ↓Demyelination in the spinal cord |
↓Infiltration of inflammatory cells ↓IL-6 in the serum ↓TNF-α in the serum ↓IL-17 in the serum ↓Splenic cell production and secretion of IL-6, TNF-α and IL-17 ↑Splenic production of IL-10 ↓Splenic Th17 cells ↑CD19+CD5+CD1dhigh Breg cells |
| (123) | Multiple sclerosis | Bone marrow | None | Mice | ↓Disease progression ↑Survival rates ↑Motor function |
↓Spleen cells proliferation |
| (124) | Multiple sclerosis | Umbilical cord stroma | None | Mice | ↓Histopathologic scores ↓Clinical score ↓Demyelination in the spinal cord ↓Axonal injury in the spinal cord |
↓Perivascular immune cell infiltration ↓IL-17+CD4+ Th17 cells ↓IFN-γ/IL-4 ratio ↑CD4+CD25+FOXP3+ Treg cells ↑IL-4 ↑IL-10 ↓IL-17 ↓TNF-α ↓IL-1 in the spinal cord ↓IL-6 in the spinal cord |
| (126) | Multiple sclerosis | Bone marrow | None | Mice | ↓Average clinical score ↓Maximum clinical score ↓Demyelination of the spinal cord |
↓Inflammatory cell infiltration into the central nervous system ↓Inflammatory mononuclear cell infiltration in the white matter of the spinal cord ↓CD4+ cells in the spinal cord ↓Activation of glial cells ↓IFN-γ in the serum ↓TNF-α in the serum ↑IL-4 in the serum ↑IL-10 in the serum ↓MMP-2 activity in the spinal cord ↓MMP-9 activity in the spinal cord |
| (127) | Multiple sclerosis | Bone marrow | None | Mice | None | None |
| (128) | Multiple sclerosis | Bone marrow | None | Mice | ↓Daily mean clinical score ↓Daily mean clinical score ↓Maximal disease score ↓Cumulative disease score |
↓Proliferation of mitogen or antigen-stimulated T-cells ↓IFN- γ ↓IL-2 |
| Adipose tissue | Effectiveness adipose tissue and umbilical cord-derived MSCs > effectiveness bone marrow-derived MSCs | ↓IL-17 (Ad-MSCs and BMSCs only) ↓TNF-α (Ad-MSCs and UC-MSCs only) ↑IL-6 (BMSCs only) |
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| Umbilical cord stroma | ↓Daily mean clinical score ↓Maximal disease score ↓Cumulative disease score |
↑IL-10 (BMSCs only) | ||||
| (129) | Multiple sclerosis | Placenta | Intramuscular implantation of MSCs | Mice | ↓Disease progression | None |
| Direct injection of MSCs into the central nervous system | ↓Clinical score | |||||
| (133) | Multiple sclerosis | Bone marrow | None | Mice | ↓Disease progression ↓Average clinical score ↓Maximum clinical score ↓Demyelination of the lumbar spinal cord ↓Blood-brain barrier permeability |
↓Immune cell infiltration in the lumbar spinal cord ↓IFN-γ in the serum ↓TNF-α in the serum ↑IL-4 in the serum ↑IL-10 in the serum |
| (136) | Multiple sclerosis | Adipose tissue | Administration of MSCs isolated from lean subjects | Mice | ↓Disease progression ↓Clinical score ↑Total distance traveled ↑Moving duration ↑Total velocity ↑Myelin content in the central nervous system Effectiveness MSCs from lean subjects > effectiveness MSCs from obese subjects |
↓Cell infiltration into the central nervous system ↓Proliferation of T cells ↓Proliferation of memory CD44+ T cells |
| Administration of MSCs isolated from obese subjects | ↓Myelin content in the central nervous system | ↑Cell infiltration into the central nervous system ↓Overall size of the lymph nodes ↑Size of the spleen ↑Proliferation of T cells ↑Differentiation of T cells into mature CD4+ and CD8+ T cells ↑IL-1 gene expression (MSCs from lean subjects) ↑IL-6 gene expression (MSCs from lean subjects) ↑IL-12 gene expression (MSCs from lean subjects) ↑PDGF gene expression (MSCs from lean subjects) ↑TNF-α gene expression (MSCs from lean subjects) ↑LIF gene expression (MSCs from lean subjects) ↑ICAM-1 gene expression (MSCs from lean subjects) ↑G-CSF gene expression (MSCs from lean subjects) |
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| (137) | Multiple sclerosis | Bone marrow | None | Mice | ↓Disease progression | ↓T lymphocytes proliferation |
| (138) | Multiple sclerosis | Bone marrow | Administration of PSGL-1/SLeX mRNA-transfected MSCsAdministration of MSCs alone | Mice | ↓Clinical score ↑Neurological function ↑ Myelination Effectiveness PSGL-1/SLeX mRNA-transfected MSCs > effectiveness MSCs alone |
↑Percentage of rolling and adherent cells ↓Proliferation of CD4+ T lymphocytes ↓Lymphocytes infiltration into the white matter of the spinal cord |
| (139) | Multiple sclerosis | Placenta | None | Mice | ↓Disease progression ↓Clinical score |
↓Inflammatory cell infiltration ↓CD4+IL17+ Th17 cells ↓CD11b+Ly6G+ neutrophils ↓CD11b+Ly6C+ inflammatory monocytes ↓Spleen cells proliferation ↓IL-17 ↑IL-4 ↑IL-10 ↓RORγT gene ↑GATA-3 gene |
| (141) | Multiple sclerosis | Adipose tissue | None | Mice | ↓Astrogliosis | ↑GSK3β+ neurons in the spinal cord ↑IL-4 |
| (143) | Multiple sclerosis | Bone marrow | None | Mice | ↓Clinical score ↓Demyelination in the spinal cord ↓Astrocytes Treatment with hBM-MSCs and minocycline > treatment with hBM-MSCs or minocycline alone |
↓Microglia cells ↑NeuN-positive neurons in the gray matter and spinal cord ↓Apoptotic cells ↓IFN-γ ↓TNF-α ↑IL-4 ↑IL-10 |
| (144) | Multiple sclerosis | Umbilical cord stroma | Administration of umbilical cord derived-MSCs previously treated with IFN-γAbsence of stimulation of MSCs with IFN-γ prior to administration | Mice | ↓Clinical scores ↓Disease progression Effectiveness MSCs + IFN-γ > effectiveness MSCs alone |
↓Leukocyte infiltration in the spinal cord white matter ↑CD4+CD25+Foxp3+CD127low/neg Treg cells in cervical lymph nodes cells and splenocytes ↓PBMCs proliferation (in vitro) ↑IL-10 ↑IL-4 ↑HGF ↑VEGF ↑TGF-β ↓IFN-γ ↓IL-17 |
| (145) | Multiple sclerosis | Adipose tissue | None | Mice | ↓Clinical scores ↑Survival rates |
↓Peripheral MOG-specific T-cell responses ↓IFN-γ ↓IL-17A ↓IL-6 ↑IL-4 |
| (130) | Multiple sclerosis | Adipose tissue | None | Rats | ↓Disease progression ↓Mean clinical scores ↓Histopathologic score ↓Vascular congestion ↓Axonal loss of the gray and white matters of cerebral cortex |
↓Immune cell infiltration ↑HLA-G gene expression in lymph nodes and brains ↓CD3 mRNA expression expression in the brain ↓CD19 mRNA expression expression in the brain ↓CD11b mRNA expression expression in the brain ↓IFN-γ in the serum ↓IL-17 in the serum ↑IL-4 in the serum ↑IL-10 in the serum |
| (140) | Multiple sclerosis | Adipose tissue | None | Rats | ↓Duration of paralysis ↓Disease progression ↓Clinical score |
↓Inflammatory cell infiltration in the spinal cord ↑IL-10 gene expression in the lymph node ↑IDO gene expression in the lymph node ↑IFN-γ gene expression in the lymph node |
| (142) | Multiple sclerosis | Umbilical cord stroma | None | Rats | ↓Clinical score | ↓Proliferation of activated T cells ↓Autoantigen-induced T-cell proliferation ↓Dendritic cell differentiation and maturation ↑IDO-1 ↓IFN-γ ↑IL-10 ↑LIF gene ↑PD-L1 gene ↑COX-2 gene ↑TGF- β1 gene ↑TSG-6 gene ↑CD200 gene ↑HGF gene ↑HLA-E gene ↑HLA-G gene ↑HO-1 gene ↑BDNF gene ↑CNTF gene ↑GDNF gene ↑NGF gene ↑NTF3 gene |
| (125) | Multiple sclerosis | Bone marrow | None | Humans | ↓Expanded disability status scale score | None |
| (131) | Multiple sclerosis | Bone marrow | None | Humans | ↓Expanded disability status scale score | ↓CD45RO+ memory T-lymphocytes ↓Myelin-stimulated T cells proliferation |
| (132) | Multiple sclerosis | Bone marrow | None | Humans | ↓Expanded disability status scale score | None |
| (134) | Multiple sclerosis | Bone marrow | None | Humans | ↓Mean cumulative number of gadolinium-enhancing lesions ↓Expanded disability status scale score |
↑ CD19+IL-10+ Breg cells frequency ↓Breg/CD19+ cells ratio ↓Th1/Th17 cells ratio |
| (135) | Multiple sclerosis | Bone marrow | None | Humans | ↓Expanded disability status scale score ↑Sensory function ↑Pyramidal function ↑Cerebellar function |
None |
| (146) | Autoimmune myasthenia gravis | Bone marrow | None | Mice | ↓Mean clinical score | ↓Anti-acetylcholine receptor antibody levels (in the serum) ↓AchR-specific lymphocyte proliferation (in the serum) ↓Mononuclear cells proliferation |
| (147) | Autoimmune myasthenia gravis | Dental pulp | None | Mice | ↓Clinical score ↑Inverted screen hang time ↓Disease incidence ↓Complement component three deposits in the muscle |
↓Anti-muscle-specific tyrosine kinase antibody levels (in the serum) ↓Neuromuscular junction IgG levels (in the serum) ↓CD11b+ leukocytes in lymph nodes ↓IL-6 ↓IL-12 |
| (148) | Autoimmune myasthenia gravis | Bone marrow | None | Humans | ↓Quantitative myasthenia gravis score | ↓Anti-acetylcholine receptor antibody levels (in the serum) |
| (149) | Neuromyelitis optica | Bone marrow | None | Humans | ↑Healing of pressure ulcers ↑Improvement of disability ↑Ability to walk |
None |
Both the methodology employed and the results obtained by each article are represented in this table. MMP-2, matrix metalloproteinase-2; MMP-9, matrix metalloproteinase-9; Ad-MSCs, adipose tissue-derived mesenchymal stem cells; Uc-MSCs, umbilical cord-derived mesenchymal stem cells; BMSCs, bone marrow-derived mesenchymal stem cells; PDGF, platelet-derived growth factor; G-CSF, granulocyte-colony stimulating factor; RORγT, RAR-related orphan receptor gamma T; GSK3β, glycogen synthase kinase 3 beta; TSG-6, tumor necrosis factor-inducible gene 6 protein; HLA-E, human leukocyte antigen E; HLA-G, human leukocyte antigen G; HO-1, heme oxygenase 1; BDNF, brain-derived neurotrophic factor; CNTF, Ciliary neurotrophic factor; GDNF, glial cell-derived neurotrophic factor; NTF3, neurotrophin-3; MOG, myelin oligodendrocyte glycoprotein; AchR, acetylcholine receptor.