Table 5.
List of in vivo studies in which the therapeutic potential of the administration of hMSCs for the treatment of chronic inflammatory disorders of the intestine was evaluated and the results obtained.
| References | Autoimmune disease | Source of hMSC | Variables | Experimental model | Clinical and laboratory effects | Mechanism proposed |
|---|---|---|---|---|---|---|
| (155) | Ulcerative colitis | Umbilical cord | None | Mice | ↓Clinical score ↓Weight loss ↑Survival rates ↓Colon pathology |
↑Infiltration of CD4+CD25+FoxP3+ Tregs in the colon ↓Infiltration of CD11b+ leukocytes in the colon ↓Infiltration of CD4+ lymphocytes in the colon ↓Proliferation of mononuclear cells ↑PGE2 ↑IL-10 ↓IL-6 ↓IFN-γ ↓TNF-α |
| (156) | Ulcerative colitis | Adipose tissue | None | Mice | ↓Clinical score ↓Colon pathology ↓Weight loss ↑Survival rates |
↓Th1-cell activation in colonic mucosa and draining lymph nodes ↑CD4+CD25+FoxP3+IL-10+ Tregs in the mesenteric lymph node ↓IL-6 ↓IL-12 ↓IL-1β ↓IFN-γ ↓TNF-α ↓CCL5 ↓CXCL2 ↑IL-10 |
| (99) | Ulcerative colitis | Gingiva Bone marrow | None | Mice | ↓Clinical score ↓Colon pathology ↓Weight loss |
↓Peripheral blood lymphocyte proliferation ↑Infiltration of CD4+CD25+ FoxP3+ Tregs in the colon ↓Infiltration of CD4+ lymphocytes in the colon ↑IL-10 ↑IDO ↑iNOS ↑COX-2 ↓IL-6 ↓IL-17 ↓IFN-γ |
| (100) | Ulcerative colitis | Umbilical cord Adipose tissue | None | Mice | ↓Clinical scores ↓Colon pathology ↓Weight loss |
↓IL-6 in the serum ↓IL-17 in the serum ↓TNF-α in the serum ↓IL-1β in the serum ↓IFN-γ in the serum ↓IL-10 in the serum |
| (101) | Ulcerative colitis | Umbilical cord | Administration of late-passage MSCs | Mice | None | ↑COX-2 ↑PGE2 |
| Administration of early-passage MSCs | ↓Weight loss ↑Survival rates ↓Clinical score ↓Colon pathology Effectiveness early-passage MSCs > effectiveness late-passage MSCs |
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| (102) | Ulcerative colitis | Embryonic stem cells | None | Mice | ↓Weight loss ↓Clinical score ↓Colon pathology |
↓T lymphocyte proliferation ↓B lymphocyte proliferation ↑PD-L1 expression |
| (103) | Ulcerative colitis | Embryonic stem cellsAdipose tissueUmbilical cord | None | Mice | ↑Survival rates ↓Weight loss ↓Clinical score ↓Colon pathology |
↓Inflamatory cell infiltration in the colon ↓Cycling CD4 T-cells ↓Activated T cells ↓IL-2 ↓TNF-α ↓IFN-γ |
| (104) | Ulcerative colitis | Adipose tissue | None | Mice | ↑Survival rates ↓Weight loss ↓Clinical score ↓Colon pathology |
↓Intra-colonTNF-α ↓Intra-colon IFN-γ ↓Intra-colon IL-1β ↓Intra-colon IL-6 ↓IL-12 ↓Intra-colon CCL5 ↓Intra-colon CXCL2 ↑Intra-colon IL-10 ↓IFN-γ+Th1 cell expansion ↑CD4+CD25+FoxP3+ Tregs expansion |
| (105) | Ulcerative colitis | Menstrual blood | None | Mice | ↓Disease activity index ↓Weight loss ↓Colon pathology |
↓Intra-colon TNF-α ↓Intra-colon IL-2 ↑Intra-colon IL-4 ↑Intra-colon IL-10 ↓Intra-colon MPO+ neutrophils ↓Intra-colon Mac-1+ macrophages ↓Intra-colon Mac-1+ NK cells ↓Intra-colon Mac-1+ granulocytes ↓CD3+CD25+ active T cells in the spleen ↓CD3+CD8+ T cells in the spleen ↓CD11c+MHC-II+ dendritic cells in the speen ↑CD4+CD25+FoxP3+ Tregs expansion |
| (106) | Ulcerative colitis | Adipose tissue | None | Mice | ↓Weight loss | ↑Adipose-tissue derived MSCs in popliteal, mesenteric parathymic and parathyroid lymph nodes |
| (107) | Ulcerative colitis | Umbilical cord | Administration of extracts of MSCsAdministration of MSCs | Mice | ↓Disease activity index ↓Weight loss ↓Colon pathology ↑Intestinal epithelial barrier Effectiveness administration of extracts of MSCs >effectiveness administration of MSCs |
↓M1 macrophages ↑M2 macrophages ↓Myeloperoxidase activity in the colon ↓Intra-colon CCL2 ↓Intra-colon CXCL9 ↓Intra-colon iNOS ↓Intra-colon IL-17 ↑Intra-colon TGF-β1 ↑Intra-colon IL-10 ↑Intra-colon TNFSF14 |
| ↑Intra-colon CCL1 ↑Intra-colon Arg-1 ↓Intra-colon sICAM-1 ↓Intra-colon IL-1β ↓Intra-colon IL-16 ↓Intra-colon CXCL10 ↓Intra-colon TIMP metallopeptidase inhibitor 1 |
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| (109) | Ulcerative colitis | Bone marrow | Stimulation of MSCs with IFN-γ prior to administrationAbsence of stimulation with IFN-γ | Mice | ↓Weight loss ↑Survival rates ↓Clinical score ↓Colon pathology ↓Serum amyloid A protein Effectiveness MSCs + IFN-γ > effectiveness MSCs alone |
↑IDO ↓PBMC proliferation ↓CD3+ T cells infiltration in the colon ↓Intra-colon TNF-α ↓Intra-colon IL-6 ↓Intra-colon IL-17 ↓Intra-colon IFN-γ ↑Intra-colon IL-4 ↑Intra-colon IL-10 |
| (110) | Ulcerative colitis | Adipose tissue | None | Mice | ↓Weight loss ↑Survival rates ↓Clinical score ↓Disease recurrence ↓Colon pathology |
↑IL-10 secretion ↓IL-12 secretion ↓T cells proliferation ↓Colon neutrophil infiltration ↓Macrophages proliferation ↑Arginase activity ↑COX-2 activity ↓Intra-colon TNF-α ↓Intra-colon IL-6 ↓Intra-colon IL-1β ↓Intra-colon CCL5 ↑TGF-β1 |
| (113) | Ulcerative colitis | Umbilical cord | None | Mice | ↓Clinical score ↓Colon pathology ↓Weight loss |
↓T-cell proliferation ↑IDO |
| (114) | Ulcerative colitis | Dental pulp Bone marrow | Stimulation of MSCs with acetylsalicylic acid prior to administrationAbsence of stimulation with acetylsalicylic acid None | Mice | ↓Weight loss ↓Disease activity index ↓Histologic activity index Effectiveness MSCs treated with acetylsalicylic acid > effectiveness MSCs alone |
↑AnnexinV+7AAD+ apoptotic T cells ↓CD4+IL17+IFN− Th17 cells ↓CD4+IL17−IFN+ Th1 cells ↑CD4+CD25+Foxp3+ Tregs ↓TNF-α ↓IL-6 ↓IL-17 |
| (115) | Ulcerative colitis | Umbilical cord | Stimulation of MSCs with 5-azacytidine prior to administration Absence of stimulation with 5-azacytidine | Mice | ↓Weight loss ↑Survival rates ↓Disease activity index ↓Colon pathology Effectiveness MSCs treated with 5-azacytidine > effectiveness MSCs alone |
↓Infiltration of lymphocytes in the colon ↓Mononuclear cells ↓Jurkat cells ↑COX2 gene ↑PTGES gene ↑PGE2 ↓LIF gene ↓IL-6 gene ↓IL-1β gene |
| (108) | Ulcerative colitis | Bone marrow | None | Pigs | ↓Clinical score ↓Colon pathology ↓Enteric neuropathy associated with intestinal inflammation |
↓CD45+ leucocytes infiltration in the colon ↑Nerve fiber density in the mucosa ↑Morphology of β-tubulin (III)-IR fibers in mucosal and muscular layers of colon sections ↓Myenteric neuronal loss |
| (111) | Ulcerative colitis | Bone marrow | None | Pigs | ↓Weight loss ↓Colon pathology ↓Neuronal cell body hypertrophy in colon |
↓CD45+ leucocytes infiltration in the colon ↓Myenteric neuronal loss |
| (112) | Ulcerative colitis | Bone marrow | None | Pigs | ↓Weight loss ↑Repair of damaged tissue and nerve fibers |
↓CD45+ leucocytes infiltration in the colon wall and the myenteric plexus ↓Myenteric neuronal loss |
| (116) | Crohn's disease | Bone marrow | None | Humans | ↓Crohn's disease activity index score | ↓Peripheral blood mononuclear cell proliferation ↓TNF-α ↑IL-1β ↑IL-6 ↑IL-10 ↓CD4+ T cells in the colon ↑CD4+CD127+ Tregs in the colon |
| (117) | Crohn's disease | Bone marrow | None | Humans | ↓Crohn's disease activity index score | ↑IL-10 ↑TGF-β ↑IL-6 ↓IFN-γ ↓IL-2 ↓Antinuclear autoantibodies ↓Anti-Saccharomyces cerevisiae antibodies |
| (118) | Type II refractory celiac disease | Bone marrow | None | Humans | ↓Stool frequency ↓Weight loss ↓Gut pathology |
↓IL-15 cytokine in the small intestinal mucosa ↓IL-15 receptor in the small intestinal mucosa |
Both the methodology employed and the results obtained by each article are represented in this table. iNOS, inducible nitric oxide synthase; MPO, myeloperoxidase; Mac-1, macrophage-1 antigen; TNFSF14, tumor necrosis factor superfamily member 14; CCL1, C-C motif chemokine ligand 1; Arg-1, arginase 1; sICAM-1, soluble intercellular adhesion molecule-1; IL-16, interleukin 16; CXCL10, C-X-C motif chemokine 10; PTGES, prostaglandin E synthase; LIF, leukemia inhibitory factor.