The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

Table 1

Experimental studies of MSC therapy in IBD/IBD-associated CRC.

MSC source/type	Model used	Route of administration	Condition	Vital mechanisms	Outcome	Reference
Adipose/allogeneic	BALB/c mice	Intraperitoneal injection	Colitis in CD	(i) Downregulation of Th1; (ii) Impaired Th1 cell expansion; (iii) Induced/activated CD4+CD25+FoxP3+ regulatory T cells	(i) Ameliorated clinical and histopathologic severity of colitis; (ii) Abrogated body weight loss, diarrhea, and inflammation; (iii) Increased survival	[96]
Umbilical cord	C57BL/6 mice	Intravenous injection	AOM and DSS-induced colitis-associated CRC	(i) Decreased expression of Ki-67; (ii) MSCs secreted TGF-β to induce Treg cells from naïve T cells; (iii) Activated Smad2 signaling	(i) Longer colon length and decreased tumor numbers; (ii) Alleviated pathology of inflammation and inhibited inflammation cytokines; (iii) Suppressed development of colitis-associated CRC	[100]
Bone marrow	C57Bl/6 mice	Tail vein or intraperitoneal; Injection	TNBS induced colitis	Increased Foxp3+ splenocytes/regulatory T cells in a CD11b+ cell-dependent manner	(i) Improved symptoms of colitis; (ii) Improved survival (tail vein injection); (iii) No significant improvement in survival (intraperitoneal inj); (iv) Nearly complete absence of occult blood in feces; (v) Inhibited histopathological changes in gut-associated tissue	[88]
Adipose	SD-OFA rats	Endoscopic submucosal injection	TNBS-induced colitis	Recovered Foxp3 and IL-10 mRNA levels	(i) Weight lose recovered; (ii) Improved endoscopic score; (iii) Significantly recovered colon length	[41]
Adipose	Balb/c mice	Intraperitoneal injection	TNBS and DSS induced colitis	(i) ASCs induce a distinct regulatory activation state of macrophages; (ii) High arginase activity and increased production of IL-10; (iii) Immunosuppression of T-cells and macrophages; (iv) Activation of cyclo-oxygenase-2	(i) Inhibited colitis reducing mortality and weight loss; (ii) Reduced levels of inflammatory cytokines; (iii) -Reduced transmural inflammation, mucin-producing goblet cell depletion, epithelial ulceration, disseminated fibrosis, focal loss of crypts, and infiltration of inflammatory cells	[90]
Umbilical cord	Mice	Intravenous injection	TNBS-induced colitis	Down-regulated levels of IL-17, IL-23, IFN-γ, and IL-6	(i) Improved clinical and pathological signs of colitis; (ii) Effectively ameliorated colitis	[95]
Bone marrow	BALB/c mice	Intravenous injection	TNBS-induced colitis	(i) Activated CD4+CD25+Foxp3+ regulatory T cells (TGF-β, IL-10, Foxp3); (ii) Downregulated Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt); (iii) Upregulated Th2 activities (IL-4, IL-10, GATA-3)	(i) Ameliorated clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation; (ii) Increased survival; (iii) Promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells	[94]
Umbilical cord	NOD.CB17-Prkdc^scid/J mice	Tail vein injection	DSS induced colitis	(i) Decreased MPO levels hence reduced neutrophil infiltration; (ii) Decreased MMP2 and MMP9 activities	(i) Significantly reduced DAI with attenuated presence of bloody stools, weight loss and colon length.; (ii) Reduced inflammation and inflammatory cell infiltration, crypt damage, and edema of submucosa	[101]
Umbilical cord	BALB/c mice	Intraperitoneal injection	TNBS-induced colitis	(i) Increased Tregs and CD5+ B cells and decreased Th1, Th17 cells; (ii) -CD5+ B cells inhibited T-cell proliferation and produced IL-10	(i) Increased survival rates, relieved symptoms, and improved macroscopic and histologic scores; (ii) Alleviated induced colitis	[93]
Umbilical cord		Intraperitoneal injections	DSS or TNBS-induced colitis	(i) Increased IL-10 and Treg cells, and decreased inflammatory cytokines; (ii) NOD2 signaling suppressed mononuclear cell proliferation by inducing production of PGE2.; (iii) Reduced MPO activity and infiltration of CD4+ and CD11b+ cells	(i) Reduced severity of colitis and recovered loss of body weight and decreased mortality; (ii) -Abrogated colitis-induced lethality, improved DAI, restored colon length; (iii) -Reduced colon mucosal destruction and edema	[26]

Experimental observations obtained from MSC-based therapy in IBD and its associated CRC. In each observation, route of administration, type of IBD as well as vital mechanisms, and final outcome of the therapy are outlined.