Immunomodulatory Functions of Mesenchymal Stem Cells in Tissue Engineering

Table 2

Organ	MSC source	MSC pretreatment	Scaffold type	Immunomodulatory	Reference
Cartilage	Rabbit bone marrow-derive	IFN-g	Hydrogel scaffold	The hydrogel structure helps to reduce the immune response of MSCs after vaccination, even in the presence of inflammation cytokines.	[125]
	Human bone marrow-derived	IFN-g TNF-a	Alginate/hydrogel scaffold	MSCs under 3D hydrogel have low immunogenicity and can exert an immunosuppressive effect on HLA-mismatched PBMCs. And it has an inhibitory effect in NK cell-mediated cytolysis.	[123]
	Human bone marrow-derived	Overexpression of IL-1 receptor antagonist in MSCs induced by lentivirus	Woven PCL scaffold	Enhancement of collagen/GAG production in scaffolds expressing IL-1Ra under inflammatory conditions; MMP was reduced in the construct compared to the untreated group, and the level of PGE2 was elevated.	[124]
	Rat bone marrow-derived	No	Hydrogel-sponge concentration	The production of NO, PGE2, HGF, and IDO increased gradually in 2D culture, and the immunoregulatory factor secreted by MSC in the 3D group reduced the activation ability of allogeneic lymphocytes.	[126]
	Pig bone marrow-derived	No	Cylindrical unwoven PGA fiber	The cytokines IL-10 and TGF-b were increased in the construction group, and the ability of FBGC recruitment was decreased.	[70]
	Human umbilical cord-derived	No	Decellularized pig ECM scaffold	Molecular IDO, PEG2, TGF-b1, IL-10, VEGF, and HGF increased in the scaffold concentration group.	[127]
	Rat bone marrow-derived	TNF-a	Freeze-dried collagen scaffolds	The scaffold construct group exhibited an immunosuppressive potential with a significant increase in iNos. And an upward trend was also observed for Cox and TGF-b.	[122]
Bone	mice bone marrow-derived	No	Transglutaminase glutathionase-crosslinked gelatin (TG-gel)	Cytokines and gene profiles of TNF-a and IL-10 in the scaffold construct showed elevated cincentractions in the test group.	[129]
	Human bone marrow-derived	No	3D instantaneously solidifying material (acBSP)	The scaffold construct synergizes with macrophage to promote cytokine expression of IL-11, IL-17, IL-4, and IL-6 and low expression of IL-1b and TNF-a.	[130]
	Human bone marrow-derived	No	MSC loaded on hydroxyapatite-tricalcium phosphate	After implantation of the scaffold construct, histologically, no lymphocytic infiltration occurred. And new bone was formed throughout the implant.	[131]
	Human bone marrow-derived	IFN-g	ECM	The scaffold construct can induce bone regeneration and inhibit xenografting of mouse T cells in the transplanted area.	[31]
liver	Mice bone marrow-derived	No	MSC transplantation	In the experiment group, TNF-a, IFN-g, IL-2, IL-17, IL-1b, and MPO secretion was decreased, and IL-10 was reversed. Expression of CXCL1, CCL2, CCL4, CCL7, and CXCL10 was inhibited.	[135]
	Rat bone marrow-derived	No	MSC transplantation	The expression of TNF-a, IL-1b, CXCL1, and CXCL2 was decreased, and the expression of the anti-inflammatory cytokine IL-10 was increased.	[136]
	Human umbilical cord-derived	No	3D spheroid	PGE2 secreted by the 3D group was significantly increased, and IFN-g was decreased.	[137]
Heart	Mice bone marrow-derived	No	Decellularized ECM	MSC vaccination results in positive immunomodulatory effect but a persistent chronic inflammatory response.	[149]
	Rat bone marrow-derived	No	3D hydrogel	Compared with the control group, the scaffold construct played a role in inhibiting leukocyte and promoting repair in the late stage of inflammation.	[150]
	Human bone marrow-derived	Simulated inflammatory environment	3D collagen scaffold	The immunosuppressive function of MSCs is retained in the 3D scaffold and promotes the activation of M2 macrophage. Single-layer cocultures with IL-10 levels lower than MSCs	[151]
	Rat bone marrow-derived	No	PCL	For the infiltration of CD68(+) macrophage in the absence of the scaffold construct, and the control group had a higher number of CD68(+)	[152]