The Therapeutic Potential of Inflamed Gingiva-Derived Mesenchymal Stem Cells in Preclinical Studies: A Scoping Review of a Unique Biomedical Waste

Table 2

Results of included studies.

No.	Study ID	Clonogenic potential	Proliferation rate	Population doubling capacity	Phenotypic profile	Trilineage differentiation	Outcome measures	Method of investigation	Endpoint
1	Tang et al., 2011 [6]	I-GMSCs>H-GMSCs	Both sources proliferated similar to each other and faster than BMSCs	I-GMSCs>H-GMSCs>BMSCs	Similar expression/positive: STRO-1, CD29, CD44, CD90, CD105,CD146; negative: CD34, CD45	No significant difference (3 out 3) (osteo-adipo-chond)	Immunoregulation/immunosuppressive; Formation of collagenous tissue	Coculture with T cell allogenic skin model; Histological (H and E) and immunohistochemical analysis	Both cells showed increase ratio of regulatory T cells (Tregs) in comparison to BMSCs; Both cells generated collagenous connective tissue with type 1 collagen was more evident in I-GMSCs
2	Ge et al., 2012 [7]	No significant difference	I-GMSCs>H-GMSCs	H-GMSCs>I-GMSCs	Similar expression/positive: CD44, CD73, CD90, CD105, CD166; negative: CD14, CD34, CD45	Similar capacity (3 out 3)	Formation of collagenous and mineralized tissues	Immunohistochemical analysis	Both GMSCs generated dense collagen tissue, while mineralized tissues observed only in PDLSCs
3	Li et al., 2013 [34]	No significant difference	I-GMSCs>H-GMSCs	Not reported	Similar expression/positive: CD29, CD90, CD44, CD105, STRO-1, CD146; negative: CD34, CD45	Different capacity (2 out 3) osteo+adipo (lower in I-GMSCs)	Osteogenic potential	Alzarin Red staining, ALP staining, RT-PCR	I-GMSCs exhibited lower adipogenic and osteogenic differentiation than H-GMSCs and osteogenic markers were heavily declined after treatment with cytokines
							Formation of collagenous tissue	Histological (H and E) RT-PCR	Inflammatory cytokine-treated GMSCs and DPSCs induced profibrotic phenotype. I-GMSCs had a higher expression of intrinsic cytokines (MMP)-1, MMP-2, IL-1, IL-6, TNF-α, and type 1 collagen than H-GMSCs
4	Yang et al., 2013 [11]	Compare between healthy groups (H-GMSCs and H-PDLSCs)	Compare between healthy groups (H-GMSCs and H-PDLSCs)	Compare between healthy groups (H-GMSCs and H-PDLSCs)	Compare between healthy groups (H-GMSCs and H-PDLSCs)	Compare between healthy groups (H-GMSCs and H-PDLSCs)	Osteogenic potential	Alizarin Red staining, ALP staining, and RT-qPCR/expression of osteogenic markers (OCN, RUNX2, and COL1)	Both cells showed decline in the osteogenic potential, more significantly in PDLSCs compared to GMSCs
							Formation of bone	Histological (H and E, MT staining)	Inflammatory cytokine-treated cells showed decrease in bone formation capacity in comparison to the untreated ones, higher osteogenic area in inf. cytokine-treated PDLMSCs than GMSCs.
5	Fawzy El-Sayed et al., 2016 [15]	# done for H-GMSCs	# done for HGMSCs	ND	# done for H-GMSCs	#done for HGMSCs (3 out 3) (osteo-adipo-chond)	TRL expression profile	Flow cytometry, mRNA expression	H-GMSCs expressed TLRs 1, 2, 3, 4, 5, 6, 7, and 10, while inf. cytokine-treated GMSCs expressed TLRs 1, 2, 4, 5, and 7 as well as 10 without TLR 6
6	Barhanpurkar –Naik et al., 2017 [31]	ND	ND	ND	NR; # done for H-MSCs, but data not presented	ND	IL-3Rα expression profile	Flow cytometry, mRNA expression	The mRNA expression of 3 sources was similar; however, the protein expression was different (BMSCs and ADSCs showed higher expression of IL-3Rα than GTMSCs)
							Migration, motility, and wound healing capacity	In vitro cell migration, motility, and wound healing assays	No significant differences in all three sources; IL-3 enhanced migration, motility, and wound closure.
7	Tomasello et al., 2017 [8]	Significant difference; I-GMSCs and I-DPSCs>H-GMSCs and H-DPSCs	I-DPSCs and I-GMSCs>H-DPSCs and H-GMSCs	I- GMSCs and I-DPSCs>H-GMSCs and H-DPSCs	Slight different expression/positive: STRO-1, CD146, CD29, SSEA4 (higher expressed in diseased groups); negative: CD34, CD45, HLA-DR	ND	Osteogenic potential	Alizarin Red staining and RT-qPCR/expression of osteogenic markers (RUNX2, OPN, and OCN)	Inflammatory cytokine-treated H-DPSCs and H-GMSCs as well as I-MSCs were deeply stained and highly expressed osteogenic markers than untreated H-MSCs.
8	Zhang et al., 2017 [35]	Significant difference; H-GMSCs>I-GMSCs and anti-IGMSCs	Various proliferation rate according to duration; (last time point 12 day) H-GMSCs>I-GMSCs and anti-IGMSCs	ND	# done for H-GMSCs	#done for HGMSCs (3 out 3) (osteo-adipo-chond)	Osteogenic potential	Alizarin Red staining and RT-qPCR/expression of osteogenic markers (RUNX2, ALP, COL1, and OPN)	The number of calcified nodules as well as expression of osteogenic factors were higher in the anti-inflammatory group than in the control group and in the inflammatory group
9	Jauregui et al., 2018 [33]	H-GMSCs>I-GMSCs	Both sources exhibited increase in proliferation rate	ND	Similar expression/positive: CD105, CD73, CD90; negative: CD19, CD34, CD45, CD11b, HLA-DR	Different capacity (2 out of 3) H-GMSCs had higher osteogenicity, while I-GMSCs showed increased adipogenesis	Osteogenic potential	Alizarin Red staining and ALP activity	Both cell sources had a tendency toward osteogenic differentiation.
10	Soanca et al., 2018 [32]	ND	Both sources exhibited Increase in proliferation rate	ND	Similar expression/positive: CD105, CD73, CD90, CD49e, CD29, CD44, CD166; negative: CD14, CD34, CD45, CD79, CD117, HLA-DR	Similar capacity with few cells expressed osteogenic markers (3 out 3+neurogenic).	Testing biocompatibility of resin composite	PKH26 cell membrane fluorescent labeling MTT assay	I-GMSCs can be used as valuable cell line for testing dental material
11	Yu et al., 2019[16]	H-GMSCs>I-GMSCs	H-GMSCs>I-GMSCs	H-GMSCs>I-GMSCs	Different expression/positive: Sca1, CD105, CD90, CD73 (significantly decreased in IGMSCs); negative: CD45, CD34	I-GMSCs showed decrease tridifferentiation potential	Immunomodulation	Coculture with T cells	I-GMSCs showed impaired immunomodulatory properties, and this impairment was rescued when cells treated with acetylsalicylic acid.
12	Al- Bahrawy et al., 2020 [12]	No significant differences	Both sources exhibited increase in proliferation rate	I-GMSCS>H-GMSCs	Positive: CD105, CD73, CD90, CD164; negative: CD14, CD34, CD45	Similar capacity (3 out 3)	Migration capacity	Migration assay	No significant difference between I-GMSCs and H-GMSCs through small pores, while H-GMSCs migrated better than I-GMSCs through large-pore membrane
13	Cristaldi et al., 2020 [13]	I-GMSCs>H-GMSCs	I-GMSCs>H-GMSCs	I-GMSCS>H-GMSCs	Slight different expression/positive: CD73, CD29, CD90, CD105 (slightly increased expression of CD90 and CD105 in IGMSCs); negative: CD45, HLA-DR	(1 out 3) osteogenic	Cell growth	Different cell viability assay	Cell growth or colonization on collagen scaffold was higher in I-GMSCs than H-GMSCs
							Osteogenic potential	Alizarin Red staining and RT-qPCR/expression of osteogenic markers (RUNX2, OCN, and OPN)	Both GMSCs did not grow on nano HA, while they grew effectively on collagen scaffold compared to the unloaded cells/both cells showed a moderate expression of osteogenic markers (RUNX2, OCN, OPN)