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. 2021 Jul 26;9:682143. doi: 10.3389/fcell.2021.682143

TABLE 2.

Pre-clinical studies with oral mucosa.

In vivo

Species Cell type or component Method Donor tissue Recipient tissue Outcome Reference(s)
Mouse SCs Injection Deciduous teeth Skin Accelerated wound healing Nishino et al., 2011
Keratinocytes Topical application Human gingiva Skin Rapid re-epithelialisation Kim et al., 2013
Fibroblasts Injection Buccal mucosa Skin Reduced scarring, lineage-dependent behaviour Rinkevich et al., 2015
SC/progenitor cells Salisphere cell transplantation Human submandibular salivary gland Mouse submandibular salivary gland Rescue of saliva production Pringle et al., 2016
Keratinocytes and fibroblasts TEOM Oral mucosa (non-specified) Skin Faster wound healing, reduced scarring Roh et al., 2017
miRNA-31 mimic Injection Hard palate Skin Significant acceleration of wound closure Chen et al., 2019
Keratinocytes and fibroblasts TEOM Human oral mucosa Skin Accelerated wound healing, reduced scarring Lee et al., 2019
Exosomes Injection Human saliva Skin Efficient wound healing through promotion of angiogenesis Mi et al., 2020
SCs Injection Oral mucosa (non-specified) Skin Accelerated wound healing Kuperman et al., 2020

Rat Keratinocytes TEOM Oral mucosa (non-specified) Uterus Highly effective against intrauterine adhesions Kuramoto et al., 2015
Keratinocytes and fibroblasts pre-vascularized TEOM Oral mucosa (non-specified) Buccal mucosa Accelerated and more efficient healing Lee et al., 2017
Exosomes Hydrogel topical application Human gingival mesenchymal SCs Skin Promotion of re-epithelialisation, deposition and remodelling of ECM Shi et al., 2017
Keratinocytes and fibroblasts TEOM Buccal mucosa Skin Accelerated wound healing, reduced scarring Lee et al., 2018
Dental pulp SCs Injection via tail vein Upper and lower incisors Oesophagus Improved healing Zhang et al., 2018
EGF, HA, bFGF and lysozyme Biomimetic hydrogel Commercial Skin Accelerated wound healing, reduced scarring Kong et al., 2019
Mucosal tissue Grafting Tongue Skin Lower levels of EGF and VEGF-C Qi et al., 2019
Exosomes Topical application Human buccal epithelial cell sheets Skin Significant acceleration of wound closure Sjöqvist et al., 2019

Dog Keratinocytes TEOM Buccal mucosa Oesophagus Complete faster wound healing, no stenosis Ohki et al., 2006
Keratinocytes and fibroblasts TEOM Oral mucosa (non-specified) Oesophagus Good distensibility and epithelial thickness, successful oesophageal replacement Nakase et al., 2008
Keratinocytes TEOM Buccal mucosa Oesophagus Successful attachment and re-epithelisation Takagi et al., 2010

Rabbit Dental pulp SCs TEOM Human deciduous teeth Eye Corneal reconstruction Gomes et al., 2010
Keratinocytes TEOM Buccal mucosa Urethra Urethroplasty reconstruction Yudintceva et al., 2020

Goat Epithelial graft Grafting Oral mucosa (non-specified) Trachea Coverage of the constructed trachea lumen Li et al., 2019

Pig Keratinocytes Injection Buccal mucosa Oesophagus Improved re-epithelisation, reduced risk of stenosis and contraction Sakurai et al., 2007

In vitro

Species Cell type Method Donor tissue Outcome Reference(s)

Human Keratinocytes TEOM Gingiva Fabrication of oral mucosal equivalent similar to the native tissue Yoshizawa et al., 2004
Fibroblasts Reprogramming Buccal mucosa Efficient reprogramming into induced pluripotent SCs Miyoshi et al., 2010
Keratinocytes TEOM Cryopreserved lip mucosa Successful fabrication of oral mucosa equivalents Xiong et al., 2010
Fibroblasts Low-level laser therapy Cell line Increased cell number and migration Basso et al., 2012
Keratinocytes TEOM Lip Fabrication of 3D human lip skin equivalent Peramo et al., 2012
Keratinocytes TEOM Keratinised oral mucosa Development of large TEOM Kato et al., 2015
Fibroblasts and immortalised OKF6/TERET-2 oral keratinocytes TEOM Gingiva Development of 3D bone-oral mucosa model Almela et al., 2016
Fibroblasts Feeder cells Gingiva Improved cell proliferation, promising candidate feeder cells Yu et al., 2016
Fibroblasts In vitro differentiation, feeder cells Oral mucosa (non-specified) Fabrication of corneal epithelial sheets, multipotent differentiation into mesenchymal or neural crest-derived cells, good source of feeder cells Higa et al., 2017
Keratinocytes and fibroblasts Scaffolds Buccal mucosa Tri-layer micro-nano-3D porous synthetic scaffold mimics normal human oral mucosa, minimal contraction, good mechanical properties Simsek et al., 2018
Keratinocytes and fibroblasts TEOM Gingiva Development of 3D epithelium and lamina propria Nishiyama et al., 2019

Pig Keratinocytes TEOM Buccal mucosa Culture on acellular scaffolds Poghosyan et al., 2013

Dog Keratinocytes TEOM Buccal mucosa Successful construction of TEOM with adipose derived SCs and small intestine submucosa Zhang et al., 2021

Comparison of the outcomes according to the animal species, the cell type or non-cell component, the method used and the recipient tissue. TEOM, tissue-engineered oral mucosa; EGF, epidermal growth factor; HA, hyaluronic acid; bFGF, basic fibroblast growth factor; VEGF-C, vascular endothelial growth factor C.