Therapeutic applications of dental pulp stem cells in regenerating dental, periodontal and oral-related structures

Table 1 Preclinical studies obtained from the PubMed, Scopus and Google Scholar databases related to dentin-pulp complex regeneration using dental pulp stem cells

Ref.	Strategy	Model	Defect/site of cell implantation	Cell number	Cell source	Cell application
Wang et al[11], 2011	Scaffold-based	Nude mice	Subcutaneous implantation	1 × 106	hDPSCs	Loaded on the top surface of the scaffold
Pan et al[12], 2013	Scaffold-based	Nude mice	Subcutaneous implantation	1 × 106	DP progenitors	Mixed with collagen sponge sheets and SCF
Horibe et al[13], 2014	Scaffold-based	SCID mice	Subcutaneous implantation	1 × 106	hDPSCs	Loaded into human tooth root model
Chaudhary et al[14], 2016	Scaffold-based	Nude mice/ nude rats	Subcutaneous implantation/ first molar root canal	8 × 106	hDPSCs	Loaded into rabbit molar pulp cavity/ cell injection into root canals
Zhang et al[15], 2017	Scaffold-base	Nude mice	Subcutaneous implantation	Not detected	hDPSCs	Mixed with porous calcium phosphate cement

hDPSCs: Human dental pulp stem cells; SCF: Stem cell factor; SCID: Severe combined immunodeficiency.

Table 2 Preclinical and clinical studies obtained from the PubMed, Scopus and Google Scholar databases related to periodontal tissue regeneration using dental pulp stem cells

Ref.	Strategy	Model	Defect/site of cell implantation	Cell number	Cell source	Cell application
Khorsand et al[25], 2013	Scaffold-based	Mongrel dogs	3-walled PDs with ligature induced periodontitis	2 × 107	Autologous dogs' DPSCs	Loaded on the top surface of the scaffold
Ma et al[26], 2014	Scaffold-free	Miniature pigs	Bone defect of 5 mm width, 7 mm length, and 3 mm depth	1 × 107	hDPSCs	Cell injection
Cao et al[27], 2015	Scaffold-free	Miniature pigs	Bone defects of 5 mm width, 7 mm length, and 3 mm depth	1 × 107	hDPSCs transfected with adenovirus-mediated transfer of HGF gene	Cell sheet transplantation or cell injection
Hu et al[28], 2016	Scaffold-free	Miniature pigs	Bone defect of 5 mm width, 7 mm length, and 3 mm depth	1 × 107	hDPSCs	Cell sheet transplantation or cell injection
Li et al[29], 2019	Scaffold-based	Miniature pig	Periodontal defect of 5 mm × 6 mm × 5 mm	1 × 107	Autologous pig DPSCs-IPs	loaded onto the scaffold
Lin et al[30], 2020	Scaffold-based	Sprague-Dawley rats	Periodontal defect adjacent to the root of the second molars	2 × 106	hDPSCs	Cell injection
Meng et al[31], 2020	Sandwich structure	Nude mice	Subcutaneously (bioroot regeneration)	5 × 105	hDPSCs	Cell sheet
Shen et al[32], 2020	Scaffold-based/cell-free therapy	Mouse	Periodontitis created using 5-0 silk ligature	50 μg	hDPSCs-Exo	Incorporated onto the scaffold and combination injected locally
Li et al[33], 2016	Scaffold-based	Human	Periodontal intrabony defects	1 × 105	Autologous DPSCs-IPs	Loaded onto the scaffold material
Ferrarotti et al[34], 2018	Scaffold-based	Human	Chronic periodontitis with deep intrabony defect	50 μm micrograft	Micrografts rich in autologous hDPSCs	Seeded onto the scaffold
Aimetti et al[35], 2018	Scaffold-based	Human	Chronic periodontitis with deep intrabony defect	50 μm micrograft	Micrografts rich in autologous hDPSCs	Loaded on the scaffold
Hernández-Monjaraz et al[36], 2020	Scaffold-based	Human	PDs, without uncontrolled systemic chronic diseases	5 × 106	hDPSCs	Dripped suspended in 200 mL of PBS and then collagen membrane was placed

DPSCs: Dental pulp stem cells; hDPSCs: Human dental pulp stem cells; HGF: Hepatocyte growth factor; IPs: Inflammatory dental pulp tissues; PBS: Phosphate-buffered saline; PDs: Periodontal defects.

Table 3 Preclinical studies obtained from the PubMed, Scopus and Google Scholar databases related to salivary gland regeneration using dental pulp stem cells

Ref.	Strategy	Model	Defect/site of cell implantation	Cell number	Cell source	Cell application
Janebodin et al[42], 2012	Scaffold-based	Rag1 null mice	Injected ventrally onto SMG without penetrating the gland	1 × 106	Murine DPSCs	100 μL of cell suspension
Yamamura et al[43], 2013	Scaffold-free	C57BL/6J green fluorescent protein-expressing mice	Irradiated SMG	2 × 106	Murine DPSCs	5 μL of single cell suspension was injected intraglandular using a 28 G needle and microliter syringe.
Narmada et al[44], 2020	Scaffold-free	Wistar rats	SMG of diabetic rat model	5 × 105	hDPSCs	Intraglandular cell injection.
Takeuchi et al[45], 2020	Cell-free	ICR mice	SMG duct ligation	0.4 mL	hDPSCs	DPSCs-CM was administered via the right jugular vein biweekly under general anaesthesia.

DPSCs: Dental pulp stem cells; hDPSCs: Human dental pulp stem cells; SMG: Submandibular.

Table 4 Preclinical and clinical studies obtained from the PubMed, Scopus and Google Scholar databases related to bone regeneration using dental pulp stem cells

Ref.	Strategy	Model	Defect/site of cell implantation	Cell number	Cell source	Cell application
Yamada et al[49], 2010	Scaffold-free	Dogs	Mandibular bone defects were prepared using a trephine bur with a diameter of 10 mm	1 × 107	hDPSCs	Cavities filled with DPSCs/PRP
Liu et al[50], 2011	Scaffold-based	Rabbit	A segmental critical size defect (10 mm × 4 mm × 3 mm) was prepared in the alveolar bone	1 × 106	Autologous DPSCs	DPSCs were seeded onto nano- hydroxyapatite/collagen/PLLA and implanted in-vivo
Fujii et al[51], 2018	Scaffold-free	Mice	3.5 mm calvarial defects	NA	Autologous DPSCs	Cell sheet transplantation
Mohammed et al[52], 2019	Scaffold-based	Rabbit	Craniofacial bone defect in the left side of TMJ	2 × 106	hDPSCs	DPSCs were loaded on gel foam
Chamieh et al[53], 2019	Scaffold-based	Rat	Non-critical defects of the tibia in rats	106 cells/mL	hDPSCs	Loaded on a lyophilized and hydrolyzed collagen sponge (Hemospon®)
d’Aquino et al[54], 2009	Scaffold-based	Human	Defect without walls, of at least 1.5 cm in height	1 × 107	Autologous DPSCs	Cells endorsed with a syringe onto collagen sponge scaffold

DPSCs: Dental pulp stem cells; hDPSCs: Human dental pulp stem cells; NA: Not available; PRP: Platelet-rich plasma.