Dawn of a new era in olfactory regeneration: Pediatric stem cell therapy enters the era of long-term validation

Table 1 Representative animal and early experimental studies investigating cell-based interventions for olfactory dysfunction

Ref.	Cell type	Study model	Route of administration	Evaluation period	Main outcome
Kurtenbach et al[15], 2019	c-KIT(+) globose basal cells (olfactory progenitors)	Mouse (hyposmia model)	Intranasal droplet delivery	3-4 weeks (EOG/histology); 8-10 weeks (behavior)	Intranasally delivered c-KIT(+) progenitors generated olfactory neurons and restored function
Jiang et al[16], 2025	Human olfactory neurospheres	Mouse (methimazole-induced hyposmia)	Intranasal delivery	4 weeks (histology/behavior)	DNS-ONS showed superior regenerative capacity and function restoration compared to CRS-ONS
Ishikura et al[11], 2023	Mouse ADSCs	Mouse (methimazole-induced OE damage)	Nasal administration	14 days [histology (aversion test)]	ADSCs promote OE regeneration (OMP increase) and support the recovery of odor aversion behavior
Kim et al[17], 2009	Rat ADSCs	Rat (olfactory nerve transection)	Intravenous injection	30 days (histology)	Systemic ADSCs promote OE regeneration (OMP/PCNA increase) following nerve transection
Franceschini et al[18], 2014	Human ADSCs	Mouse (dichlobenil-induced OE lesion)	Tail vein injection	30 days and 60 days (EOG/histology)	Human ADSCs engraft, induce OE regeneration, and restore functional reactivity (EOG)
Hazir et al[19], 2025	NSCs	Mouse (3-MI-induced anosmia)	Intranasal delivery	2 weeks (early histology); 4 weeks [histology/behavior (FFT)/PCR]	NSCs transplantation promotes functional recovery (FFT) and OE epithelial repair
Lee et al[9], 2010	NSCs	Mouse (3-MI-induced anosmia)	Intranasal delivery	4 weeks [histology/behavior (FFT)/western blot]	NSCs transplantation promoted recovery of olfactory function and improved survival
Jo et al[20], 2015	BMSCs	Rat (TX-100-induced OE damage)	Direct OE injection	2 weeks and 4 weeks [histology/behavior (FFT)/IHC/qRT-PCR]	BMSCs transplantation promoted OE and olfactory function restoration, associated with NGF and BDNF regulation

EOG: Electro-olfactogram; DNS: Deviated nasal septum; ONS: Olfactory neurospheres; CRS: Chronic rhinosinusitis; ADSCs: Adipose-derived stem cells; OE: Olfactory epithelium; OMP: Olfactory marker protein; PCNA: Proliferating cell nuclear antigen; NSCs: Neural stem cells; 3-MI: 3-methylindole; FFT: Fast Fourier transform; PCR: Polymerase chain reaction; IHC: Immunohistochemistry; qRT-PCR: Quantitative real-time polymerase chain reaction; BMSCs: Bone marrow-derived mesenchymal stem cells; NGF: Nerve growth factor; BDNF: Brain-derived neurotrophic factor.