From discarded tissues to therapeutic assets: Optimizing mesenchymal stem cell sources and secretome signatures for clinical translation

Table 1 Mechanisms and therapeutic applications of oral mesenchymal stem cell-derived secretomes

Source	Key mechanism	Therapeutic application	Ref.
GMSCs	Matrix-bound vesicles on 3D microchannels	Reducing stenosis in tracheal regeneration	[20]
GMSCs	Inhibition of mTOR signaling pathway	Anti-aging for skin and vasculature	[18]
GMSCs	miR-148a-3p regulation of Treg/Th17 balance	Precision therapy for rheumatoid arthritis	[15]
GMSCs	Optimized xeno-free culture conditions	High-yield and safe secretome production	[21]
DPSCs	Scalable expansion in hollow fiber bioreactors	Standardized extracellular vesicle manufacturing	[22]
DPSCs	Restoration of tight junction protein expression	Treating aging-related salivary hypofunction	[23]
DPSCs	Inhibition of ROS-MAPK-NF-κB pathway	Anti-inflammation in spinal cord injury	[14]
DPSCs	Osteoinductive EVs in HA/PEG hydrogels	Bone defect repair and mineralization	[24]
DPSCs	Distinct proteomic profiles in 3D spheroids	Culture-dependent osteogenic enhancement	[25]
DPSCs	Hypoxic miR-210-3p targeting NF-κB p105	Alleviating inflammatory osteolysis	[26]
DPSCs	Biomimetic aggregates with decellularized matrix	Whole tooth regeneration	[27]
DPSCs	Antioxidant enzyme induction by senescent EVs	Adaptive response to oxidative stress	[28]
DPSCs	Secretion from carious tissue-derived cells	Dopaminergic neural differentiation	[12]
SHED	Biglycan delivery via youthful sEVs	Rejuvenating aged periodontal bone	[29]
DPSCs	Exosome delivery via HA-vinyl sulfone hydrogels	Protecting subchondral bone in TMJ osteoarthritis	[30]
SHED	miR-330-5p mediated M2 microglia polarization	Motor recovery in traumatic brain injury	[16]
SHED	miR-24-3p targeting IL-1R1/p-p38 MAPK	Alleviating trigeminal neuralgia	[31]
SHED	HIF-1α stabilization and VEGF upregulation	Enhancing angiogenesis in tissue engineering	[11]
SHED	Hypoxic exosomes on bioinspired microspheres	Vascularized bone regeneration	[32]
SHED	miR-1246 activation of macrophage autophagy	Wound healing with itch relief	[33]
SHED	Modulation of histone methylation and NF-κB	Reversing tendon stem cell senescence	[19]
DPSCs	miR-378a targeting Sufu/Hedgehog pathway	Local angiogenesis in inflammatory environments	[17]
PDLSCs	Mechanical force-induced ANXA3 enrichment	Regulating orthodontic bone remodeling	[34]
PDLSCs	Healthy exosome regulation of Wnt signaling	Rescuing osteogenesis in periodontitis	[35]
SCAP	Conditioning with bioceramic iRoot FM	Proliferation under inflammation	[13]
SCAP	Ultrasound-induced sphingomyelinase upregulation	Enhancing EV yield and bioactivity	[36]
DFSCs	ROS-responsive hydrogel delivery system	On-demand antioxidation for pulpitis	[37]

GMSCs: Gingival mesenchymal stem cells; DPSCs: Dental pulp stem cells; SHED: Stem cells from human exfoliated deciduous teeth; PDLSCs: Periodontal ligament stem cells; SCAP: Stem cells from the apical papilla; DFSCs: Dental follicle stem cells; 3D: Three-dimensional; mTOR: Mammalian target of rapamycin; Treg: Regulatory T; Th17: T helper type 17; ROS: Reactive oxygen species; MAPK: Mitogen-activated protein kinases; NF-κB: Nuclear factor kappa B; EVs: Extracellular vesicles; HA: Hyaluronic acid; PEG: Poly ethylene glycol; sEVs: Small extracellular vesicles; IL-1R1: Interleukin-1 receptor type 1; HIF-1α: Hypoxia inducible factor-1 alpha; VEGF: Vascular endothelial growth factor; ANXA3: Annexin A3.