Potential therapeutic applications of antler stem cells and their derivatives

Table 2 Summary of preclinical applications of antler stem cells and related antler-derived products

Organ/indication	Preparation	Model	Intervention route	Principal effect	Mechanism (where defined)	Evidence for engraftment or paracrine action	Ref.
Skin/acute wound	CM; living AnSCs	Rat; radiation wound	Local perilesional delivery	Scarless regenerative healing	Anti-myofibroblast; regenerative substances	Living AnSCs: Donor-cell retention in healing dermis demonstrated, supporting partial direct participation; CM/EV studies: Paracrine	[20-23]
Skin/diabetic, burn	Exosomes; CM-hydrogel	Mouse/rat; full-thickness wound	Local (perilesional injection or topical hydrogel)	Accelerated healing	miR-21-5p/STAT3; angiogenesis; M2 polarization	Cell-free; paracrine modulation of fibroblasts, endothelial cells and macrophages	[24-26]
Bone	EVs; CM; peptides; grafts	Mouse, macaque, rabbit, rat; bone injury/osteoporosis	Local biomaterial implantation or systemic intravenous EV delivery	Bone regeneration; reversal of bone loss	Runx2/Cbfa1; JUN	Stable donor-cell differentiation not conclusively established; CM, EV, peptide and graft effects are host-mediated	[9,10,29-33]
Cartilage/OA	Exosomes; CM; ECM	Rat, mouse; full-thickness osteochondral defect/osteoarthritis	Local scaffold implantation or intra-articular exosome injection	Osteochondral & cartilage repair; anti-OA	miR-140/MMP13; anti-senescence	Predominantly cell-free; stimulation of host chondrocytes and resident progenitors	[35-39]
Liver	AnSCs; thymosin β10	Rat; CCl4-induced liver fibrosis	Intravenous cell transplantation or antler thymosin β10 (intraperitoneal protein delivery)	Reduced fibrosis	TGF-β1/SMAD inhibition	Living-cell treatment, but donor-cell differentiation not demonstrated; transwell evidence supports paracrine action	[43,44]
Lung	Exosomes	Mouse; bleomycin-induced pulmonary fibrosis	Intravenous tail-vein injection	Reduced pulmonary fibrosis	Blocked monocyte/macrophage recruitment	Cell-free EV-mediated immunomodulation	[45]
Nervous system/SCI	Engineered EVs; exosomes; peptides	Rat; postoperative cognitive dysfunction and acute spinal cord trauma	Systemic or local delivery	Neuroprotection; SCI repair	TLR2/TLR4 inhibition	Cell-free EV or peptide effects; no donor-cell engraftment	[47,48]
Diabetes (T1DM)	CM	Mouse; streptozotocin-induced T1DM	Intraperitoneal injection	Disease alleviation	NF-κB inhibition	CM-mediated paracrine effect	[49]
Cancer	AnSC medium; EV carriers	Human prostate cancer cell lines, glioma cell lines, mouse	In vitro cell incubation/intravenous tail-vein injection	Anti-tumor; drug delivery	-	Cell-free anti-tumor activity or EV-mediated drug delivery	[50-52]
Aging	EVs; extract; metabolite	Mouse, macaque; senescence, aging-associated bone loss, skin aging, osteoarthritis	Delivery routes included intravenous, intra-articular, local wound injection or topical application	Anti-senescence; systemic rejuvenation	Uridine; anti-senescence	Cell-free systemic effects; no cellular engraftment	[9,11,28,39]

CM: Conditioned medium; AnSCs: Antler stem cells; EV: Extracellular vesicle; STAT3: Signal transducer and activator of transcription 3; OA: Osteoarthritis; ECM: Extracellular matrix; MMP13: Matrix metalloproteinase-13; TGF: Transforming growth factor; SCI: Spinal cord injury; TLR: Toll-like receptor; T1DM: Type 1 diabetes mellitus; NF-κB: Nuclear factor kappa B.