TABLE 3.
Novel antiaging treatments via extracellular vesicles
| Treatments and sources | Cargo(s) | Subjects | Mechanism(s) and Effect(s) | Ref. |
|---|---|---|---|---|
| Stem cell‐derived therapeutics | ||||
| Hypothalamic stem cells | miRNAs | Aged mice | Blocked NF‐κB activation and restored GnRH secretion in neurons; Reduced age‐related physiological deficits and extended lifespan | (Zhang et al., 2017) |
| Human umbilical cord MSCs | LncRNA MALAT1 | Cardiomyocytes with H2O2‐induced aging; Mice with D‐galactose‐induced aging | Inhibited the NF‐κB/TNFα pathway; increased TERT expression; Increased the left ventricular ejection fraction and fractional shorting in aging mice | (Zhu et al., 2019) |
| Human umbilical cord MSCs | / | UVB‐irradiated HDFs | Reduced production of ROS and increased glutathione peroxidase; Inhibited UVB‐induced senescence and induced fibroblast proliferation | (Deng et al., 2020) |
| ADSCs | / | IL‐1β‐treated OA osteoblasts | Reduced inflammatory mediators including IL‐6 and prostaglandin E2; Controlled mitochondrial membrane stability and reduced oxidative stress | (Tofino‐Vian et al., 2017) |
| ADSCs | miRNAs Proteins | UVB‐irradiated HDFs | Induced senescent fibroblast proliferation and DNA repair and attenuated aging; Suppressed the expression levels of MMP‐1, 2, 3, and 9 and enhanced collagen; Provided protection from UVB irradiation and enhanced recovery from skin photoaging | (Choi et al., 2019) |
| ADSCs | / | Myocardial infarction mice, myocytes, fibroblasts, and macrophages | Activated S1P/SK1/S1PR1 signaling and promoted M2 polarization; Suppressed cardiac dysfunction, apoptosis, fibrosis, and the inflammatory state | (Deng et al., 2019) |
| ADSCs | / | Photoaging mice and fibroblasts | Attenuated macrophage infiltration and ROS production; Promoted cell proliferation and decreased skin wrinkles | (Xu et al., 2020) |
| Human iPSCs | / | Aged and UVB‐irradiated HDFs | Reduced the expression levels of SA‐β‐Gal and MMP1, 3; Restored collagen type I and ameliorated UVB‐induced skin aging | (Oh et al., 2018b) |
| Human urine‐derived stem cells | CTHRC1; OPG | Osteoporotic mice | Enhanced osteoblastic bone formation and suppressed bone resorption | (Chen et al., 2019b) |
| Human embryonic stem cells | miR‐200a | Aged mice with pressure‐induced ulcers; Senescent endothelial cells | Downregulated Keap1 and activated the Nrf2 pathway; Enhanced EC proliferation and angiogenesis; Accelerated wound closure and ameliorated senescent phenotypes | (Chen et al., 2019a) |
| Human embryonic stem cells | 4122 proteins | Senescent BMSCs | Rescued the function of senescent BMSCs and promoted proliferation; Induced osteogenic differentiation and reduced age‐related bone loss | (Gong et al., 2020) |
| Embryonic stem cells | Several miRNAs | Vascular dementia mice | Alleviated senescence and loss of hippocampal stem cells; Reduced cognitive decline by activating mTORC1 and promoting TFEB translocation and lysosome resumption | (Hu et al., 2020) |
| Embryonic stem cells | SMAD4, 5 | Aged mice | Activated MYT1 and improved HIF‐2α, NAMPT and SIRT1 levels; Alleviated hippocampal stem cell senescence, reversed cognitive impairment | (Hu et al., 2021) |
| BMSCs | Neprilysin | APP/PS1 AD mice | Reduced Aβ plaques and dystrophic neurites in the cortex and hippocampus | (Elia et al., 2019) |
| Human decidua‐derived MSCs | / | High glucose‐treated fibroblasts; Diabetic mice | Rescued the senescent state via inhibition of RAGE and activation of Smad; Accelerated collagen deposition and enhanced diabetic wound healing | (Bian et al., 2020) |
| Amniotic fluid MSCs | miR‐21 | Mice with premature ovarian dysfunction | Increased total follicular counts and AMH levels and restored regular oestrous cycles by modulating the PTEN and caspase 3 apoptotic pathway | (Thabet et al., 2020) |
| Amniotic fluid MSCs | miR‐320a | Mice with premature ovarian insufficiency; POI human granulosa cells | Decreased SIRT4 and ROS levels; Improved proliferation, inhibited apoptosis and elevated ovarian function | (Ding et al., 2020) |
| Dental pulp stem cells | miR‐302b | Senescent dental pulp stem cells | Improved stemness through HIF‐1α and OSKM upregulation; Switched energetic metabolism toward glycolysis through the ERK pathway | (Mas‐Bargues et al., 2020) |
| Modified stem cell therapeutics | ||||
| GAG‐coated matrix vesicles | / | BMSCs | Promoted differentiation of osteoblasts from hBMSCs and reduced osteoclasts | (Schmidt et al., 2016) |
| Serially extruded human iPSCs | Oct4 Nanog | Naturally senescent HDFs | Reduced the senescent state and ameliorated skin aging | (Lee et al., 2020) |
| SHS‐coated MS Exos | / | Photoaging mice | Enhanced skin absorption of exosomes by creating microchannels; Reduced wrinkles and promoted extracellular matrix constituents | (Zhang et al., 2020) |
| BMSC Exos with aptamer | miR‐26a | Mice with OVX‐induced osteoporosis; Femur fracture mouse model | Promoted bone regeneration and accelerated bone healing; Enhanced bone targeting and bone generation | (Luo et al., 2019) |
| MSC Exos in silk fibroin hydrogel | miR‐675 | Aged animal model; H2O2‐treated H9C2 cells | Prolonged the half‐life of exosomes in vivo; Reduced aging hallmarks and promoted blood perfusion | (Han et al., 2019b) |
| ACE2‐primed endothelial progenitor cell Exos | ACE2 miR‐18a | Aging ECs | Protected ECs from hypoxia/reoxygenation‐induced injury through downregulation of Nox2/ROS | (Zhang et al., 2018a) |
| LPS‐preconditioned BMSC Exos | / | MI mouse model | Increased M2 macrophage polarization upon LPS stimulation; Attenuated inflammation and cardiomyocyte apoptosis | (Xu et al., 2019) |
| Cytokine‐preconditioned MSC Exos | / | APP/PS1 AD mice | Reduced activation of microglia and increased the dendritic spine density; Induced immunomodulatory and neuroprotective effects | (Losurdo et al., 2020) |
| Predifferentiated MSC Exos in 3D‐printed titanium scaffolds | / | BMSCs | Induced osteogenesis and regenerated bone tissue through the PI3K/Akt and MAPK pathways | (Zhai et al., 2020) |
| Other cell‐derived therapeutics | ||||
| Wnt4‐transgenic TECs | Wnt4; miR‐27b | TECs with steroid‐induced aging | Counteracted thymic adipose involution; Reduced age‐related thymic dysfunction | (Banfai et al., 2019) |
| Endothelial cells | / | Senescent fibroblasts; Diabetic mice | Reduced senescent phenotypes through YAP translocation and the PI3K/Akt pathway and promoted wound healing in diabetic mice | (Wei et al., 2020b) |
| 3D human dermal fibroblasts | TIMP‐1 | Photoaging mice | Induced collagen synthesis and antiaging effects | (Hu et al., 2019) |
| Young donor‐derived therapeutics | ||||
| Young mouse serum | eNAMPT | Aged mice | Enhanced NAD+ biosynthesis and controlled oxidative stress; Enhanced physical activity and extended lifespan | (Yoshida et al., 2019) |
| Primary fibroblasts of young human donors | GSTM2 | HGPS fibroblasts; Aged mice | Reduced senescent phenotypes by restoring antioxidant capacity; Prevented lipid peroxidation | (Fafia, Rodriguez‐Navarron‐Labora et al., 2020) |
| Young human serum | / | DOX‐treated cardiomyocytes | Retarded cellular senescence through the miR‐34a/PNUTS pathway | (Liu et al., 2019b) |
| Young mouse serum | miRNAs | Aged mice | Rejuvenated thymic aging and enhanced thymic negative selection | (Wang et al., 2018) |
| Young mouse serum | miRNAs | Aged mice | Reduced aging gene expression and induced telomerase gene expression | (Lee et al., 2018) |
| Centenarian donor‐derived therapeutics | ||||
| Centenarian fibroblasts | RNAseH2C enzyme | Young HDFs | Reduced inflammatory cytokines and upregulated anti‐inflammatory enzymes; Induced M2 polarization and genomic stability | (Storci et al., 2019) |
| Modified nanomedicines | ||||
| Catalase‐loaded exosomes | Catalase | PD mice | Prolonged circulation time and induced neuroprotective and antioxidant effects | (Haney et al., 2015) |