Table 2.
Preconditioning with drugs and small molecules regulating MSC senescence.
| Biomolecules /Chemicals | MSC type | Target | Effect | Ref. |
|---|---|---|---|---|
| Rapamycin | BM-MSC | 1. Target to autophagy 2. Target to the Akt/mTOR pathway |
1. Restore the bone loss in aged MSCs 2. Prevents the development of an age-related phenotype and maintains MSC morphology of early passage cells |
[102, 143] |
| 5-MTP | BM-MSC | 1. Target to FoxO3a and mTOR 2. Target to mitochondrial function and reducing ROS generation |
Rescue MSCs from Senescence | [144, 145] |
| Melatonin | AD-MSC/ BM-MSC |
1. Target to mitochondrial function and mitophagy 2. Target to ROS and p53/ERK/p38 3.Target to PrPC and mitochondrial function 4. Target to the SIRT1-dependent pathway |
Rescue MSC from senescence | [146-149] |
| Resveratrol | AD-MSC/ UC-MSC/ BM-MSC |
1. Target to the p-Akt expression 2. Target to the SIRT1 3. Target to the mitochondrial autonomous gene transcription |
1. Enhance AD-MSCs viability 2. Promote cell viability and proliferation, mitigate senescence of UD-MSCs 3. Improve mitochondrial functional recovery and osteogenic differentiation of senescent BM-MSCs |
[150-153] |
| SRT1720 | BM-MSC | Target to the SIRT1 and FAIM | Improve survival of aged MSCs | [154] |
| Metformin | AD-MSC | 1. Target to the SOD 2. Target to NF-κB and SASP |
1. Reduce expression of senescence markers and decreased amount of ROS 2. Inhibit MSC senescence and DNA damage |
[155, 156] |
| Curculigoside | BM-MSC | Target to the TAZ expression | Increase osteogenesis and decrease adipogenesis of aged BM-MSCs | [157] |
| Vitamin C/ Ascorbic acid | SCB-MSC/ BM-MSC |
1. Target to the prelamin A expression 2. Target to ROS and the AKT/mTOR signaling pathway |
Reverse aging in MSCs | [100, 158] |
| Coenzyme Q10 | BM-MSC | Target to the Akt/mTOR signaling pathway | Inhibit MSC aging | [103] |
| Cholesterol | BM-MSC | Target to the cell cycle, autophagy, and ROS/p53/p21 signaling pathways | Rejuvenate MSC senescence | [159] |
| Senolytics and Senomorphic | BM-MSC/ synovial MSC | Target to remove senescent cells | 1. Improve proliferation and osteogenic capacity of aged BM-MSCs 2. Promote the stemness properties of MSC |
[161-164] |
| FGF21 | BM-MSC | Target to the AMPK signaling pathway | Reduce ROS and inhibite MSC senescence | [73] |
| IGF-1 | BM-MSC | Target to the osteogenic potential | Increase the proliferation rate and osteogenic potential of agd BM-MSCs | [165] |
| NDNF | BM-MSC | Target to the p-Akt pathway | Rejuvenate aged MSCs | [166] |
| Nrf2 | UC-MSC | Target to IDO-1 expression | Regulation of the immunosuppressive properties and cellular senescence of MSCs | [167] |
| Nanog | BM-MSC | Target to the TGF-β pathway | Enhanced the proliferation rate and clonogenic capacity of aged BM-MSCs | [168] |
| Lipocalin-2 and prolactin | BM-MSC | Target to mimic the bone marrow niche | Delay cellular senescence of BM-MSCs | [169] |
| MIF | BM-MSC | Target to autophagy | Induce MSC senescence | [170, 171] |
| SB203580 | ED-MSC | Target to the p38MAPK pathway | Recover senescence phenotype | [172] |
| Extracellular vesicles (EVs) | BM-MSC | Target to the IGF1/PI3K/AKT pathway transferring PCNA the miR-183-5p target heme oxygenase-1 (Hmox1) |
improve the function and stemness of MSCs | [174-178] |