Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging.
Akaitz DorronsoroFernando E SantiagoDiego GrassiTianpeng ZhangRuenn Chai LaiSara J McGowanLuise AngeliniMitra LavasaniLana CorboAiping LuRobert W BrooksMarta Garcia-ContrerasDonna B StolzAntonio AmelioSiddaraju V BoregowdaMohammad FallahiAdrian ReichCamillo RicordiDonald G PhinneyJohnny HuardSai Kiang LimLaura J NiedernhoferPaul D RobbinsPublished in: Aging cell (2021)
Aging drives progressive loss of the ability of tissues to recover from stress, partly through loss of somatic stem cell function and increased senescent burden. We demonstrate that bone marrow-derived mesenchymal stem cells (BM-MSCs) rapidly senescence and become dysfunctional in culture. Injection of BM-MSCs from young mice prolonged life span and health span, and conditioned media (CM) from young BM-MSCs rescued the function of aged stem cells and senescent fibroblasts. Extracellular vesicles (EVs) from young BM-MSC CM extended life span of Ercc1-/- mice similarly to injection of young BM-MSCs. Finally, treatment with EVs from MSCs generated from human ES cells reduced senescence in culture and in vivo, and improved health span. Thus, MSC EVs represent an effective and safe approach for conferring the therapeutic effects of adult stem cells, avoiding the risks of tumor development and donor cell rejection. These results demonstrate that MSC-derived EVs are highly effective senotherapeutics, slowing the progression of aging, and diseases driven by cellular senescence.
Keyphrases
- mesenchymal stem cells
- stem cells
- umbilical cord
- endothelial cells
- bone marrow
- cell therapy
- healthcare
- public health
- dna damage
- stress induced
- mental health
- middle aged
- health information
- human health
- health promotion
- induced apoptosis
- high fat diet induced
- ultrasound guided
- gene expression
- mouse model
- oxidative stress
- dna repair
- metabolic syndrome
- cell proliferation
- single cell
- extracellular matrix
- climate change
- insulin resistance
- induced pluripotent stem cells
- signaling pathway
- adipose tissue
- wild type
- endoplasmic reticulum stress
- pluripotent stem cells
- cell death