Abstract
Cellular senescence of renal tubular cells is associated with chronic diseases and age-related kidney disorders. Therapies to antagonize senescence are, therefore, explored as novel approaches in nephropathy. Exosomes derived from human mesenchymal stroma-/stem-like cells (MSC) entail the transfer of multiple bioactive molecules, exhibiting profound regenerative potential in various tissues, including therapeutic effects in kidney diseases. Here, we first demonstrate that exosomes promote proliferation and reduce senescence in aged MSC cultures. For potential therapeutic perspectives in organ rejuvenation, we used MSC-derived exosomes to antagonize senescence in murine kidney primary tubular epithelial cells (PTEC). Exosome treatment efficiently reduced senescence while diminishing the transcription of senescence markers and senescence-associated secretory phenotype (SASP) factors. Concomitantly, we observed less DNA damage foci and more proliferating cells. These data provide new information regarding the therapeutic property of MSC exosomes in the development of renal senescence, suggesting a contribution to a new chapter of regenerative vehicles in senotherapy.
Highlights
As the population ages, challenges of age-associated diseases are steadily growing and pose an enormous burden to public health
We explored the therapeutic potential of human mesenchymal stroma-/stem-like cells (MSC)-derived exosomes to reduce progressive growth-arrest and senescence in high passages of MSC primary cultures and, to combat cellular senescence in kidney tubular cells
25 kDa CD81 in all of the investigated samples (Figure 1). These findings demonstrated that all three MSC populations produce and release extracellular vehicles (EVs) that display the size and morphology and simultaneously carry the tetraspanin molecules typical for exosomes
Summary
Challenges of age-associated diseases are steadily growing and pose an enormous burden to public health. Aging of the kidney is characterized by a gradual loss of resistance to stress and a decreased capacity to repair, leading to a dramatically increased prevalence of chronic kidney disease (CKD) among the elderly [1]. Cellular senescence is a specialized cell state of permanent cell cycle arrest caused by the accumulation of cellular damage due to a variety of stressors, such as telomere shortening, DNA damage, oxidative stress, and activation of oncoproteins [7,8,9]. Senescent cells interfere with the functionality of tissues and organs due to their inability to divide, an accompanying loss of specialized functions and the secretion of active biomolecules, which trigger inflammation and cell dysfunction, summarized as the senescence-associated secretory phenotype (SASP) [10]
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