Adipose-Derived and Bone Marrow Stem Cell Exosomes Assist in Human Kidney Cell Immunomodulation
DeVito, Dana T.
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Every year 13.3 million individuals suffer from acute kidney injury (AKI) which often causes the development of chronic kidney disease (CKD). Of those diagnosed with CKD, fifty percent experience increased fibrosis and progress into terminal end stage renal disease (ESRD). The use of mesenchymal stem cells (MSCs) to aid in renal recovery and survival post-AKI has changed the way we view treatments of renal fibrosis and subsequent ESRD. Of the various MSC treatments, the MSC microvesicle (MV) and exosome treatments have recently increased in popularity since their paracrine characteristics bypass complications inflicted on cells when directly injected with MSCs. While it is believed that MSC exosomes can regulate inflammation, some literature remains skeptical of their benefits compared to their risks. The immunomodulatory effects of bone marrow (BM) and adipose-derived (AD) stem cell exosomes were investigated by measuring the presence of common reno-destructive biomarkers including fibrotic growth factor-2 (FGF-2) and Collagen-I, and reno-protective biomarkers including bone morphogenic protein-7 (BMP-7), and receptor protein CD63. FGF-2 ELISAs showed that FGF-2 may not accurately represent the level of fibrosis in immortal human kidney tubular epithelial (HK-2) cells as previously represented in literature. Collagen-I ELISAs demonstrated harmful effects from both AD and BM exosome treatments. Western blot analysis confirmed that exosomes can supply reno-protective BMP-7 and CD63. Cytokine and chemokine arrays further showed that AD and BM exosome and fibrosis-inducing TGF-β1 treatments provide cells with different paracrine factors. Results showed that AD and BM exosomes are capable of immunomodulation in HK-2 cells; however, further studies should be conducted to determine if they can successfully be used as a treatment for renal fibrosis by countering reno-destruction and therefore prevent ESRD.