IntroductionThe prevalence of renal fibrosis is higher in older than in younger individuals. Through paracrine activity, bone marrow mesenchymal stem cell-derived microvesicles (BM-MSC-MVs) influence the process of renal fibrosis. Differences in microRNA (miRNA) expression of BM-MSC-MVs that correlate with the age of the subjects and the correlation between miRNA expression and the process of renal fibrosis have not been established. The present study aimed to analyze differences in miRNA expression of BM-MSC-MVs between young or older rats and its influence on tumor growth factor-beta 1 (TGF-β1)-mediated epithelial-mesenchymal transition (EMT) of HK2 cells to explore the causes of renal fibrosis in aged tissues.MethodsmiRCURY LNA Array (version 18.0) was used to identify differentially expressed miRNAs in BM-MSC-MVs of 3- and 24-month-old Fisher344 rats. Reverse transcription-polymerase chain reaction was used to verify miRNA levels in BM-MSC-MVs and in the serum of rats. A TGF-β1-mediated EMT model was used to study the effects of BM-MSC-MVs and differentially expressed miRNAs on EMT.ResultsBM-MSCs from older rats showed more severe aging phenotypes compared with those of young rats. In addition, the growth rate and cell migration of BM-MSCs derived from older rats were significantly reduced. In secreted BM-MSC-MVs, the expression of miR-344a, miR-133b-3p, miR-294, miR-423-3p, and miR-872-3p was significantly downregulated in older rats than in younger rats (P < 0.05), and the serum level of these miRNAs exhibited the same patterns. Intervention using BM-MSC-MVs resulted in the weakening of TGF-β1-mediated EMT in the aged rats. MiR-344a, miR-133b-3p, and miR-294 affected TGF-β1-mediated EMT in HK2 cells. Among these, miR-133b-3p and miR-294 significantly inhibited TGF-β1-mediated EMT in HK2 cells (P < 0.05).ConclusionsIn older rats, the inhibitory effect of BM-MSC-MVs on TGF-β1-mediated HK2 cell EMT was weaker than that observed in younger rats. In addition, miR-133b-3p and miR-294, which were downregulated in BM-MSC-MVs of older rats, remarkably inhibited TGF-β1-mediated EMT in HK2 cells, suggesting that these may play a role in the fibrosis of aging renal tissues.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0179-x) contains supplementary material, which is available to authorized users.

Stem cells including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and adult stem cells (ASCs) are able to repair/replace damaged or degenerative tissues and improve functional recovery in experimental model and clinical trials. However, there are still many limitations and unresolved problems regarding stem cell therapy in terms of ethical barriers, immune rejection, tumorigenicity, and cell sources. By reviewing recent literatures and our related works, human amnion-derived stem cells (hADSCs) including human amniotic mesenchymal stem cells (hAMSCs) and human amniotic epithelial stem cells (hAESCs) have shown considerable advantages over other stem cells. In this review, we first described the biological characteristics and advantages of hADSCs, especially for their high pluripotency and immunomodulatory effects. Then, we summarized the therapeutic applications and recent progresses of hADSCs in treating various diseases for preclinical research and clinical trials. In addition, the possible mechanisms and the challenges of hADSCs applications have been also discussed. Finally, we highlighted the properties of hADSCs as a promising source of stem cells for cell therapy and regenerative medicine and pointed out the perspectives for the directions of hADSCs applications clinically.

The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia–reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2′-deoxyuridine (EdU)-positive proximal tubular epithelial cells. GDF11 improved the renal repair, recovery of renal function, and survival of elderly mice at 72 h after IRI. Moreover, the addition of recombinant GDF11 to primary renal epithelial cells increased proliferation, migration, and dedifferentiation by upregulating the ERK1/2 pathway in vitro. Our study indicates that GDF11/8 in the kidney decreases with age and that GDF11 can increase tubular cell dedifferentiation and proliferation as well as improve tubular regeneration after acute kidney injury (AKI) in old mice.

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Whether changes in internal body environment affect kidney aging remains unclear. Specifically, it is unknown whether transplanted kidneys from older donors recover from tissue damage after placement in younger recipients. In this study, a parabiosis animal model was established to investigate the effects of a young internal body environment on aged kidneys. The animals were divided into six groups: young (Ycon) and old control (Ocon) groups, isochronic youth-youth group (Y-IP), elderly-elderly group (O-IP), and heterochronic youth (Y-HP) and elderly (O-HP) groups. After parabiosis, tubule and interstitial tissue scores in the O-HP group were significantly lower than in the Ocon and O-IP groups. The expression of aging-related protein p16 and SA-β-gal in the O-HP group was significantly reduced compared with the Ocon and O-IP groups. Autophagy factors Atg5 and LC3BII were significantly upregulated, whereas the expression of the autophagic degradation marker (P62) was significantly downregulated in the O-HP group compared with the Ocon and O-IP groups. With the same comparison, the positive cells of TUNEL staining and the expression of IL-6 and IL-1β were significantly reduced, whereas the total/cleaved caspase-3 and total/pNF-κB were significantly increased in the O-HP group. The results demonstrated that a young blood environment significantly reduces kidney aging. These findings provide new evidence supporting an increase in the upper age limit for human kidney transplantation donors.