Current Bioengineering Methods for Whole Kidney Regeneration

Kidney regeneration is likely to provide an inexhaustible source of tissues and organs for immunosuppression-free transplantation. It is currently garnering considerable attention and might replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, anatomical complications make kidney regeneration difficult. Here, we review recent advances in the field of kidney regeneration, including (i) the directed differentiation of induced pluripotent stem cells/embryonic stem cells into kidney cells; (ii) blastocyst decomplementation; (iii) use of a decellularized cadaveric scaffold; (iv) embryonic organ transplantation; and (v) use of a nephrogenic niche for growing xenoembryos for de novo kidney regeneration from stem cells. All these approaches represent potentially promising therapeutic strategies for the treatment of patients with chronic kidney disease. Although many obstacles to kidney regeneration remain, we hope that innovative strategies and reliable research will ultimately allow the restoration of renal function in patients with end-stage kidney disease

De Novo Kidney Regeneration with Stem Cells

Recent studies have reported on techniques to mobilize and activate endogenous stem-cells in injured kidneys or to introduce exogenous stem cells for tissue repair. Despite many recent advantages in renal regenerative therapy, chronic kidney disease (CKD) remains a major cause of morbidity and mortality and the number of CKD patients has been increasing. When the sophisticated structure of the kidneys is totally disrupted by end stage renal disease (ESRD), traditional stem cell-based therapy is unable to completely regenerate the damaged tissue. This suggests that whole organ regeneration may be a promising therapeutic approach to alleviate patients with uncured CKD. We summarize here the potential of stem-cell-based therapy for injured tissue repair and de novo whole kidney regeneration. In addition, we describe the hurdles that must be overcome and possible applications of this approach in kidney regeneration

Influence of Repeated Odor Adaptation Experience on the Olfactory Response

Recent studies have reported that essential oils and fragrances sprayed indoors affect psychologica evaluation and intellectual productivity. However, the effects of long-term exposure to fragrances on the human body have not been well studied, and there are still many unresolved issues. Therefore, in this study, the effects of repeated exposure to fragrances on changes in the perception of fragrances as a study for long-term operation of fragrance environments were investigated. In order to investigate the effect of fragrance repetition on threshold and odor perception, a panel experiment with 19 subjects was conducted using rosemary essential oil and scatole. The Rosemary was be exposed and the Scatole was not. The conditions were repetition frequency of adaptation. Regarding thresholds, several panels showed an increase in thresholds for rosemary with exposure and a decrease in thresholds for scatole, indicating a long-term acclimation trend due to repeated exposure to fragrances. As for the subjective evaluation of fragrance, the evaluation of fragrance preference and pleasantness/ unpleasantness tended to change to the neutral side in the case of lower frequency and longer duration. In the future, experiments that tend to increase the number of conditions of the frequencies and duration of repeated exposure will be conducted

Correction: Adipose Tissue-Derived Mesenchymal Stem Cells in Long-Term Dialysis Patients Display Downregulation of PCAF Expression and Poor Angiogenesis Activation.

[This corrects the article DOI: 10.1371/journal.pone.0102311.]

Adipose tissue-derived mesenchymal stem cells in long-term dialysis patients display downregulation of PCAF expression and poor angiogenesis activation.

We previously demonstrated that mesenchymal stem cells (MSCs) differentiate into functional kidney cells capable of urine and erythropoietin production, indicating that they may be used for kidney regeneration. However, the viability of MSCs from dialysis patients may be affected under uremic conditions. In this study, we isolated MSCs from the adipose tissues of end-stage kidney disease (ESKD) patients undergoing long-term dialysis (KD-MSCs; mean: 72.3 months) and from healthy controls (HC-MSCs) to compare their viability. KD-MSCs and HC-MSCs were assessed for their proliferation potential, senescence, and differentiation capacities into adipocytes, osteoblasts, and chondrocytes. Gene expression of stem cell-specific transcription factors was analyzed by PCR array and confirmed by western blot analysis at the protein level. No significant differences of proliferation potential, senescence, or differentiation capacity were observed between KD-MSCs and HC-MSCs. However, gene and protein expression of p300/CBP-associated factor (PCAF) was significantly suppressed in KD-MSCs. Because PCAF is a histone acetyltransferase that mediates regulation of hypoxia-inducible factor-1α (HIF-1α), we examined the hypoxic response in MSCs. HC-MSCs but not KD-MSCs showed upregulation of PCAF protein expression under hypoxia. Similarly, HIF-1α and vascular endothelial growth factor (VEGF) expression did not increase under hypoxia in KD-MSCs but did so in HC-MSCs. Additionally, a directed in vivo angiogenesis assay revealed a decrease in angiogenesis activation of KD-MSCs. In conclusion, long-term uremia leads to persistent and systematic downregulation of PCAF gene and protein expression and poor angiogenesis activation of MSCs from patients with ESKD. Furthermore, PCAF, HIF-1α, and VEGF expression were not upregulated by hypoxic stimulation of KD-MSCs. These results suggest that the hypoxic response may be blunted in MSCs from ESKD patients

Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway in C. elegans.

Electrical current at physiological strength has been applied as a therapeutic approach for various diseases. Several of our works showed that mild electrical stimulation (MES) at 0.1-ms pulse width has positive impact on organisms. But despite the growing evidence of the beneficial effects of MES, its effects on individual animals and the molecular underpinnings are poorly understood and rarely studied. Here, we examined the effects of MES on individual animal and its mechanisms by mainly using Caenorhabditis elegans, a powerful genetic model organism. Interestingly, MES increased stress resistance and suppressed excess fat accumulation in wild-type N2 worms but not in AMPK/AAK-2 and LKB1/PAR-4 mutant worms. MES promoted the nuclear localization of transcription factors DAF-16 and SKN-1 and consequently increased the expression of anti-stress genes, whereas MES inhibited the nuclear localization of SBP-1 and suppressed the expression of lipogenic genes. Moreover, we found that MES induced the activation of LKB1/PAR4-AMPK/AAK2 pathway in C. elegans and in several mammalian cell lines. The mitochondrial membrane potential and cellular ATP level were slightly and transiently decreased by MES leading to the activation of LKB1-AMPK signaling pathway. Together, we firstly and genetically demonstrated that MES exerts beneficial effects such as stress resistance and suppression of excess fat accumulation, via activation of LKB1-AMPK signaling pathway