Potential therapeutic effects of long-term stem cells administration: impact on the gene profile and kidney function of PKD/Mhm (Cy/+) rats
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE161093 | GEO | 2022/05/18
REPOSITORIES: GEO
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Project description:Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5+ stromal cells (2 × 106) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5+-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5+ and ASC-treated groups. Additionally, ABCB5+ and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD.
| S-EPMC9102853 | biostudies-literature
Project description:Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cells treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose derived stromal cells (ASC) and human skin-derived ABCB5+ stromal cells (2x106) were monthly, over a period of 6 months, infused intravenously or injected intraperitoneally. Additionally, ASC and ABCB5+ derived conditioned media were administrated intraperitoneally. Gene expression profile results showed a significant reprogramming of metabolism related pathways along with the down-regulation of cAMP, NF-B and apoptosis pathways. During the experimental period, the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device were measured. All together, these analyses show a moderate amelioration of the renal function in ABCB5+ and ASC treated groups. Additionally, ABCB5+ and ASC derived conditioned media treatments lead to milder, but still promising improvements. Cell-based therapy may constitute a novel therapeutic approach in CKD.
2022-05-18 | GSE161092 | GEO
Project description:Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cells treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose derived stromal cells (ASC) and human skin-derived ABCB5+ stromal cells (2x106) were monthly, over a period of 6 months, infused intravenously or injected intraperitoneally. Additionally, ASC and ABCB5+ derived conditioned media were administrated intraperitoneally. Gene expression profile results showed a significant reprogramming of metabolism related pathways along with the down-regulation of cAMP, NF-B and apoptosis pathways. During the experimental period, the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device were measured. All together, these analyses show a moderate amelioration of the renal function in ABCB5+ and ASC treated groups. Additionally, ABCB5+ and ASC derived conditioned media treatments lead to milder, but still promising improvements. Cell-based therapy may constitute a novel therapeutic approach in CKD.
2022-05-18 | GSE161091 | GEO
Project description:Potential therapeutic effects of long-term stem cells administration: impact on the gene profile and kidney function of PKD/Mhm (Cy/+) rats
| PRJNA675548 | ENA
Project description:Potential therapeutic effects of long-term stem cells administration: impact on the gene profile and kidney function of PKD/Mhm (Cy/+) rats [PKD_Dez19]
| PRJNA675552 | ENA
Project description:Potential therapeutic effects of long-term stem cells administration: impact on the gene profile and kidney function of PKD/Mhm (Cy/+) rats [PKD_Jan19]
| PRJNA675553 | ENA
Project description:As the broad spectrum pharmacological action, aspirin has been one of the most widely used medicines since its initial synthesis; however, the association between aspirin and erectile function is still controversial. We aim to explore whether long-term aspirin administration deteriorates or preserves erectile function from adult rats and ageing rat model. Twenty adult rats (10 weeks of age) and twenty ageing rats (80 weeks of age) were randomly divided into four groups as follows: Adult-Control (normal saline [NS]), Adult-Aspirin (aspirin, 10?mg/kg/d), Ageing-Control (NS), and Ageing-Aspirin (aspirin, 10?mg/kg/d) groups (n?=?10 per group). For all rats, erectile function was assessed by maximum intracavernous pressure (ICP), total area under ICP curve (AUC), ICP/mean arterial pressure (MAP) ratio, and MAP. The total treatment duration was one month. Protein expression levels of cyclooxygenase-1 (COX-1), COX-2, endothelial nitric oxide synthase (eNOS), and nNOS of the corpus cavernosum were detected by Western blot. ELISA kits were used to determine 6-keto PGF1a, PGE2, TXB2, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) levels. Total nitric oxide (NO) concentration was measured using a fluorometric assay kit. As a result, Ageing-Control rats revealed significantly decreased ICP, AUC, and ICP/MAP ratios compared to Adult-Control rats, and these effects were accompanied by reduced eNOS protein expression and lower total NO and cGMP levels; however, no difference was found in nNOS protein expression. For adult rat groups, aspirin significantly inhibited the production of 6-keto PGF1a, PGE2, and TXB2; however, it neither changed the ICP, AUC, or ICP/ MAP ratios nor altered the protein expression of eNOS, nNOS, COX-1, and COX-2. Meanwhile, aspirin did not influence the concentrations of total NO, cAMP, or cGMP. The same tendency was also found in the ageing rat model, which confirmed that aspirin did not alter erectile function. Our data suggested that long-term aspirin administration did not strengthen or weaken erectile function in adult rats or ageing rat model. Thus, it had no impact on erectile function.
| S-EPMC6538637 | biostudies-literature
Project description:BACKGROUND AND OBJECTIVES:In the 3-year Tolvaptan Efficacy and Safety in Management of ADPKD and Its Outcomes (TEMPO) 3:4 and 1-year Replicating Evidence of Preserved Renal Function: an Investigation of Tolvaptan Safety and Efficacy in ADPKD (REPRISE) trials, tolvaptan slowed the decline of eGFR in patients with autosomal dominant polycystic kidney disease at early and later stages of CKD, respectively. Our objective was to ascertain whether the reduction associated with the administration of tolvaptan is sustained, cumulative, and likely to delay the need for kidney replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:One hundred and twenty-eight patients with autosomal dominant polycystic kidney disease participated in clinical trials of tolvaptan at the Mayo Clinic. All had the opportunity to enroll into open-label extension studies. Twenty participated in short-term studies or received placebo only. The remaining 108 were analyzed for safety. Ninety seven patients treated with tolvaptan for ?1 year (mean±SD, 4.6±2.8; range, 1.1-11.2) were analyzed for efficacy using three approaches: (1) comparison of eGFR slopes and outcome (33% reduction from baseline eGFR) to controls matched by sex, age, and baseline eGFR; (2) Stability of eGFR slopes with duration of follow-up; and (3) comparison of observed and predicted eGFRs at last follow-up. RESULTS:Patients treated with tolvaptan had lower eGFR slopes from baseline (mean±SD, -2.20±2.18 ml/min per 1.73 m2 per year) and from month 1 (mean±SD, -1.97±2.44 ml/min per 1.73 m2 per year) compared with controls (mean±SD, -3.50±2.09 ml/min per 1.73 m2 per year; P<0.001), and lower risk of a 33% reduction in eGFR (risk ratio, 0.63; 95% confidence interval, 0.38 to 0.98 from baseline; risk ratio, 0.53; 95% confidence interval, 0.31 to 0.85 from month 1). Annualized eGFR slopes of patients treated with tolvaptan did not change during follow-up and differences between observed and predicted eGFRs at last follow-up increased with duration of treatment. CONCLUSIONS:Follow-up for up to 11.2 years (average 4.6 years) showed a sustained reduction in the annual rate of eGFR decline in patients treated with tolvaptan compared with controls and an increasing separation of eGFR values over time between the two groups.
| S-EPMC6086720 | biostudies-literature
Project description:Gender has strong impact on kidney performance. Female gender tends to be renal protective. PKD/Mhm is rat model for human polycystic kidney disease (PKD) caused by a mutation in gene Anks6. PKD progresses faster in male rats compared with females. We used microarrays to detect gender-dependent gene expression in kidney of 36d old PKD/Mhm rats. Keywords: gender, genotype
2009-09-30 | GSE13065 | GEO
Project description:BACKGROUND:The relationship between acute kidney injury (AKI) and long-term renal function is controversial. The influence of AKI duration on functional recovery after partial nephrectomy has never been investigated. OBJECTIVE:To investigate the association between AKI and renal function 1yr after partial nephrectomy, and whether this relationship is affected by the duration of AKI. DESIGN, SETTING, AND PARTICIPANTS:We analyzed the data of 1893 patients treated by partial nephrectomy for a single cT1 N0 M0 renal mass. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:We defined three outcomes of interest: (1) recovery of at least 90% of baseline function 1yr after partial nephrectomy, (2) percentage change of 1-yr renal function compared with baseline function, and (3) chronic kidney disease (CKD) upstaging. AKI was defined according to the RIFLE criteria and recorded up to the 7th postoperative day. The association between AKI and each endpoint of interest was examined using regression models after adjustment for common predictors of renal function. RESULTS AND LIMITATIONS:A total of 388 (20%) patients experienced AKI after surgery. The rate of patients recovering 90% of baseline function was lower in the AKI group (30% vs 61%), while the proportion of patients who had CKD upstaging was significantly higher (51% vs 23%; both p<0.0001). At multivariable analysis, AKI was associated with worse renal function 1yr after partial nephrectomy, regardless of the outcome of interest (all p<0.0001). Longer AKI increases the risk of functional deterioration, especially after the 3rd day of injury. The risk of CKD upstaging for an average patient who had 1-3 versus ?4 d of AKI was 46% (95% confidence interval [CI]: 40%, 52%) versus 67% (95% CI: 55%, 78%; absolute risk increase of 21%; 95% CI: 8%, 34%). CONCLUSIONS:AKI negatively affects long-term functional recovery after partial nephrectomy, and thus, modifiable factors associated with AKI should be identified and corrected preoperatively. The duration of injury is informative, and should be included in the assessment of AKI and in future studies addressing this topic. PATIENT SUMMARY:Proper functional recovery after partial nephrectomy is jeopardized by acute kidney injury (AKI). Inclusion of the dimension of time into classification systems for AKI may be beneficial for postoperative risk stratification.
| S-EPMC7641193 | biostudies-literature