ABSTRACT
Objective@#The heart contains a pool of c-kit+ progenitor cells which is believed to be able to regenerate. The differentiation of these progenitor cells is reliant on different physiological cues. Unraveling the underlying signals to direct differentiation of progenitor cells will be beneficial in controlling progenitor cell fate. In this regard, the role of the mitochondria in mediating cardiac progenitor cell fate remains unclear. Specifically, the association between changes in mitochondrial morphology with the differentiation status of c-kit+ CPCs remains elusive. In this study, we investigated the relationship between mitochondrial morphology and the differentiation status of c-kit+ progenitor cells. @*Methods@#and Results: c-kit+ CPCs were isolated from 2-month-old male wild-type FVB mice. To activate differentiation, CPCs were incubated in α-minimal essential medium containing 10 nM dexamethasone for up to 7 days. To inhibit Drp1-mediated mitochondrial fragmentation, either 10 μM or 50 μM mdivi-1 was administered once at Day 0 and again at Day 2 of differentiation. To inhibit calcineurin, either 1 μM or 5 μM ciclosporin-A (CsA) was administered once at Day 0 and again at Day 2 of differentiation. Dexamethasone-induced differentiation of c-kit+ progenitor cells is aligned with fragmentation of the mitochondria via a calcineurin-Drp1 pathway. Pharmacologically inhibiting mitochondrial fragmentation retains the undifferentiated state of the c-kit+ progenitor cells. @*Conclusions@#The findings from this study provide an alternative view of the role of mitochondrial fusion-fission in the differentiation of cardiac progenitor cells and the potential of pharmacologically manipulating the mitochondria to direct progenitor cell fate.
ABSTRACT
Introduction The aim of the study was to compare the clinical and patient-reported outcomes among open pyeloplasty (OP) and laparoscopic pyeloplasty (LP) patients. Materials and methods This was a prospective single centre, case-cohort study conducted in a tertiary care hospital with 62 patients. In both techniques, dismembered Anderson-Hynes pyeloplasty were undertaken. Post-operatively patients underwent visual analogue scale (VAS) assessment for pain, days to ambulation and comparison of the short- and long-term outcomes of the two procedures. Results There was no difference in the physical and functional outcomes between the two surgical approaches at 12 months period after surgery. However, patients in the laparoscopic group did report a higher rate of satisfaction at six weeks and six months' postoperatively. Likewise, patients in LP experienced less pain during the postoperative period (p-value <0.001), with decreased analgesic requirements. This translated into an early patient ambulation in the laparoscopic group (p-value <0.001), and a shorter hospital stay for the LP group (p-value <0.001). Moreover, follow-up ultrasound showed equal improvement of hydronephrosis among the two groups. Conclusion Laparoscopic and open pyeloplasty are equally effective in treating pelvic ureteric junction obstruction (PUJO), with comparable patient-reported outcomes at 12-month follow-up. However, the laparoscopic technique merits over open surgery with faster rehabilitation, a decreased postoperative pain experience and shorter hospital stay.
