Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats.

The effects of human amniotic fluid stem cell (hAFSC) transplantation on bladder function and molecular changes in spinal cord-injured (SCI) rats were investigated. Four groups were studied: sham and SCI plus phosphate-buffered saline (SCI + PBS), human embryonic kidney 293 (HEK293) cells, and hAFSCs transplantation. In SCI + PBS rat bladders, cystometry showed increased peak voiding pressure, voiding volume, bladder capacity, residual volume, and number of non-voiding contractions, and the total elastin/collagen amount was increased but collagen concentration was decreased at days 7 and 28. Immunoreactivity and mRNA levels of IGF-1, TGF-ß1, and ß3-adrenoceptor were increased at days 7 and/or 28. M2 immunoreactivity and M3 mRNA levels of muscarinic receptor were increased at day 7. M2 immunoreactivity was increased, but M2/M3 mRNA and M3 immunoreactivity levels were decreased at day 28. Brain derived-neurotrophic factor mRNA was increased, but immunoreactivity was decreased at day 7. HEK293 cell transplantation caused no difference compared to SCI + PBS group. hAFSCs co-localized with neural cell markers and expressed BDNF, TGF-ß1, GFAP, and IL-6. The present results showed that SCI bladders released IGF-1 and TGF-ß1 to stimulate elastin and collagen for bladder wall remodelling, and hAFSC transplantation improved these changes, which involved the mechanisms of BDNF, muscarinic receptors, and ß3-adrenoceptor expression.

Amniotic Fluid Stem Cells Improve Rat Bladder Dysfunction After Pelvic Nerve Transection.

The effects of human amniotic fluid stem cells (hAFSCs) transplantation on bladder dysfunction after pelvic nerve transection (PNT) remain to be clarified. Five groups of female Sprague-Dawley rats were studied including sham operation, unilateral PNT alone or plus hAFSCs transplantation, and bilateral PNT alone or plus hAFSCs transplantation. hAFSCs were injected at the site of PNT. Cystometries, neurofilament density within bladder nerves, and the expressions of bladder protein gene-product 9.5 (PGP9.5), growth-associated protein 43 (GAP-43), nerve growth factor (NGF), p75 (NGF receptor), CXCL12, CCL7, and enkephalin were studied. Compared to sham-operation group, bladder weight increased and neurofilament density decreased at 10 and 28 days after unilateral and bilateral PNT, but all improved after hAFSCs transplantation. Unilateral PNT could increase bladder capacity, residual volume, and number of nonvoiding contractions but decrease peak voiding pressure and leak point pressure. Bilateral PNT caused overflow incontinence and increased the number of nonvoiding contractions. These cystometric parameters improved after hAFSCs transplantation. After PNT, bladder PGP9.5 mRNA and immunoreactivities decreased at 10 and 28 days, GAP-43 mRNA and immunoreactivities increased at 10 days and decreased at 28 days, both NGF and p75 mRNAs and immunoreactivities increased at 10 and/or 28 days, and enkephalin immunoreactivities decreased at 10 and 28 days, but these were all improved after hAFSCs transplantation. Our results showed that bladder dysfunction induced by PNT could be improved by hAFSCs transplantation, and PGP9.5, GAP-43, and neurotrophins could be involved in the mechanisms of nerve regeneration after hAFSCs transplantation.

Detection of fetal trisomy 9 mosaicism by noninvasive prenatal testing through maternal plasma DNA sequencing.

OBJECTIVE: Noninvasive prenatal testing (NIPT) is widely used as a powerful screening tool to detect common aneuploidies. However, its application for detection of rare chromosomal abnormalities remains inconclusive. CASE REPORT: A 38-year-old woman (gravida 2, para 0) requested NIPT as a primary screening test for fetal aneuploidies at 13 weeks and 1 day of gestation. An unexpected Trisomy 9 (T9) abnormality was highly suspected. Amniocentesis was arranged for further diagnosis at 18 weeks of gestation. Final karyotyping reported 47,XX,+9 [18]/46,XX [12], indicating 60% T9 mosaicism. CONCLUSION: This case shows strong evidence that NIPT can be a powerful screening tool to detect rare fetal trisomies at very early gestation.

Improvement in bladder dysfunction after bladder transplantation of amniotic fluid stem cells in diabetic rats.

To examine the effects of human amniotic fluid stem cells (hAFSCs) transplantation on bladder function and molecular changes in diabetic rats, 60 female Sprague-Dawley rats were used for study. Three groups were assigned including sham control rats, streptozotocin (STZ, 60 mg/kg)-induced diabetic rats and STZ-induced diabetic rats plus bladder hAFSCs transplantation. Compared to controls, diabetic rats had decreased body weight but increased bladder weight. Cystometries showed non-voiding contraction, residual volume, voided volume and intercontraction interval increased significantly in diabetic rats at week 4 and 12 after DM induction, but improved after hAFSCs transplantation. The immunoreactivities and mRNAs of nerve growth factor (NGF) decreased significantly in diabetic bladder at week 4 and 12 after DM induction, but recovered after hAFSCs transplantation. The immunoreactivities and mRNAs of M2 and M3 muscarinic receptor increased significantly in diabetic bladder at week 4 after DM induction but recovered after hAFSCs transplantation. The immunoreactivity of 8-hydroxy-20-deoxyguanosine increased significantly in diabetic bladder at week 4 and 12 after DM induction but reduced after hAFSCs transplantation. The present study showed bladder dysfunction in STZ-induced diabetic rats could be improved by hAFSCs transplantation into bladder, which may be related to the recovery of bladder NGF and muscarinic receptors.

Amniotic fluid stem cells ameliorate bladder dysfunction induced by chronic bladder ischemia in rat.

AIMS: This study investigated the protective effect of human amniotic fluid-derived stem cells (hAFSCs) against bladder overactivity in rat model of atherosclerosis-induced chronic bladder ischemia. METHODS: Adult female Sprague-Dawley rats were divided into six groups: (1) Normal control with a regular diet for 8 weeks, (2) Sham-operation, (3) arterial balloon endothelial injury (AEI) of common iliac artery (AEI only), and post-AEI consecutive hAFSCs treatment for (4) 1 day, (5) 3 days, and (6) 7 days. Groups 2-6 were given 2% cholesterol diet for 8 weeks after operation (sham or AEI). Bladder functions were analyzed by cystometry at 8 weeks in controls and after operation in groups 2-6. Wall morphology of common iliac artery was examined by hematoxylin and eosin stain. Bladder oxidative stress and inflammatory markers were studied by immunohistochemistry of 8-hydroxy-2'-deoxyguanosine (8OHdG), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha). RESULTS: Bladder overactivity with decreased voided volumes and intercontraction intervals and increased residual volumes was seen in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days. Compared with controls and shams, the wall thickness of iliac artery was increased in AEI only group, but improved after hAFSCs treatment for 3 and 7 days. The expressions of 8OHdG, MDA, and TNF-alpha were increased in AEI only group, but improved after hAFSCs treatment for 1, 3, and 7 days. CONCLUSIONS: Bladder overactivity caused by chronic bladder ischemia can be improved by hAFSCs treatment, probably by acting through down-regulation of oxidative stress and TNF-alpha expressions.

Corrigendum: In utero therapy for congenital disorders using amniotic fluid stem cells.

[This corrects the article on p. 270 in vol. 5, PMID: 25566071.].