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

Abstract

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.

Human amniotic fluid stem cells can alleviate detrusor dysfunction caused by bladder outlet obstruction in rats

“…Fourth, the present study did not examine the presence of immunosuppression. However, our previous data have revealed that the hAFSCs injection in animal studies was not found to develop any immune rejection against transplanted tissue 13 – 15 , 17 , 42 .…”

“…Interim analysis up to 12 months showed encouraging improvement in bladder function, and no serious treatment-related adverse effects occurred. Since hAFSCs can be obtained from amniotic fluid, grow easily in culture and appear phenotypically and genetically stable, our and previous studies have suggested hAFSCs can act as a novel source for cell transplantation therapy better than other adult stem cells 12 – 15 , 17 , 42 .…”

“…All the cystometric parameters on 5 consecutive micturition cycles were collected for analysis. Three cystometric variables were investigated including peak voiding pressure, bladder capacity and residual volume 17 . Cystometry Analysis Version 1.05 (Catamount Research and Development, St Albans, VT, USA) was used for cystometric analysis.…”

Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat

“…The reason why we used 1 × 10 6 mouse iPSCs but not higher concentration is based on our previous studies. We found that the concentration of 1 × 10 6 was effective for human amniotic fluid stem cell transplantation on bladder function in many different animal models including rat models with diabetes [ 23 ], spinal cord injury [ 24 ], atherosclerosis-induced chronic bladder ischemia [ 64 ], middle cerebral artery occlusion [ 25 ] and pelvic nerve transection [ 65 ]. However, it is possible that higher concentration may have better thrombolytic effect when added to 0.45 mg/kg rt-PA after LED irradiation.…”

“…First, we used only single injection of iPSCs and it is possible that multiple injections may give better effect. However, single injection is the most convenient way of treatment in clinical settings, and our previous studies [ 23 – 25 , 64 , 65 ] all used single injection of stem cell and had obtained good effect. Second, since the present study was designed based on clinical scenario, we did not examine the detailed mechanism as to how iPSCs can improve thrombolytic effect.…”