Human amniotic fluid stem cell therapy can help regain bladder function in type 2 diabetic rats

BACKGROUND Diabetes mellitus(DM)is a serious and growing global health burden.It is estimated that 80%of diabetic patients have micturition problems such as poor emptying,urinary incontinence,urgency,and urgency incontinence.Patients with diabetic bladder dysfunction are often resistant to currently available therapies.It is necessary to develop new and effective treatment methods.AIM To examine the therapeutic effect of human amniotic fluid stem cells(hAFSCs)therapy on bladder dysfunction in a type 2 diabetic rat model.METHODS Sixty female Sprague-Dawley rats were divided into five groups:Group 1,normal-diet control(control);group 2,high-fat diet(HFD);group 3,HFD plus streptozotocin-induced DM(DM);group 4,DM plus insulin treatment(DM+insulin);group 5,DM plus hAFSCs injection via tail vein(DM+hAFSCs).Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure,voided volume,intercontraction interval,bladder capacity,and residual volume.Immunoreactivities and/or mRNA expression of muscarinic receptors,nerve growth factor(NGF),and sensory nerve markers in the bladder and insulin,MafA,and pancreatic-duodenal homeobox-1(PDX-1)in pancreatic beta cells were studied.RESULTS Compared with DM rats,insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume,intercontraction interval,bladder capacity,and residual volume(P<0.05).However,both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls(P>0.05).The immunoreactivities and mRNA expression of M2-and M3-muscarinic receptors(M2 and M3)were increased mainly at 4 wk(P<0.05),while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF,calcitonin gene-related peptide(CGRP),substance P,insulin,MafA,and PDX-1 were decreased in DM rats(P<0.05).However,insulin and hAFSCs treatment could help to regain the expression of M2,M3,NGF,CGRP,substance P,MafA,and PDX-1 to near the levels of controls at 4 and/or 12 wk(P>0.05).CONCLUSION Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM;however,hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.