Neonatal bladder-derived mesenchymal stem cells ameliorate bladder dysfunction in diabetic rat models

Purpose: To evaluate the effect of a new mesenchymal stem cell type derived from the neonatal bladder (nMSC-B) on diabetic bladder dysfunction (DBD). Materials and Methods: nMSC-B were harvested from neonatal male Sprague-Dawley rat’s bladder and expand- ed in culture. nMSC-B were transferred to Type-1 diabetic rats which were induced by a single dose 45 mg/kg Streptozocin (STZ). Stem cells were transferred via intraperitoneally (IP) (DM-IP group, n:6) and by direct injec- tion to the detrusor (DM-D group, n:6) at 12th week following diabetes and compared with Phosphate Buffered Saline (PBS) injected diabetic rats (DM-PBS group, n:6) and age-matched PBS injected non-diabetic normal rats (NR-PBS group, n:6). All rats were evaluated histopathologically and functionally four weeks after the stem cell treatment. Results: nMSC-B showed improvement in both voiding function and bladder structure. The maximum voiding pressure (MVP) values in the DM-PBS group were lower compare to DM-IP, DM-D and NR-PBS groups (13.27 ± 0.78 vs 16.27 ± 0.61, 28.59 ± 2.09, 21.54 ± 1.00, respectively, P < .001). There was a significant improvement for MVP values in stem cell-treated groups. Immunohistochemical examination revealed decreased bladder smooth muscle (SM), increased fibrosis and desquamation in urothelia in diabetic groups compared to normal group(P < .001). We detected recovery in the stem cell groups. This recovery was more evident in DM-D group. No statisti- cal difference was observed in SM and fibrosis between DM-D and NR-PBS groups (P = .9). Conclusion: It was shown that nMSCBs provided amelioration of DBD. We think that nMSC-B constitutes an effective treatment method in DBD

Nonclassical Congenital Adrenal Hyperplasia and Pregnancy

Objective. The most common form of congenital adrenal hyperplasia (CAH) is 21-hydroxylase (21-OH) deficiency due to mutation of the CYP21A2 gene. Patients with nonclassical CAH (NC-CAH) are usually asymptomatic at birth and typically present in late childhood, adolescence, or adulthood with symptoms of excessive androgen secretion. Subfertility is relative in NC-CAH, but the incidence of spontaneous miscarriage is higher. Here, we report a previously undiagnosed female who gave birth to a normal male child and is planning to become pregnant again. Case Report. A 32-year-old female was referred to our clinic for obesity. Her medical history revealed that she had had three pregnancies. She was planning to become pregnant again. Her laboratory results revealed that she had NC-CAH. Since her husband is the son of her aunt and she had miscarriages and intrauterin exitus in her history, their genetic analyses were performed. Conclusion. Since most patients with NC-CAH have a severe mutation, these patients may give birth to a child with the classical CAH (C-CAH) if their partner is also carrying a severe mutation. Females with NC-CAH who desire pregnancy must be aware of the risk of having an infant with C-CAH

Determination of the effects of bone marrow derived mesenchymal stem cells and ovarian stromal stem cells on follicular maturation in cyclophosphamide induced ovarian failure in rats

Objective: Chemotherapy causes depletion of primordial follicles that leads to premature ovarian failure in female cancer survivals. We investigated the effect of bone marrow derived mesenchymal (BMMSCs) and ovarian stromal stem cells (OSSCs) on follicle maturation in chemotherapy induced ovarian failure. Material and methods: Thirty six Wistar Albino female rats were divided into three groups. Cyclophosphamide at a dose of 200 mg/kg was intraperitoneally (IP) given to the rats in all groups two times. 4 × 106 BMMSCs (IP) was injected to the group-2 and 4 × 106 OSSCs (IP) was injected to the group-3. Serum Anti-Müllerian Hormone (AMH) levels was determined with ELISA and primordial follicles were counted for investigation of primordial follicle reserve. The ovarian structure were evaluated histomorphologically. Localization of BrdU labeled stem cells, the expression of the cell cycle regulator p34Cdc2, gap junction protein p-connexin43 and intraovarian regulators of folliculogenesis Bone Morphogenic Protein 6 and 15 (BMP-6 and BMP-15) were investigated by immunohistochemistry. Results: The immunstaining of BMP-6 was higher in oocytes of group-3 more than group-1 and group-2. The immunpositivity of p34cdc2 and BMP-15 were also higher in follicular cells of group-3 than the other groups. The presence of p-connexin43 in group-3 was determined more than group-1 and group-2. The ovarian follicles with normal histological structure were observed just in group-3. Although, The AMH levels were decreased in rats from all groups at the end of experimental procedure the primordial follicle counts in group-3 was significantly higher than group-1. Conclusion: Our findings suggest that OSSCs have more protective effect on follicle maturation than BMMSCs in cyclophosphamide induced ovarian damage. Keywords: Cyclophosphamide, Ovary, Ovarian follicle, Stem cell

Keratinocyte growth factor-2 and autologous serum potentiate the regenerative effect of mesenchymal stem cells in cornea damage in rats

AIM:To investigate the healing process after severe corneal epithelial damage in rats treated with mesenchymal stem cells (MSCs) cultured with or without keratinocyte growth factor (KGF-2) and autologous serum (AS) on amniotic membrane (AM). Many patients are blind and devastated by severe ocular surface diseases due to limbal stem cell deficiency. Bone marrow-derived MSCs are potential sources for cell-based tissue engineering to repair or replace the corneal tissue, having the potential to differentiate to epithelial cells.METHODS:The study included 5 groups each including 10 female “Sprague Dawley” rats in addition to 20 male rats used as bone marrow donors. Group I rats received AM+MSCs, Group II rats AM+MSCs cultured with KGF-2, Group III rats AM+MSCs cultured with KGF-2+AS, Group IV rats only AM and Group V rats, none. AS was derived from blood drawn from male rats and bone marrow was obtained from the femur and tibia bones of the same animals. Therapeutic effect was evaluated with clinical, histopathological and immunohistochemical assessment. MSC engraftment was demonstrated via detection of donor genotype (Y+) in the recipient tissue (X) with polymerase chain reaction.RESULTS:Corneal healing was significantly better in Groups I-III rats treated with MSC transplantation compared to Group IV and Group V rats with supportive treatment only. The best results were obtained in Group III rats with 90% transparency, 70% lack of neovascularization, and 100% epithelium damage limited to less than 1/4 of cornea.CONCLUSION: We suggest that culture of MSCs with KGF-2 and AS on AM is effective in corneal repair in case of irreversible damage to limbal stem cells

Efficacy Of Topical Mesenchymal Stem Cell Therapy In The Treatment Of Experimental Dry Eye Syndrome Model

Purpose. The current study was set out to address the therapeutic efficacy of topically applied mesenchymal stem cells (MSCs) on dry eye syndrome (DES) induced by benzalkonium chloride (BAC) in rats. Methods. Rats were divided into two groups just after establishment of DES. Eye drops containing either bromodeoxyuridine labeled MSCs (n = 9) or phosphate buffer solution (n = 7) were topically applied once daily for one week. Schirmer test, break-up time score, ocular surface evaluation tests, and corneal inflammatory index scoring tests were applied to all rats at baseline and after treatment. All rats were sacrificed after one week for histological and electron microscopic analysis. Results. Mean aqueous tear volume and tear film stability were significantly increased in rats treated with MSCs (P < 0.05). Infiltration of bromodeoxyuridine labeled MSCs into the meibomian glands and conjunctival epithelium was observed in MSCs treated rats. Increased number of secretory granules and number of goblet cells were observed in MSCs treated rats. Conclusion. Topical application of MSCs could be a safe and effective method for the treatment of DES and could potentially be used for further clinical research studies.PubMedWoSScopu