Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into many lineages. Although the growing interest in BM-MSCs has led to a number of characterization studies, some important biochemical and immunohistochemical properties are still lacking. In this study, morphological and immunophenotypic properties of BM-MSCs were examined in detail. Differentiation potential and growth kinetics of adult rat BM-MSCs were also determined. Immunohistochemistry and RT-PCR results indicated that BM-MSCs expressed myogenic (desmin, myogenin, myosin IIa, and alpha-SMA), neurogenic (gamma-enolase, MAP2a,b, c-fos, nestin, GFAP and beta III tubulin), and osteogenic (osteonectin, osteocalcin, osteopontin, Runx-2, BMP-2, BMP-4 and type I collagen) markers without stimulation towards differentiation. These expression patterns indicated why these cells can easily differentiate into multiple lineages both in vitro and in vivo. Ultrastructural characteristics of rBM-MSCs showed more developed and metabolically active cells.
Dental pulp stem cells (hDP-SCs) were primarily derived from pulp tissues of primary incisors, exfoliated deciduous and permanent third molar teeth. To understand the characteristics of hDP-SCs from impacted third molar, proliferation capacities, gene expression profiles, phenotypic, ultrastructural, and differentiation characteristics were analyzed in comparison with human bone marrow-derived mesenchymal stem cells (hBM-MSCs), extensively. hDP-SCs showed more developed and metabolically active cells. Contrary to hBM-MSCs, hDP-SCs strongly expressed both cytokeratin (CK)-18 and -19, which could involve in odontoblast differentiation and dentine repair. The intrinsic neuro-glia characteristics of hDP-MSCs were demonstrated by the expression of several specific transcripts and proteins of neural stem cell and neurons. These cells not only differentiate into adipogenic, osteogenic, and chondrogenic lineage, but also share some special characteristics of expressing some neural stem cell and epithelial markers. Under defined conditions, hDP-SCs are able to differentiate into both neural and vascular endothelial cells in vitro. Dental pulp might provide an alternative source for human MSCs. hDP-SCs with a promising differentiation capacity could be easily isolated, and possible clinical use could be developed for neurodegenerative and oral diseases in the future.
Hereditary defects of coenzyme Q 10 biosynthesis cause steroid-resistant nephrotic syndrome (SRNS) as part of multiorgan involvement but may also contribute to isolated SRNS. Here, we report 26 patients from 12 families with recessive mutations in ADCK4. Mutation detection rate was 1.9% among 534 consecutively screened cases. Patients with ADCK4 mutations showed a largely renal-limited phenotype, with three subjects exhibiting occasional seizures, one subject exhibiting mild mental retardation, and one subject exhibiting retinitis pigmentosa. ADCK4 nephropathy presented during adolescence (median age, 14.1 years) with nephrotic-range proteinuria in 44% of patients and advanced CKD in 46% of patients at time of diagnosis. Renal biopsy specimens uniformly showed FSGS. Whereas 47% and 36% of patients with mutations in WT1 and NPHS2, respectively, progressed to ESRD before 10 years of age, ESRD occurred almost exclusively in the second decade of life in ADCK4 nephropathy. However, CKD progressed much faster during adolescence in ADCK4 than in WT1 and NPHS2 nephropathy, resulting in similar cumulative ESRD rates (.85% for each disorder) in the third decade of life. In conclusion, ADCK4-related glomerulopathy is an important novel differential diagnosis in adolescents with SRNS/FSGS and/or CKD of unknown origin.
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.
Epidermal growth factor (EGF) modulates Leydig cell proliferation, steroidogenesis, spermiogenesis, and Sertoli cell activity. It plays an important role in repairing ischemia-reperfusion injury in different tissues. The aim of this study was to evaluate the effects of sustained and local administration of EGF on improving bilateral testicular tissue after torsion. A total of 57 Wistar albino rats were used. For the EGF transport system, 1x2 cm gelatin films containing 2 microg EGF were used. Torsion was created by rotating the right testis 720 degrees in a clockwise direction for 4 h in all groups except the control group. Then, in the torsion group, bilateral orchiectomy was performed. After returning the torsioned ipsilateral testes to their normal state, the bilateral testes were wrapped by 1x2 cm unloaded gelatin films in the gelatin (G7 and G21) groups and, by 2 microg EGF loaded gelatin films in the EGF 7 and EGF 21 groups. The testes were removed on the seventh and 21st days, respectively, for biochemical and histological examination. Histologically, Johnsen's spermatogenesis criteria and mean seminiferous tubule diameter (MSTD) measurements were used. The EGF7 group did not show significant loss of Sertoli cells, while in the G7 group the number of these cells decreased. The ipsilateral ischemic testis of the EGF21 group showed Leydig cell hyperplasia, and the contralateral non-ischemic testes in this group were similar to the control group. In the G21 group, the bilateral testes showed Sertoli cell only syndrome in some sections, and most of the cells were undergoing apoptosis. The mean spermatogenesis scores and MSTD in the EGF7 and EGF21 groups were higher than in the G7 and G21 groups ( P<0.05). Malondialdehyde levels were significantly lower in the EGF groups than in the G groups ( P<0.05). Glutathione peroxidase (GSH-Px) levels in the G21 group were significantly higher than in the EGF21 group. Our study shows that local and sustained EGF release after testicular torsion improves bilateral testicular injury. EGF administration may be a new treatment choice for bilaterally injured testis after detorsion without removing the twisted testis.
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