|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | NOS inhibition synchronizes calcium oscillations in human adipose tissue-derived mesenchymal stem cells by increasing gap junctional coupling. J Cell Physiol. 2010 Nov 10; Authors: Sauer H, Sharifpanah F, Hatry M, Steffen P, Bartsch C, Heller R, Padmasekar M, Howaldt HP, Bein G, Wartenberg M Adipose tissue-derived mesenchymal stem cells (ASCs) are a promising stem cell source for cell transplantation. We demonstrate that undifferentiated ASCs display robust oscillations of intracellular calcium [Ca(2+)]i which may be associated with stem cell maintenance since oscillations were absent in endothelial cell differentiation medium supplemented with FGF-2. [Ca(2+)]i oscillations were dependent on extracellular Ca(2+) and Ca(2+) release from intracellular stores since they were abolished in Ca(2+)-free medium and in the presence of the store-depleting agent thapsigargin. They were inhibited by the phospholipase C antagonist U73,122, the InsP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB) as well as by the gap junction uncouplers 1-heptanol and carbenoxolone, indicating regulation by the inositol 1,4,5-trisphosphate (InsP3) pathway and dependence on gap junctional coupling. Cells endogenously generated nitric oxide (NO), expressed NO synthase 1 (NOS 1) and connexin 43 (Cx 43). The nitric oxide NOS inhibitors NG-monomethyl-L-arginine (L-NMMA), N(G)-nitro-L-arginine methyl ester (L-NAME), 2-ethyl-2-thiopseudourea (ETU) and diphenylen iodonium (DPI) as well as si-RNA-mediated downregulation of NOS 1 synchronized [Ca(2+)]i oscillations between individual cells, whereas the NO-donors S-nitroso-N-acetylpenicillamine (SNAP) and sodium nitroprusside (SNP) as well as the soluble guanylate cyclase (sGC) inhibitor 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one (ODQ) were without effects. The synchronization of [Ca(2+)]i oscillations was due to an improvement of intracellular coupling since fluorescence recovery after photobleaching (FRAP) revealed increased reflow of fluorescent calcein into the bleached area in the presence of the NOS inhibitors DPI and L-NAME. In summary our data demonstrate that intracellular NO levels regulate synchronization of [Ca(2+)]i oscillations in undifferentiated ASCs by controlling gap junctional coupling. J. Cell. Physiol. © 2010 Wiley-Liss, Inc. PMID: 21069725 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | EH-myomesin splice isoform is a novel marker for dilated cardiomyopathy. Basic Res Cardiol. 2010 Nov 11; Authors: Schoenauer R, Emmert MY, Felley A, Ehler E, Brokopp C, Weber B, Nemir M, Faggian GG, Pedrazzini T, Falk V, Hoerstrup SP, Agarkova I The M-band is the prominent cytoskeletal structure that cross-links the myosin and titin filaments in the middle of the sarcomere. To investigate M-band alterations in heart disease, we analyzed the expression of its main components, proteins of the myomesin family, in mouse and human cardiomyopathy. Cardiac function was assessed by echocardiography and compared to the expression pattern of myomesins evaluated with RT-PCR, Western blot, and immunofluorescent analysis. Disease progression in transgenic mouse models for dilated cardiomyopathy (DCM) was accompanied by specific M-band alterations. The dominant splice isoform in the embryonic heart, EH-myomesin, was strongly up-regulated in the failing heart and correlated with a decrease in cardiac function (R = -0.86). In addition, we have analyzed the expressions of myomesins in human myocardial biopsies (N = 40) obtained from DCM patients, DCM patients supported by a left ventricular assist device (LVAD), hypertrophic cardiomyopathy (HCM) patients and controls. Quantitative RT-PCR revealed that the EH-myomesin isoform was up-regulated 41-fold (P < 0.001) in the DCM patients compared to control patients. In DCM hearts supported by a LVAD and HCM hearts, the EH-myomesin expression was comparable to controls. Immunofluorescent analyses indicate that EH-myomesin was enhanced in a cell-specific manner, leading to a higher heterogeneity of the myocytes' cytoskeleton through the myocardial wall. We suggest that the up-regulation of EH-myomesin denotes an adaptive remodeling of the sarcomere cytoskeleton in the dilated heart and might serve as a marker for DCM in mouse and human myocardium. PMID: 21069531 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Embryonic stem and haematopoietic progenitor cells resist to Aβ oligomer toxicity and maintain the differentiation potency in culture. Amyloid. 2010 Nov 10; Authors: Neri T, Bucciantini M, Rosti V, Raimondi S, Relini A, Massa M, Zuccotti M, Donadei S, Stefani M, Redi CA, Merlini G, Stoppini M, Garagna S, Bellotti V Regenerative medicine deals with the possible use of stem cells to repair tissues damaged by aging and related diseases, including amyloidoses. In the latter case, the toxicity of the amyloid deposits can, in principle, question the possibility to graft specific tissues by undifferentiated cells. To assess whether stem cells are vulnerable to amyloid toxicity, we exposed, in culture, murine embryonic stem (ES) cells and haematopoietic progenitor (HP) cells to oligomers of the amyloidogenic peptide Aβ42 at concentrations previously shown to be cytotoxic to several other cell types. These stem cells did not display any sign of apoptosis and their survival, proliferation and differentiation were not affected by the oligomers although the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay revealed that ES, but not HP, cells displayed some impaired ability to reduce the tetrazole salts possibly as a result of transient oxidative stress. Our results support a remarkable resistance of the investigated stem cells against amyloids and hence their potential use in cell therapy of Alzheimer's disease and, possibly, other amyloid diseases. PMID: 21067308 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Biomimeticity in tissue engineering scaffolds through synthetic peptide modifications-Altering chemistry for enhanced biological response. J Biomed Mater Res A. 2010 Nov 10; Authors: Sreejalekshmi KG, Nair PD Biomimetic and bioactive biomaterials are desirable as tissue engineering scaffolds by virtue of their capability to mimic natural environments of the extracellular matrix. Biomimeticity has been achieved by the incorporation of synthetic short peptide sequences into suitable materials either by surface modification or by bulk incorporation. Research in this area has identified several novel synthetic peptide segments, some of them with cell-specific interactions, which may serve as potential candidates for use in explicit tissue applications. This review focuses on the developments and prospective directions of incorporating short synthetic peptide sequences onto scaffolds for tissue engineering, with emphasis on the chemistry of peptide immobilization and subsequent cell responses toward modified scaffolds. The article provides a decision-tree-type flow chart indicating the most probable cellular events on a given peptide-modified scaffold along with the consolidated list of synthetic peptide sequences, supports as well as cell types used in various tissue engineering studies, and aims to serve as a quick reference guide to peptide chemists and material scientists interested in the field. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 21069877 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Macrophage and dendritic cell phenotypic diversity in the context of biomaterials. J Biomed Mater Res A. 2010 Nov 10; Authors: Kou PM, Babensee JE Macrophages (Mφ) and dendritic cells (DCs) are critical antigen presenting cells that play pivotal roles in host responses to biomaterial implants. Although Mφs have been widely studied for their roles in the inflammatory responses against biomaterials, the roles that DCs play in the host responses toward implanted materials have only recently been explored. DCs are of significant research interest because of the emergence of a large number of combination products that cross-traditional medical device boundaries. These products combine biomaterials with biologics, including cells, nucleic acids, and/or proteins. The biomaterial component may evoke an inflammatory response, primarily mediated by neutrophils and Mφs, whereas the biologic component may elicit an immunogenic immune response, initiated by DCs involving lymphocyte activation. Control of Mφ phenotypic balance from proinflammatory M1 to reparative M2 is a goal of investigators to optimize the host response to biomaterials. Similarly, control of DC phenotype from proinflammatory to toleragenic is of interest in vaccine delivery and tissue engineering/transplantation situations, respectively. This review discusses the interconnection between innate and adaptive immunity, the comparative and contrasting phenotypes and roles of Mφs and DCs in immunity, their responses to biomaterials and the strategies to modulate their phenotype for applications in tissue engineering and vaccine delivery. Furthermore, the collaboration between and unique roles of DCs and Mφs needs to be addressed in future studies to gain a more complete picture of host responses toward combination products. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. PMID: 21069873 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Enhanced osteogenic differentiation of cord blood-derived unrestricted somatic stem cells on electrospun nanofibers. J Mater Sci Mater Med. 2010 Nov 11; Authors: Seyedjafari E, Soleimani M, Ghaemi N, Sarbolouki MN A new stem cell-scaffold construct based on poly-L: -lactide (PLLA) nanofibers grafted with collagen (PLLA-COL) and cord blood-derived unrestricted somatic stem cells (USSC) were proposed to hold promising characteristics for bone tissue engineering. Fabricated nanofibers were characterized using SEM, ATR-FTIR, tensile and contact angle measurements. The capacity of PLLA, plasma-treated PLLA (PLLA-pl) and PLLA-COL scaffolds to support proliferation and osteogenic differentiation of USSC was evaluated using MTT assay and common osteogenic markers such as alkaline phosphatase (ALP) activity, calcium mineral deposition and bone-related genes. All three scaffolds showed nanofibrous and porous structure with suitable physical characteristics. Higher proliferation and viability of USSC was observed on PLLA-COL nanofibers compared to control surfaces. In osteogenic medium, ALP activity and calcium deposition exhibited the highest values on PLLA-COL scaffolds on days 7 and 14. These markers were also greater on PLLA and PLLA-pl compared to TCPS. Higher levels of collagen I, osteonectin and bone morphogenetic protein-2 were detected on PLLA-COL compared to PLLA and PLLA-pl. Runx2 and osteocalcin were also expressed continuously on all scaffolds during induction. These observations suggested the enhanced proliferation and osteogenic differentiation of USSC on PLLA-COL nanofiber scaffolds and introduced a new combination of stem cell-scaffold constructs with desired characteristics for application in bone tissue engineering. PMID: 21069560 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Scaffolds with a standardized macro-architecture fabricated from several calcium phosphate ceramics using an indirect rapid prototyping technique. J Mater Sci Mater Med. 2010 Nov 11; Authors: Wilson CE, van Blitterswijk CA, Verbout AJ, Dhert WJ, de Bruijn JD Calcium phosphate ceramics, commonly applied as bone graft substitutes, are a natural choice of scaffolding material for bone tissue engineering. Evidence shows that the chemical composition, macroporosity and microporosity of these ceramics influences their behavior as bone graft substitutes and bone tissue engineering scaffolds but little has been done to optimize these parameters. One method of optimization is to place focus on a particular parameter by normalizing the influence, as much as possible, of confounding parameters. This is difficult to accomplish with traditional fabrication techniques. In this study we describe a design based rapid prototyping method of manufacturing scaffolds with virtually identical macroporous architectures from different calcium phosphate ceramic compositions. Beta-tricalcium phosphate, hydroxyapatite (at two sintering temperatures) and biphasic calcium phosphate scaffolds were manufactured. The macro- and micro-architectures of the scaffolds were characterized as well as the influence of the manufacturing method on the chemistries of the calcium phosphate compositions. The structural characteristics of the resulting scaffolds were remarkably similar. The manufacturing process had little influence on the composition of the materials except for the consistent but small addition of, or increase in, a beta-tricalcium phosphate phase. Among other applications, scaffolds produced by the method described provide a means of examining the influence of different calcium phosphate compositions while confidently excluding the influence of the macroporous structure of the scaffolds. PMID: 21069558 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Skingineering II: transplantation of large-scale laboratory-grown skin analogues in a new pig model. Pediatr Surg Int. 2010 Nov 11; Authors: Schiestl C, Biedermann T, Braziulis E, Hartmann-Fritsch F, Böttcher-Haberzeth S, Arras M, Cesarovic N, Nicolls F, Linti C, Reichmann E, Meuli M BACKGROUND: Tissue engineering of skin with near-normal anatomy is an intriguing novel strategy to attack the still unsolved problem of how to ideally cover massive full-thickness skin defects. After successful production of large, pig cell-derived skin analogues, we now aim at developing an appropriate large animal model for transplantation studies. MATERIALS AND METHODS: In four adult Swiss pigs, full-thickness skin defects, measuring 7.5 × 7.5 cm, were surgically created and then shielded against the surrounding skin by a new, self-designed silicone chamber. In two animals each, Integra dermal regeneration templates or cultured autologous skin analogues, respectively, were applied onto the wound bed. A sophisticated shock-absorbing dressing was applied for the ensuing 3 weeks. Results were documented photographically and histologically. RESULTS: All animals survived uneventfully. Integra healed in perfectly, while the dermo-epidermal skin analogues showed complete take of the dermal compartment but spots of missing epidermis. The chamber proved effective in precluding ("false positive") healing from the wound edges and the special dressing efficiently kept the operation site intact and clean for the planned 3 weeks. CONCLUSION: We present a novel and valid pig model permitting both transplantation of large autologous, laboratory-engineered skin analogues and also keeping the site of intervention undisturbed for at least three postoperative weeks. Hence, the model will be used for experiments testing whether such large skin analogues can restore near-normal skin, particularly in the long term. If so, clinical application can be envisioned. PMID: 21069348 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Measurement of adherent cell mass and growth. Proc Natl Acad Sci U S A. 2010 Nov 10; Authors: Park K, Millet LJ, Kim N, Li H, Jin X, Popescu G, Aluru NR, Hsia KJ, Bashir R The characterization of physical properties of cells such as their mass and stiffness has been of great interest and can have profound implications in cell biology, tissue engineering, cancer, and disease research. For example, the direct dependence of cell growth rate on cell mass for individual adherent human cells can elucidate the mechanisms underlying cell cycle progression. Here we develop an array of micro-electro-mechanical systems (MEMS) resonant mass sensors that can be used to directly measure the biophysical properties, mass, and growth rate of single adherent cells. Unlike conventional cantilever mass sensors, our sensors retain a uniform mass sensitivity over the cell attachment surface. By measuring the frequency shift of the mass sensors with growing (soft) cells and fixed (stiff) cells, and through analytical modeling, we derive the Young's modulus of the unfixed cell and unravel the dependence of the cell mass measurement on cell stiffness. Finally, we grew individual cells on the mass sensors and measured their mass for 50+ hours. Our results demonstrate that adherent human colon epithelial cells have increased growth rates with a larger cell mass, and the average growth rate increases linearly with the cell mass, at 3.25%/hr. Our sensitive mass sensors with a position-independent mass sensitivity can be coupled with microscopy for simultaneous monitoring of cell growth and status, and provide an ideal method to study cell growth, cell cycle progression, differentiation, and apoptosis. PMID: 21068372 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Inorganic/Organic Biocomposite Cryogels for Regeneration of Bony Tissues. J Biomater Sci Polym Ed. 2010 Nov 9; Authors: Mishra R, Kumar A The present work focuses on the physical, mechanical and in vitro properties of porous inorganic/organic biocomposite scaffolds of polyvinyl alcohol-tetraethylorthosilicate-alginate-calcium oxide (PTAC). These scaffolds are prepared by means of cryogelation technology and are intended for bone tissue engineering applications. The biocomposite cryogels have much more favorable physical and biological properties compared to the previous work of our group on the same composition in the form of pellets and foams. The optimized and heat-treated PTAC biocomposite cryogels show homogenous porosity and good mechanical properties and also exhibit the formation of a hydroxyapatite-like layer on their surface on coming in contact with simulated body fluid (SBF). Furthermore, the biocomposite cryogels showed good biocompatibility with L929 fibroblasts. Also, the influence of pre-soaking in SBF to that of non-soaked scaffolds was compared in terms of proliferation of MG-63 osteoblast-like osteosarcoma cells on these scaffolds and it was found that the pre-soaking caused a decrease in cell proliferation. Finally, the response of human osteoblasts on these scaffolds was analyzed by MTT assay, scanning electron microscopy, energy dispersive X-ray spectroscopy and micro X-ray computing tomography. The cells revealed good biocompatibility with the biocomposite cryogels and were mostly present as cell sheets on the surface with thick bundles of collagenous extracellular matrix during initial period of incubation. During later phases, the formation of calcium phosphate-like mineral deposits was observed on the surface of the cryogels suggesting a high potential of the biocomposite cryogels towards bone regeneration. Therefore, the PTAC biocomposite cryogels, due to their favorable properties and high biocompatibility with human osteoblasts can be suggested as potential scaffolds for bone tissue engineering applications. PMID: 21067655 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | An update on new oral PDE5 inhibitors for the treatment of erectile dysfunction. Nat Rev Urol. 2010 Nov;7(11):603-9 Authors: Palit V, Eardley I The management of erectile dysfunction (ED) has been revolutionized by the discovery of phosphodiesterase 5 (PDE5) inhibitors, which have been commercially available for more than a decade and are the first-line therapeutic option for men with ED. Sildenafil, vardenafil and tadalafil were approved by the European Medicine Agency and the US FDA for the treatment of ED on the back of their high efficacy rates and favorable safety profiles. However, despite the fact that more than 50 million patients with ED worldwide have been successfully treated with one of these PDE5 inhibitors, some men-most notably those with severe neurologic damage, diabetes mellitus or severe vascular disease-are resistant to the currently available drugs and require more-invasive treatments, such as intracavernosal injection therapy. Partly as a consequence of this, research into alternative therapeutic approaches continues, including the development of new PDE5 inhibitors, centrally acting pharmaceutical agents, and application of molecular technologies such as gene therapy and stem cell therapy. PMID: 21068761 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal-Lineage Stem Cells Have Pronounced Anti-Inflammatory Effects in the Twitcher Mouse Model of Krabbe's Disease. Stem Cells. 2010 Nov 9; Authors: Ripoll CB, Flaat M, Klopf-Eiermann J, Fisher-Perkins JM, Trygg CB, Scruggs BA, McCants ML, Leonard HP, Lin AF, Zhang S, Eagle ME, Alvarez X, Li YT, Li SC, Gimble JM, Bunnell BA The twitcher mouse is an animal model of Krabbe's disease which is a neurodegenerative lysosomal storage disorder resulting from the absence of functional lysosomal enzyme galactocerebrosidase (GALC). This disease affects the central and peripheral nervous systems and in its most severe form results in death before the age of 2 years old in humans and approximately 30-40 days in mice. This study evaluates the effect of intracerebroventricular administration of mesenchymal stem cells derived from adipose tissue (ASCs) and bone marrow (BMSCs) on the pathology of Krabbe's disease.Subsequent to the intracerebroventricular injection of ASCs or BMSCs on post-natal day (PND) 3-4, body weights, lifespan, and neuromotor function were evaluated longitudinally beginning on PND15. At sacrifice, tissues were harvested for analysis of GALC activity, presence of myelin, infiltration of macrophages, microglial activation, inflammatory markers, and cellular persistence.Survival analysis curves indicate a statistically significant increase in lifespan in stem cell treated as compared to control twitcher mice. Body weights and motor function were also improved compared to controls. The stem cells may mediate some of these benefits through an anti-inflammatory mechanism because the expression of numerous pro-inflammatory markers was down-regulated at both transcriptional and translational levels. A marked decrease in the levels of macrophage infiltration and microglial activation were also noted.These data indicate that mesenchymal lineage stem cells are potent inhibitors of inflammation associated with Krabbe's disease progression and offer potential benefits as a component of a combination approach for in vivo treatment by reducing the levels of inflammation. PMID: 21064113 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic efficacy and safety of TRAIL-producing human adipose tissue-derivedmesenchymal stem cells againstexperimental brainstem glioma. Neuro Oncol. 2010 Nov 9; Authors: Choi SA, Hwang SK, Wang KC, Cho BK, Phi JH, Lee JY, Jung HW, Lee DH, Kim SK Mesenchymal stem cells (MSCs) have an extensive migratory capacity for gliomas, which is comparable to that of neural stem cells. Among the various types of MSCs, human adipose tissue-derived MSCs (hAT-MSC) emerge as one of the most attractive vehicles for gene therapy because of their high throughput, lack of ethical concerns, and availability and ease of isolation. We evaluated the therapeutic potential and safety of genetically engineered hAT-MSCs encoding the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against brainstem gliomas. Human AT-MSCs were isolated from human fat tissue, characterized, and transfected with TRAIL using nucleofector. The therapeutic potential of TRAIL-producing hAT-MSCs (hAT-MSC.TRAIL) was confirmed using in vitro and in vivo studies. The final fate of injected hAT-MSCs was traced in long-survival animals. The characterization of hAT-MSCs revealed the expression of MSC-specific cell-type markers and their differentiation potential into mesenchymal lineage. Short-term outcomes included a 56.3% reduction of tumor volume (P < .001) with increased apoptosis (3.03-fold, P < .05) in animals treated with hAT-MSC.TRAIL compared with the control groups. Long-term outcomes included a significant survival benefit in the hAT-MSC.TRAIL-treated group (26 days of median survival in the control group vs 84 days in the hAT-MSC.TRAIL-treated group, P < .0001), without any evidence of mesenchymal differentiation in vivo. Our study demonstrated the therapeutic efficacy and safety of nonvirally engineered hAT-MSCs against brainstem gliomas and showed the possibility of stem-cell-based targeted gene therapy for clinical application. PMID: 21062796 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Determination of adipose-derived stem cell application on photo-aged fibroblasts, based on paracrine function. Cytotherapy. 2010 Nov 9; Authors: Song SY, Jung JE, Jeon YR, Tark KC, Lew DH Abstract Background aims. Adipose-derived stem cells (ASC) are known to be able to restore injured tissue via differentiation and paracrine effects. In this study, we investigated the effect of ASC on photo-aged human dermal fibroblasts (HDF) based on paracrine function. In particular, we wanted to determine a more effective method of ASC application and the fate of the photo-aged fibroblasts. Methods. We compared two application methods of ASC: transwell and conditioned medium culture with photo-aged fibroblasts. Proliferation rate, collagen synthesis, matrix metalloproteinase (MMP) production and expression of p16 were measured by real-time polymerase chain reaction (PCR) after culture. Flow cytometry for apoptosis assay was also conducted to determine the fate of the photo-aged fibroblasts. Results. ASC induced proliferation of photo-aged HDF and type I collagen production and decreased MMP-1 production and expression of p16. In an apoptosis assay, ASC converted necrotic or late apoptotic cells to early apoptotic cells. These results were similar in both experimental groups. Conclusions. The results indicate that the paracrine effects of ASC may have a role that is as important as cell-to-cell communication between ASC and fibroblasts. We believe that conditioned medium may be a useful material for anti-aging skin therapy instead of cell therapy. Also, ASC might have an anti-aging effect on photo-aged fibroblasts even at a genetic level. PMID: 21062113 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch Clin Exp Ophthalmol. 2010 Oct;248(10):1415-22 Authors: Yang Z, Li K, Yan X, Dong F, Zhao C BACKGROUND: Diabetic retinopathy is a common complication of diabetes, which is caused by injury to retinal microvasculature and neurons. Mesenchymal stem cells (MSCs), which proved to have multi-linkage differentiation capacity, including endothelial cells and neurons, might be a promising cell therapy resource. The current pilot study was performed using the streptozotocin (STZ) rat model of diabetic retinopathy injected intravenously with human adipose-derived mesenchymal stem cells (AMSCs) in an effort to investigate the potency and possible therapeutic effects of AMSCs. METHODS: Four experimental groups of Wistar rats were included in the current study: an untreated control group of STZ diabetic rats (n = 10), a normal non-diabetic control group (n = 20), an AMSC therapy group of STZ diabetic rats (n = 50), and a sham group of STZ diabetic rats (n = 50). Blood glucose levels were monitored closely. Immunofluorescence was used to study AMSC distribution and differentiation. The integrity of the blood-retinal barrier (BRB) was evaluated by Evans blue dye infusion to evaluate the therapeutic effects. RESULTS: After 1 week of transplantation, a significant reduction in blood glucose levels was observed in the AMSC therapy group relative to the sham group. BRB integrity was also improved, as less Evans blue dye leakage was observed. Donor cells were observed in the retinas of therapy group rats, and they expressed rhodopsin and glial fibrillary acidic protein (GFAP), specific markers for photoreceptors and astrocytes, respectively. CONCLUSIONS: Taken together, the results of the current study suggest that AMSCs may improve the integrity of the BRB in diabetic rats by differentiation into photoreceptor and glial-like cells in the retina and by reducing the blood glucose levels. Furthermore, the data presented herein provide evidence that AMSCs may serve as a promising therapeutic approach for diabetic retinopathy. PMID: 20437245 [PubMed - indexed for MEDLINE] | | | | | | | | | |  | |  | |  |
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