|  |  |  | | | | | TERMSC | | | | | | | | | | | | | | | | | | | Improved seeding of chondrocytes into polyglycolic acid scaffolds using semi-static and alginate loading methods. Biotechnol Prog. 2010 Sep 14; Authors: Shahin K, Doran PM Cell seeding and attachment in three-dimensional scaffolds is a key step in tissue engineering with implications for cell differentiation and tissue development. In this work, two new seeding methods were investigated using human chondrocytes and polyglycolic acid (PGA) fibrous mesh scaffolds. A simple semi-static seeding method using culture plates and tissue flasks was developed as an easy-to-perform modification of static seeding. An alginate-loading method was also studied, using alginate hydrogel as an adjuvant for entrapping cells within PGA scaffolds. Both the semi-static and PGA-alginate methods produced more homogeneous cell distributions than conventional static and dynamic seeding. Using 20 × 10(6) cells, whereas the seeding efficiency for static seeding was only 52%, all other techniques produced seeding efficiencies of ≥ 90%. With 40 × 10(6) cells, the efficiency of semi-static seeding declined to 74% while the dynamic and PGA-alginate methods retained their ability to accommodate high cell numbers. The seeded scaffolds were cultured in recirculation bioreactors to determine the effect of seeding method on cartilage production. Statically seeded scaffolds did not survive the 5-week cultivation period. Deposition of extracellular matrix in scaffolds seeded using the semi-static and PGA-alginate methods was more uniform compared with scaffolds seeded using the dynamic method. The new semi-static and PGA-alginate seeding methods developed in this work are recommended for tissue engineering because they provide substantial benefits compared with static seeding in terms of seeding efficiency, cell distribution, and cartilage deposition while remaining simple and easy to execute. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010. PMID: 21064180 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Genipin-crosslinked microcarriers mediating hepatocellular aggregates formation and functionalities. J Biomed Mater Res A. 2010 Nov 9; Authors: Lau TT, Wang C, Png SW, Su K, Wang DA In engineered regenerative medicine, various types of scaffolds have been customized to pursue the optimal environment for different types of therapeutic cells. In liver therapeutic research, hepatocytes require attachment to solid anchors for survival and proliferation before they could grow into cellular aggregates with enhanced functionalities. Among the various biomaterials scaffolds and vehicles, microspherical cell carriers are suited to these requirements. Individual spheres may provide two-dimensional (2D) cell-affinitive surfaces for cell adhesion and spreading; whereas multiple microcarriers may form three-dimensional (3D) matrices with inter-spherical space for cell expansion and multicellular aggregation. In this study, we culture human liver carcinoma cell line (HepG2) cells on genipin-crosslinked gelatin microspheres of two different sizes. Results suggest that both microcarriers support cell adhesion, proliferation, and spontaneous formation of hepatocellular aggregates, among which the spheres with bigger size (200-300 μm) seem more favorable than the smaller ones in terms of aggregate formation and liver specific functionalities. These findings suggest that the genipin-crosslinked microcarrier is a competent vehicle for liver cell delivery. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 21064126 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Co-electrospun fibrous scaffold-adsorbed DNA for substrate-mediated gene delivery. J Biomed Mater Res A. 2010 Nov 9; Authors: Zhang J, Duan Y, Wei D, Wang L, Wang H, Gu Z, Kong D Incorporation of gene into electrospun nanofibers for localized gene transfection of target cells represents a robust platform for tissue regeneration. In this study, a new two-step approach was explored to immobilize DNA onto electrospun nanofibers for effective gene delivery, that is, nonviral gene vector of polyethylene glycol (PEG)-modified polyethylenimine (PEI) was incorporated into scaffolds by electrospinning and then target DNA was adsorbed onto the electrospun nanofibers via electrostatic interaction between DNA and PEI-PEG. PEI-PEG/DNA particles formed from the released DNA, and PEI-PEG had a uniform particle size of approximately 200 nm. This nanofiber-based gene delivery system exhibited high transfection efficiency, in which >65% of human embryonic kidney 293 cells and >40% of mesenchymal stem cells were transfected with green fluorescent protein gene. Compared with PEI, PEG modification of PEI had improved the biocompatibility and further increased the transfection efficiency. These results suggest that the combination of nonviral gene carrier with electrospun nanofibers could be used for localized gene delivery, which has multifold potential applications in tissue engineering or as an in vivo substrate for tissue regeneration. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010. PMID: 21064119 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Tribocorrosion behaviour of nanostructured titanium substrates processed by high-pressure torsion. Nanotechnology. 2010 Dec 3;21(48):485703 Authors: Faghihi S, Li D, Szpunar JA Aseptic loosening induced by wear particles from artificial bearing materials is one of the main causes of malfunctioning in total hip replacements. With the increase in young and active patients, complications in revision surgeries and immense health care costs, there is considerable interest in wear-resistant materials that can endure longer in the harsh and corrosive body environment. Here, the tribological behaviour of nanostructured titanium substrates processed by high-pressure torsion (HPT) is investigated and compared with the coarse-grained samples. The high resolution transmission electron microscopy reveals that a nanostructured sample has a grain size of 5-10 nm compared to that of ∼ 10 µm and ∼ 50 µm for untreated and annealed substrates, respectively. Dry and wet wear tests were performed using a linear reciprocating ball-on-flat tribometer. Nanostructured samples show the best dry wear resistance and the lowest wear rate in the electrolyte. There was significantly lower plastic deformation and no change in preferred orientation of nanostructured samples attributable to the wear process. Electrochemical impedance spectroscopy (EIS) shows lower corrosion resistance for nanostructured samples. However, under the action of both wear and corrosion the nanostructured samples show superior performance and that makes them an attractive candidate for applications in which wear and corrosion act simultaneously. PMID: 21063052 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | 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] | | | | | | | | | | | | | | | | | | | | | | | | | Regenerative medicine as applied to solid organ transplantation: current status and future challenges. Transpl Int. 2010 Nov 10; Authors: Orlando G, Baptista P, Birchall M, De Coppi P, Farney A, Guimaraes-Souza NK, Opara E, Rogers J, Seliktar D, Shapira-Schweitzer K, Stratta RJ, Atala A, Wood KJ, Soker S In the last two decades, regenerative medicine has shown the potential for "bench-to-bedside" translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting-edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using "natural tissue" scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom-made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immunosuppression. This review describes recent advances in the engineering of several key tissues and organs. PMID: 21062367 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Molecular physiology of cardiac regeneration. Ann N Y Acad Sci. 2010 Nov;1211(1):113-26 Authors: Bolli P, Chaudhry HW Heart disease is the leading cause of death in the industrialized world. This is partially attributed to the inability of cardiomyocytes to divide in a significant manner, and therefore the heart responds to injury through scar formation. One of the challenges of modern medicine is to develop novel therapeutic strategies to facilitate regeneration of cardiac muscle in the diseased heart. Numerous methods have been studied and a wide variety of cell types have been considered. To date, bone marrow stem cells, endogenous populations of cardiac stem cells, embryonic stem cells, and induced pluripotent stem cells have been investigated for their ability to regenerate infarcted myocardium, although stem cell transplantation has produced ambiguous results in human clinical trials. Several studies support another approach that seems very appealing: enhancing the limited endogenous regenerative capacity of the heart. The recent advances in stem cell and regenerative biology are giving rise to the view that cardiac regeneration, although not quite ready for clinical treatment, may translate into therapeutic reality in the not too distant future. PMID: 21062300 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Nanoparticles: Functionalization and Multifunctional Applications in Biomedical Sciences. Curr Med Chem. 2010 Nov 10; Authors: Subbiah R, Veerapandian M, Yun KS Rapid innovations in nanomedicine have increased the likelihood that engineered nanomaterials will eventually come in contact with humans and the environment. The advent of nanotechnology has created strong interest in many fields such as biomedical sciences and engineering field. Central to any significant advances in nanomaterial based applications will be the development of functionalized nanoparticles, which are believed to hold promise for use in fields such as pharmaceutical and biomedical sciences. Early clinical results have suggested that functionalization of nanoparticles with specific recognition chemical moieties indeed yields multifunctional nanoparticles with enhanced efficacy, while simultaneously reducing side effects, due to properties such as targeted localization in tumors and active cellular uptake. A prerequisite for advancing this area of research is the development of chemical methods to conjugate chemical moieties onto nanoparticles in a reliable manner. In recent years a variety of chemical methods have been developed to synthesize functionalized nanoparticles specifically for drug delivery, cancer therapy, diagnostics, tissue engineering and molecular biology, and the structure-function relationship of these functionalized nanoparticles has been extensively examined. With the growing understanding of methods to functionalize nanoparticles and the continued efforts of creative scientists to advance this technology, it is likely that functionalized nanoparticles will become an important tool in the above mentioned areas. Therefore, the aim of this review is to provide basic information on nanoparticles, describe previously developed methods to functionalize nanoparticles and discuss their potential applications in biomedical sciences. The information provided in this review is important in regards to the safe and widespread use of functionalized nanoparticles particularly in the biomedicine field. PMID: 21062250 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Functional neovascularization in tissue engineering with porcine acellular dermal matrix and human umbilical vein endothelial cells. Tissue Eng Part C Methods. 2010 Nov 10; Authors: Zhang X, Yang J, Li Y, Liu S, Long K, Zhao Q, Zhang Y, Deng Z, Jin Y Endothelial cells-matrix interactions play an important role in promoting and controlling network formation. In this study, porcine acellular dermal matrix (PADM) was used to guide human umbilical vein endothelial cells (HUVECs) adhesion and proliferation as a potential system for vascularization of engineered tissues. We fabricated PADM using a modified protocol and assessed their composition and ultrastructures. Subsequently, the viability of HUVECs and the formation of capillary-like networks were evaluated by seeding cells directly on PADM scaffolds or PADM digests in vitro. We further investigated the function of the HUVECs seeded on the PADM scaffolds after subcutaneous transplantation in athymic mice. Moreover, the function of the neovessels formed in the PADM scaffolds were assessed by implantation into cutaneous wounds on the backs of mice. The results showed that PADM scaffolds significantly increased proliferation of HUVECs, and the PADM digest induced HUVECs formed many tube-like structures. Moreover, HUVECs seeded on the PADM scaffolds formed numerous capillary-like networks and some perfused vascular structures following implantation into mice. PADM seeded with HUVECs and fibroblasts were also able to form many capillary-like networks in vitro. Furthermore, these neovessels could inosculate with the murine vasculature after implantation into cutaneous wounds in mice. The advantage of this method is that the decellularized matrix not only provides signals to maintain the viability of endothelial cells but also serves as the template structure for regenerated tissue. These findings indicate that PADM seeded with HUVECs may be a potential system for successful engineering of large, thick and complex tissues. PMID: 21062229 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Epithelial-Mesenchymal Interactions As a Working Concept for Oral Mucosa Regeneration. Tissue Eng Part B Rev. 2010 Nov 10; Authors: Liu J, Mao J, Chen L Oral mucosa consists of two tissue layers, the superficial epithelium and the underlying lamina propria. Together, oral mucosa functions as a barrier against exogenous substances and pathogens. In development, interactions of stem/progenitor cells of the epithelium and mesenchyme are crucial to the morphogenesis of oral mucosa. Previous work in oral mucosa regeneration has yielded important clues for several meritorious proof of concept approaches. Tissue engineering offers a broad array of novel tools for oral mucosa regeneration with reduced donor site trauma and accelerated clinical translation. However, the developmental concept of epithelial-mesenchymal interactions is rarely considered in oral mucosa regeneration. Epithelial-mesenchymal interactions in postnatal oral mucosa regeneration likely will not be a simple recapitulation of prenatal oral mucosa development. Biomaterial scaffolds play an indispensible role for oral mucosa regeneration and should provide a conducive environment for pivotal epithelial-mesenchymal interactions. Autocrine and paracrine factors, either exogenously delivered or innately produced, have rarely been and should be harnessed to promote oral mucosa regeneration. This review focuses on a working concept of epithelial and mesenchymal interactions in oral mucosa regeneration. PMID: 21062224 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Carbon nanotubes in animal models: a systematic review on toxic potential. Tissue Eng Part B Rev. 2010 Nov 10; Authors: van der Zande M, Junker R, Walboomers XF, Jansen J Amongst the engineered nanomaterials, especially carbon nanotubes (CNTs) have received considerable attention for application in tissue engineering scaffolds. CNTs are considered promising on behalf of their physicochemical properties, yet such nanomaterials also have been associated with potentially hazardous effects on human health. To gain insight in the toxicity aspects of CNTs <i>in vivo</i>, the current study presents a systematic review of literature. After screening of literature through defined inclusion and exclusion criteria, and subsequent data extraction, it can be concluded that pulmonary administered CNTs have the capacity to induce toxicity in the lung area. However, conclusions for other organs, or on systemic toxicity, are yet premature. In addition, the carcinogenic potential of CNTs is also still ambiguous, since contradictive results are presented. Intrinsic factors, like material characteristics and associated distribution- and agglomeration patterns are of influence on the toxic potential of CNTs. Similarly, environmental factors like the exposure route, pre-existing allergies, pathological infections, or air pollutant exposure are significant. In spite of the many reports published currently, more studies will be required to gain full understanding of the toxic potential of CNTs and especially the underlying mechanisms. For this end, development of standardized protocols and reliable nanodetection techniques will form prerequisites. PMID: 21062222 [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] | | | | | | | | | | | | | | | | | | | | | | | | | Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery. J Cardiovasc Transl Res. 2010 Nov 9; Authors: Gowdak LH, Schettert IT, Rochitte CE, Lisboa LA, Dallan LA, César LA, de Oliveira SA, Krieger JE Incomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 ± 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 ± 1.3 × 10(8) BMC (CD34+ = 0.8 ± 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with <50% (group A, n = 11) with that of patients with >50% (group B, n = 10) of target vessels (stenosis ≥ 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 ± 0.8) was significantly smaller than the number of target vessels (4.2 ± 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 ± 3.2), compared to patients in group B (78.1 ± 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization. PMID: 21061106 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Human placenta-derived mesenchymal stem cells and islet-like cell clusters generated from these cells as a novel source for stem cell therapy in diabetes. Rev Diabet Stud. 2010;7(2):168-82 Authors: Kadam S, Muthyala S, Nair P, Bhonde R Placental tissue holds great promise as a source of cells for regenerative medicine due to its plasticity, and easy availability. Human placenta-derived mesenchymal stem cells (hPDMSCs) have the potential to differentiate into insulin-producing cells. Upon transplantation, they can reverse experimental diabetes in mice. However, it is not known whether culture-expanded undifferentiated hPDMSCs are capable of restoring normoglycemia upon transplantation in streptozotocin (STZ)-induced diabetic mice. Hence we prepared long-term cultures of hPDMSCs from the chorionic villi of full-term human placenta. Flow cytometry analyses and immunocytochemistry study revealed bonafide mesenchymal nature of the isolated hPDMSCs. These cultures could differentiate into adipogenic, oesteogenic, chondrogenic, and neuronal lineages on exposure to lineage-specific cocktails. Furthermore, we showed that hPDMSCs can form islet-like cell clusters (ILCs) on stepwise exposure to serum-free defined media containing specific growth factors and differentiating agents. qRT-PCR showed the expression of insulin, glucagon, and somatostatin in undifferentiated hPDMSCs and in ILCs. Differentiated ILCs were found to express human insulin, glucagon, and somatostatin by immunocytochemistry. Additionally, ILCs also showed abundance of pancreatic transcription factors ngn3 and isl1. Both undifferentiated hPDMSCs and ILCs exihibited insulin secretion in response to glucose. Transplantation of hPDMSCs or ILCs derived from hPDMSCs in STZ-induced diabetic mice led to restoration of normoglycemia. Our results demonstrate, for the first time, reversal of hyperglycemia by undifferentiated hPDMSCs and ILCs derived from hPDMSCs. These results suggest human placenta-derived MSCs as an alternative source for cell replacement therapy in diabetes. PMID: 21060975 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Prospects of Stem Cell Therapy in Diabetes - Introduction to the RDS Special Issue. Rev Diabet Stud. 2010;7(2):80-1 Authors: Efrat S PMID: 21060966 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Signaling by FGFR2b controls the regenerative capacity of adult mouse incisors. Development. 2010 Nov;137(22):3743-52 Authors: Parsa S, Kuremoto K, Seidel K, Tabatabai R, Mackenzie B, Yamaza T, Akiyama K, Branch J, Koh CJ, Al Alam D, Klein OD, Bellusci S Rodent incisors regenerate throughout the lifetime of the animal owing to the presence of epithelial and mesenchymal stem cells in the proximal region of the tooth. Enamel, the hardest component of the tooth, is continuously deposited by stem cell-derived ameloblasts exclusively on the labial, or outer, surface of the tooth. The epithelial stem cells that are the ameloblast progenitors reside in structures called cervical loops at the base of the incisors. Previous studies have suggested that FGF10, acting mainly through fibroblast growth factor receptor 2b (FGFR2b), is crucial for development of the epithelial stem cell population in mouse incisors. To explore the role of FGFR2b signaling during development and adult life, we used an rtTA transactivator/tetracycline promoter approach that allows inducible and reversible attenuation of FGFR2b signaling. Downregulation of FGFR2b signaling during embryonic stages led to abnormal development of the labial cervical loop and of the inner enamel epithelial layer. In addition, postnatal attenuation of signaling resulted in impaired incisor growth, characterized by failure of enamel formation and degradation of the incisors. At a cellular level, these changes were accompanied by decreased proliferation of the transit-amplifying cells that are progenitors of the ameloblasts. Upon release of the signaling blockade, the incisors resumed growth and reformed an enamel layer, demonstrating that survival of the stem cells was not compromised by transient postnatal attenuation of FGFR2b signaling. Taken together, our results demonstrate that FGFR2b signaling regulates both the establishment of the incisor stem cell niches in the embryo and the regenerative capacity of incisors in the adult. PMID: 20978072 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Definition and validation of operating equations for poly(vinyl alcohol)-poly(lactide-co-glycolide) microfiltration membrane-scaffold bioreactors. Biotechnol Bioeng. 2010 Oct 1;107(2):382-92 Authors: Shipley RJ, Waters SL, Ellis MJ The aim of this work is to provide operating data for biodegradable hollow fiber membrane bioreactors. The physicochemical cell culture environment can be controlled with the permeate flowrate, so this aim necessitates the provision of operating equations that enable end-users to set the pressures and feed flowrates to obtain their desired culture environment. In this paper, theoretical expressions for the pure water retentate and permeate flowrates, derived using lubrication theory, are compared against experimental data for a single fiber poly(vinyl alcohol)-poly(lactide-co-glycolide) crossflow module to give values for the membrane permeability and slip. Analysis of the width of the boundary layer region where slip effects are important, together with the sensitivity of the retentate and permeate equations to the slip parameter, show that slip is insignificant for these membranes, which have a mean pore diameter of 1.1 microm. The experimental data is used to determine a membrane permeability, of k = 1.86 x 10(-16) m(2), and to validate the model. It was concluded that the operating equation that relates the permeate to feed ratio, c, lumen inlet flowrate, Q (l,in), lumen outlet pressure, P (1), and ECS outlet pressure, P (0), is P(1) - P(0) = Q(l),in (Ac + B) where A and B are constants that depend on the membrane permeability and geometry (and are given explicitly). Finally, two worked examples are presented to demonstrate how a tissue engineer can use Equation (1) to specify operating conditions for their bioreactor. PMID: 20641054 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Multi-lineage differentiation of hMSCs encapsulated in thermo-reversible hydrogel using a co-culture system with differentiated cells. Biomaterials. 2010 Oct;31(28):7275-87 Authors: Park JS, Yang HN, Woo DG, Kim H, Na K, Park KH The micro-environment is an important factor in the differentiation of cultured stem cells for the purpose of site specific transplantation. In an attempt to optimize differentiation conditions, co-culture systems composed of both stem cells and primary cells or cell lines were used in hydrogel with in vitro and in vivo systems. Stem cells encapsulated in hydrogel, under certain conditions, can undergo increased differentiation both in vitro and in vivo; therefore, reconstruction of transplanted stem cells in a hydrogel co-culture system is important for tissue regeneration. In order to construct such a co-culture system, we attempted to create a hydrogel scaffold which could induce neo-tissue growth from the recipient bed into the material. This material would enable encapsulation of stem cells in vitro after which they could be transferred to an in vivo system utilizing nude mice. In this case, the hydrogel was implanted in the subfascial space of nude mice and excised 4 weeks later. Cross-sections of the excised samples were stained with von Kossa or safranin-O and tubular formations into the gel were observed with and tested by doppler imaging. The data showed that the hydrogel markedly induced growth of osteogenic, chondrogenic, and vascular-rich tissue into the hydrogel by 4 weeks, which surpassed that after transplantation in a co-culture system. Further, a co-culture system with differentiated cells and stem cells potentially enhanced chondrogenesis, osteogenesis, and vascularization. These findings suggest that a co-culture system with hydrogel as scaffold material for neo-tissue formation is a useful tools for multi-lineage stem cell differentiation. PMID: 20619450 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Laser assisted bioprinting of engineered tissue with high cell density and microscale organization. Biomaterials. 2010 Oct;31(28):7250-6 Authors: Guillotin B, Souquet A, Catros S, Duocastella M, Pippenger B, Bellance S, Bareille R, Rémy M, Bordenave L, Amédée J, Guillemot F Over this decade, cell printing strategy has emerged as one of the promising approaches to organize cells in two and three dimensional engineered tissues. High resolution and high speed organization of cells are some of the key requirements for the successful fabrication of cell-containing two or three dimensional constructs. So far, none of the available cell printing technologies has shown an ability to concomitantly print cells at a cell-level resolution and at a kHz range speed. We have studied the effect of the viscosity of the bioink, laser energy, and laser printing speed on the resolution of cell printing. Accordingly, we demonstrate that a laser assisted cell printer can deposit cells with a microscale resolution, at a speed of 5 kHz and with computer assisted geometric control. We have successfully implemented such a cell printing precision to print miniaturized tissue like layouts with de novo high cell density and micro scale organization. PMID: 20580082 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Extent of cell differentiation and capacity for cartilage synthesis in human adult adipose-derived stem cells: comparison with fetal chondrocytes. Biotechnol Bioeng. 2010 Oct 1;107(2):393-401 Authors: Mahmoudifar N, Doran PM This study evaluated the extent of differentiation and cartilage biosynthetic capacity of human adult adipose-derived stem cells relative to human fetal chondrocytes. Both types of cell were seeded into nonwoven-mesh polyglycolic acid (PGA) scaffolds and cultured under dynamic conditions with and without addition of TGF-beta1 and insulin. Gene expression for aggrecan and collagen type II was upregulated in the stem cells in the presence of growth factors, and key components of articular cartilage such as glycosaminoglycan (GAG) and collagen type II were synthesized in cultured tissue constructs. However, on a per cell basis and in the presence of growth factors, accumulation of GAG and collagen type II were, respectively, 3.4- and 6.1-fold lower in the stem cell cultures than in the chondrocyte cultures. Although the stem cells synthesized significantly higher levels of total collagen than the chondrocytes, only about 2.4% of this collagen was collagen type II. Relative to cultures without added growth factors, treatment of the stem cells with TGF-beta1 and insulin resulted in a 59% increase in GAG synthesis, but there was no significant change in collagen production even though collagen type II gene expression was upregulated 530-fold. In contrast, in the chondrocyte cultures, synthesis of collagen type II and levels of collagen type II as a percentage of total collagen more than doubled after growth factors were applied. Although considerable progress has been achieved to develop differentiation strategies and scaffold-based culture techniques for adult mesenchymal stem cells, the extent of differentiation of human adipose-derived stem cells in this study and their capacity for cartilage synthesis fell considerably short of those of fetal chondrocytes. PMID: 20506225 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | 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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