|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | Robert Klein, the first and only chairman of the $3 billion California stem cell agency, has officially resigned effective June 23.
His resignation came in a May 10 letter to the statewide officials who are responsible for nominating candidates for chair of the unprecedented research effort, which is generally regarded as the single largest source of funding in the world for human embryonic | | | | | | | | | | | | | | | | | | | | | | | | | [Comparison of Chondrogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells with Cultured Chondrocytes and Bone Marrow Mesenchymal Stem Cells.] Acta Chir Orthop Traumatol Cech. 2011;78(2):138-144 Authors: Havlas V, Kos P, Jendelová P, Lesný P, Trč T, Syková E PURPOSE OF THE STUDY Many congenital and acquired disorders as well as sequelae of injury are associated with articular cartilage degenera- tion, which adversely affects the patient's quality of life. The currently used cell therapy with cultured chondrocytes has its disadvantages due to a process of de-differentiation of chondrocytes during cultivation. We believe that the mesenchymal stem cell therapy offers a new treatment options. MATERIAL AND METHODS The adult mesenchymal stem cells (MSCs) for chondrocyte differentiation are usually obtained from bone marrow mesen- chymal stem cells (BMSCs). In this study these cells were compared with mesenchymal stem cells derived from adipose tissue (AMSCs). The aim of the study was to verify the ability of human BMSCs and AMSCs to differentiate into chondro- cytes in vitro in the presence or absence of transforming growth factor beta (TGF-ß1). Human BMSCs and AMSCs were collected from healthy donors during orthopaedic surgeries, in vitro cultured in three passages to obtain the required quan- tity of cells. A pellet culture system was used for chondrocyte differentiation. RESULTS At 21 days of cultivation, cell aggregates grown in the chondrogenic medium were larger than those cultured in the con- trol medium. Both the BMSCs and AMSCs pellet cultures showed spontaneous chondrogenesis. Histological staining with haematoxylin and eosin and Masson's trichrome stains, as well as immunohistochemical staining to detect type II collagen revealed no apparent differences between the pellet cultures with TGF-ß1 presence and those without it. The real-time RT-PCR detected expression of the type II collagen gene in all tested cultures. In the BMSCs pellet culture only, TGF-ß1 presence resulted in a decrease in type I collagen mRNA levels and in an increase in type II collagen mRNA values. DISCUSSION Our results showed an in vitro chondrogenic potential of mature human mesenchymal stem cells derived from both bone marrow and adipose tissue. In agreement with the relevant literature data, we suggest that both cell types have an equal prospect for use in cartilage tissue engineering. Key words: bone marrow, adipose tissue, transforming growth factor beta, cartilage, pellet culture system. PMID: 21575557 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stroke rehabilitation. Lancet. 2011 May 14;377(9778):1693-702 Authors: Langhorne P, Bernhardt J, Kwakkel G Stroke is a common, serious, and disabling global health-care problem, and rehabilitation is a major part of patient care. There is evidence to support rehabilitation in well coordinated multidisciplinary stroke units or through provision of early supported provision of discharge teams. Potentially beneficial treatment options for motor recovery of the arm include constraint-induced movement therapy and robotics. Promising interventions that could be beneficial to improve aspects of gait include fitness training, high-intensity therapy, and repetitive-task training. Repetitive-task training might also improve transfer functions. Occupational therapy can improve activities of daily living; however, information about the clinical effect of various strategies of cognitive rehabilitation and strategies for aphasia and dysarthria is scarce. Several large trials of rehabilitation practice and of novel therapies (eg, stem-cell therapy, repetitive transcranial magnetic stimulation, virtual reality, robotic therapies, and drug augmentation) are underway to inform future practice. PMID: 21571152 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | The domestic cat as a large animal model for characterization of disease and therapeutic intervention in hereditary retinal blindness. J Ophthalmol. 2011;2011:906943 Authors: Narfström K, Holland Deckman K, Menotti-Raymond M Large mammals, including canids and felids, are affected by spontaneously occurring hereditary retinal diseases with similarities to those of humans. The large mammal models may be used for thorough clinical characterization of disease processes, understanding the effects of specific mutations, elucidation of disease mechanisms, and for development of therapeutic intervention. Two well-characterized feline models are addressed in this paper. The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene. The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene. Therapeutic trials have been performed mainly in the former type including stem cell therapy, retinal transplantation, and development of ocular prosthetics. Domestic cats, having large human-like eyes with comparable spontaneous retinal diseases, are also considered useful for gene replacement therapy, thus functioning as effective model systems for further research. PMID: 21584261 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Fabrication of chitin-chitosan/nano ZrO(2) composite scaffolds for tissue engineering applications. Int J Biol Macromol. 2011 May 7; Authors: Jayakumar R, Ramachandran R, Sudheesh Kumar PT, Divyarani VV, Srinivasan S, Chennazhi KP, Tamura H, Nair SV The urge to repair and regenerate natural tissues can now be satisfactorily fulfilled by various tissue engineering approaches. Chitin and chitosan are the most widely accepted biodegradable and biocompatible materials subsequent to cellulose. The incorporation of nano ZrO(2) onto the chitin-chitosan scaffold is thought to enhance osteogenesis. Hence a nanocomposite scaffold was fabricated by lyophilization technique using chitin-chitosan with nano ZrO(2). The prepared nanocomposite scaffolds were characterized using SEM, FTIR, XRD and TGA. In addition, the swelling, degradation, biomineralization, cell viability and cell attachment of the composite scaffolds were also evaluated. The results demonstrated better swelling and controlled degradation in comparison to the control scaffold. Cell viability studies proved the non toxic nature of the nanocomposite scaffolds. Cells were found to be attached to the pore walls and spread uniformly throughout the scaffolds. All these results suggested that the developed nanocomposite scaffolds possess the prerequisites for tissue engineering scaffolds and could be used for various tissue engineering applications. PMID: 21575656 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Adipose tissue as a stem cell source for musculoskeletal regeneration. Front Biosci (Schol Ed). 2011;3:69-81 Authors: Gimble JM, Grayson W, Guilak F, Lopez MJ, Vunjak-Novakovic G Adipose tissue is an abundant, easily accessible, and reproducible cell source for musculo-skeletal regenerative medicine applications. Initial derivation steps yield a heterogeneous population of cells of stromal vascular fraction (SVF) cells. Subsequent adherent selection of the SVF results in a relatively homogeneous population of adipose-derived stromal/stem cells (ASCs) capable of adipogenic, chondrogenic, myogenic, and osteogenic differentiation in vitro on scaffolds in bioreactors and in vivo in pre-clinical animal models. Unlike hematopoietic cells, ASCs do not elicit a robust lymphocyte reaction and instead release immunosuppressive factors, such as prostaglandin E2. These immunomodulatory features suggest that allogeneic and autologous ASCs will engraft successfully for tissue regeneration purposes. The differentiation and expansion potential of ASCs can be modified by growth factors, bio-inductive scaffolds, and bioreactors providing environmental control and biophysical stimulation. Gene therapy approaches using lentiviral transduction can be used to direct differentiation of ASCs to particular lineages. We discuss the utility of ASCs for musculo-skeletal tissue repair and some of the technologies that can be implemented to unlock the full regenerative potential of these highly valuable cells. PMID: 21196358 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Undifferentiated human adipose tissue-derived stromal cells induce mandibular bone healing in rats. Arch Otolaryngol Head Neck Surg. 2011 May;137(5):463-70 Authors: Parrilla C, Saulnier N, Bernardini C, Patti R, Tartaglione T, Fetoni AR, Pola E, Paludetti G, Michetti F, Lattanzi W To test the osteo-regenerative potential of adipose tissue-derived stromal cells (ATSCs), an attractive human source for tissue engineering, in a rat model of mandibular defect. Human dermal fibroblasts (HDFs) were used as a differentiated cellular control in the study. PMID: 21576557 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of Oxidative Stress Status during Diabetic Bone Healing. Cells Tissues Organs. 2011 May 13; Authors: Waddington RJ, Alraies A, Colombo JS, Sloan AJ, Okazaki J, Moseley R Early events associated with bone healing in patients with type 2 diabetes mellitus appear to be delayed. Hyperglycaemia and an associated increase in oxidative stress are cited as potential factors leading to a change in cellular behaviour. Using an in vivo model monitoring bone formation around implants placed into rat mandibles, we have previously identified that the onset of cell proliferation and osteoblast differentiation are delayed and subsequently prolonged compared with normal bone. This study used the same implant model to characterize oxidative stress biomarkers and primary antioxidant enzyme profiles during diabetic bone healing in vivo. Implants were placed into the sockets of incisors extracted from the mandibles of normal Wistar and diabetic Goto-Kakizaki rats for 3 and 9 weeks after implant insertion. Histochemical analysis confirmed a delay in bone healing around implants in diabetic animals. Immunohistochemical localization of peri-cellular staining for protein carbonyl groups, as a biomarker of oxidized protein content, was slightly higher in diabetic granulation tissue compared with normal tissue. However, no differences were observed in the staining patterns of advanced glycation end products. Minimal differences were observed in the number of cells positive for cytoplasmic superoxide dismutase (SOD)1 or mitochondrial SOD2. Significantly, catalase was absent in diabetic tissues. The results suggest that the oxidative environment in healing bone is differentially affected by hyperglycaemia, particularly in relation to catalase. The significance of these observations for diabetic bone healing is discussed. PMID: 21576908 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Effect of coating Straumann® Bone Ceramic with Emdogain on mesenchymal stromal cell hard tissue formation. Clin Oral Investig. 2011 May 17; Authors: Mrozik KM, Gronthos S, Menicanin D, Marino V, Bartold PM Periodontal tissue engineering requires a suitable biocompatible scaffold, cells with regenerative capacity, and instructional molecules. In this study, we investigated the capacity of Straumann® Bone Ceramic coated with Straumann® Emdogain, a clinical preparation of enamel matrix protein (EMP), to aid in hard tissue formation by post-natal mesenchymal stromal cells (MSCs) including bone marrow stromal cells (BMSCs) and periodontal ligament fibroblasts (PDLFs). MSCs were isolated and ex vivo-expanded from human bone marrow and periodontal ligament and, in culture, allowed to attach to Bone Ceramic in the presence or absence of Emdogain. Gene expression of bone-related proteins was investigated by real time RT-PCR for 72 h, and ectopic bone formation was assessed histologically in subcutaneous implants of Bone Ceramic containing MSCs with or without Emdogain in NOD/SCID mice. Alkaline phosphatase activity was also assessed in vitro, in the presence or absence of Emdogain. Collagen-I mRNA was up-regulated in both MSC populations over the 72-h time course with Emdogain. Expression of BMP-2 and the osteogenic transcription factor Cbfa-1 showed early stimulation in both MSC types after 24 h. In contrast, expression of BMP-4 was consistently down-regulated in both MSC types with Emdogain. Up-regulation of osteopontin and periostin mRNA was restricted to BMSCs, while higher levels of bone sialoprotein-II were observed in PDLFs with Emdogain. Furthermore, alkaline phosphatase activity levels were reduced in both BMSCs and PDLFs in the presence of Emdogain. Very little evidence was found for ectopic bone formation following subcutaneous implantation of MSCs with Emdogain-coated or -uncoated Bone Ceramic in NOD/SCID mice. The early up-regulation of several important bone-related genes suggests that Emdogain may have a significant stimulatory effect in the commitment of mesenchymal cells to osteogenic differentiation in vitro. While Emdogain inhibited AP activity and appeared not to induce ectopic bone formation, longer-term studies are required to determine whether it promotes the final stages of osteoblast formation and mineralization at gene and protein levels. While used in clinical applications, whether Emdogain and other commercial preparations of EMPs truly possess the capacity to induce the regeneration of bone or other components of the periodontium remains to be established. PMID: 21584694 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | DEVELOPMENT OF GELLAN-GUM BASED MICROPARTICLES/HYDROGEL MATRICES FOR APPLICATION IN THE INTERVERTEBRAL DISC REGENERATION. Tissue Eng Part C Methods. 2011 May 17; Authors: Pereira DR, Silva-Correia J, Caridade SG, Oliveira JT, Sousa RA, Salgado A, Oliveira JM, Mano J, Sousa N, Reis RL Low back pain is one of the most reported medical conditions associated to intervertebral disc (IVD) degeneration. Nucleus pulposus (NP) is often regarded as the structure where intervertebral disc degeneration begins. Gellan gum-based (GG) hydrogels for acellular and cellular tissue engineering strategies have been developed for finding applications as NP substitutes. The innovative strategy is based on the reinforcement of the hydrogel matrix with biocompatible and biodegradable GG microparticles (MPs), which are expected to improve the mechanical properties, while allowing to tailor its degradation rate. In this study, several GG MPs/hydrogels discs formulations were prepared by means of mixing high (HAGG 0.75% (w/v)) and low acyl (LAGG 2% (w/v)) GG aqueous solutions at different ratios, namely 75%:25% (v/v), 50%:50% (v/v), 25%:75% (v/v), respectively. The GG MPs size was measured using a stereo microscope and their dispersion within the hydrogel matrix was evaluated by means of staining the MPs with Toluidine Blue-O. The developed GG MPs/hydrogel discs were physico-chemically characterized by Fourier-transform infrared spectroscopy and 1H-nuclear magnetic resonance spectroscopy. The swelling behaviour and degradation rate were assessed by immersion in a phosphate buffer saline solution for the period of 14 days. The morphology and mechanical behaviour were investigated by scanning electron microscopy and dynamic mechanical analysis, respectively. The mechanical properties of the hydrogels discs were improved by mixing the gels with the MPs. In addition, the possible cytotoxicity of the leachables released by MPs/hydrogel discs was screened in vitro, using a mouse lung fibroblast cell line (L929 cells). In order to investigate the encapsulation efficacy of L929 cells into the GG MPs/hydrogel discs, cells were stained with DAPI blue/Texas Red-Phalloidin and observed by confocal microscopy, after 24, 48 and 72 hours of culturing. A cell viability assay was also performed using Calcein AM staining. The cell culture studies demonstrated that MPs/hydrogel discs are non-cytotoxic over L929 cells. It was also demonstrated that L929 cells can be successfully encapsulated into the GG MPs of different formulations, remaining viable after 72 hours of culturing. This study showed that GG hydrogel matrices reinforced with cell-loaded MPs could be a candidate strategy for NP regeneration. PMID: 21574937 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Facile Synthesis of Degradable and Electrically Conductive Polysaccharide Hydrogels. Biomacromolecules. 2011 May 16; Authors: Guo B, Finne-Wistrand A, Albertsson AC Degradable and electrically conductive polysaccharide hydrogels (DECPHs) have been synthesised by functionalizing polysaccharide with conductive aniline oligomers. DECPHs based on chitosan (CS), aniline tetramer (AT), and glutaraldehyde were obtained by a facile one-pot reaction by using the amine group of CS and AT under mild conditions, which avoids the multi-step reactions and tedious purification involved in the synthesis of degradable conductive hydrogels in our previous work. Interestingly, these one-pot hydrogels possess good film-forming properties, electrical conductivity and a pH-sensitive swelling behaviour. The chemical structure and morphology before and after swelling of the hydrogels were verified by FT-IR, NMR and SEM. The conductivity of the hydrogels was tuned by adjusting the content of AT. The swelling ratio of the hydrogels was altered by the content of tetraaniline and crosslinker. The hydrogels underwent slow degradation in a buffer solution. The hydrogels obtained by this facile approach provide new possibilities in biomedical applications, e.g. biodegradable conductive hydrogels, films and scaffolds for cardiovascular tissue engineering and controlled drug delivery. PMID: 21574634 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Synthesis, biophysical properties, and oxygenation potential of variable molecular weight glutaraldehyde-polymerized bovine hemoglobins with low and high oxygen affinity. Biotechnol Prog. 2011 Apr 20; Authors: Zhou Y, Jia Y, Buehler PW, Chen G, Cabrales P, Palmer AF In a recent study, ultrahigh molecular weight (M(w) ) glutaraldehyde-polymerized bovine hemoglobins (PolybHbs) were synthesized with low O(2) affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top-load model.(1) In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O(2) affinity state. Our results showed that the M(w) of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O(2) affinity PolybHbs, increasing the G:Hb molar ratio reduced the O(2) affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O(2) affinity PolybHbs, increasing the G:Hb molar ratio led to increased O(2) affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O(2) affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O(2) affinity PolybHbs to potentially oxygenate tissues in vivo, an O(2) transport model was used to simulate O(2) transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O(2) affinity PolybHbs oxygenated the bioreactor better than high O(2) affinity PolybHbs. This result points to the suitability of low O(2) affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin-based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011. PMID: 21584950 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Therapeutic potential of lung epithelial progenitor cells derived from embryonic and induced pluripotent stem cells. Annu Rev Med. 2011 Feb 18;62:95-105 Authors: Wetsel RA, Wang D, Calame DG Embryonic stem (ES) cells derived from preimplantation blastocysts and induced pluripotent stem (iPS) cells generated from somatic cell sources are pluripotent and capable of indefinite expansion in vitro. They provide a possible unlimited source of cells that could be differentiated into lung progenitor cells for potential clinical use in pulmonary regenerative medicine. Because of inherent difficulties in deriving endodermal cells from undifferentiated cell cultures, applications using lung epithelial cells derived from ES and iPS cells have lagged behind similar efforts devoted to other tissues, such as the heart and spinal cord. However, during the past several years, significant advances in culture, differentiation, and purification protocols, as well as in bioengineering methodologies, have fueled enthusiasm for the development of stem cell-based lung therapeutics. This article provides an overview of recent research achievements and discusses future technical challenges that must be met before the promise of stem cell applications for lung disease can be realized. PMID: 21226612 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Prenatally harvested cells for cardiovascular tissue engineering: Fabrication of autologous implants prior to birth. Placenta. 2011 May 14; Authors: Weber B, Zeisberger SM, Hoerstrup SP Using the principal of tissue engineering, several groups have demonstrated the feasibility of creating heart valves, blood vessels, and myocardial structures using autologous cells and biodegradable scaffold materials. In the current cardiovascular clinical scenario, the main medical need for a tissue engineering solution is in the field of pediatric applications treating congenital heart disease. In these young patients, the introduction of autologous viable and growing replacement structures, such as tissue engineered heart valves and vessels, would substantially reduce today's severe therapeutic limitations, which are mainly due to the need for repeat reoperations to adapt the current artificial prostheses to somatic growth. Based on high resolution imaging techniques, an increasing number of defects are diagnosed already prior to birth around week 20. For interventions, cells should be obtained already during pregnancy to provide tissue engineered implants either at birth or even prenatally. In our recent studies human fetal mesenchymal stem cells were isolated from routinely sampled prenatal amniotic fluid or chorionic villus specimens and expanded in vitro. Fresh and cryopreserved samples were used. After phenotyping and genotyping, cells were seeded onto synthetic biodegradable scaffolds and conditioned in a bioreactor. Leaflets were endothelialized with either amniotic fluid- or umbilical cord blood-derived endothelial progenitor cells and conditioned. Resulting tissues were analyzed by histology, immunohistochemistry, biochemistry (amounts of extracellular matrix, DNA), mechanical testing, and scanning electron microscopy (SEM) and were compared with native neonatal heart valve leaflets. Genotyping confirmed their fetal origin, and fresh versus cryopreserved cells showed comparable myofibroblast-like phenotypes. Neo-tissues exhibited organization, cell phenotypes, extracellular matrix production, and DNA content comparable to their native counterparts. Leaflet surfaces were covered with functional endothelia. SEM showed morphologically cellular distribution throughout the polymer and smooth surfaces. Mechanical profiles approximated those of native heart valves. These in vitro studies demonstrated the principal feasibility of using various human cell types isolated from fetal sources for cardiovascular tissue engineering. Umbilical cord blood-, amniotic fluid- and chorionic villi-derived cells have shown promising potential for the clinical realization of this congenital tissue engineering approach. Based on these results, future research must aim at further investigation as well as preclinical evaluation of prenatally harvested stem- or progenitor cells with regard to their potential for clinical use. PMID: 21575988 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Polymer-based microparticles in tissue engineering and regenerative medicine. Biotechnol Prog. 2011 Mar 30; Authors: Oliveira MB, Mano JF Different types of biomaterials, processed into different shapes, have been proposed as temporary support for cells in tissue engineering (TE) strategies. The manufacturing methods used in the production of particles in drug delivery strategies have been adapted for the development of microparticles in the fields of TE and regenerative medicine (RM). Microparticles have been applied as building blocks and matrices for the delivery of soluble factors, aiming for the construction of TE scaffolds, either by fusion giving rise to porous scaffolds or as injectable systems for in situ scaffold formation, avoiding complicated surgery procedures. More recently, organ printing strategies have been developed by the fusion of hydrogel particles with encapsulated cells, aiming the production of organs in in vitro conditions. Mesoscale self-assembly of hydrogel microblocks and the use of leachable particles in three-dimensional (3D) layer-by-layer (LbL) techniques have been suggested as well in recent works. Along with innovative applications, new perspectives are open for the use of these versatile structures, and different directions can still be followed to use all the potential that such systems can bring. This review focuses on polymeric microparticle processing techniques and overviews several examples and general concepts related to the use of these systems in TE and RE applications. The use of materials in the development of microparticles from research to clinical applications is also discussed. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011. PMID: 21584949 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Comparison of Chondrogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells with Cultured Chondrocytes and Bone Marrow Mesenchymal Stem Cells.] Acta Chir Orthop Traumatol Cech. 2011;78(2):138-144 Authors: Havlas V, Kos P, Jendelová P, Lesný P, Trč T, Syková E PURPOSE OF THE STUDY Many congenital and acquired disorders as well as sequelae of injury are associated with articular cartilage degenera- tion, which adversely affects the patient's quality of life. The currently used cell therapy with cultured chondrocytes has its disadvantages due to a process of de-differentiation of chondrocytes during cultivation. We believe that the mesenchymal stem cell therapy offers a new treatment options. MATERIAL AND METHODS The adult mesenchymal stem cells (MSCs) for chondrocyte differentiation are usually obtained from bone marrow mesen- chymal stem cells (BMSCs). In this study these cells were compared with mesenchymal stem cells derived from adipose tissue (AMSCs). The aim of the study was to verify the ability of human BMSCs and AMSCs to differentiate into chondro- cytes in vitro in the presence or absence of transforming growth factor beta (TGF-ß1). Human BMSCs and AMSCs were collected from healthy donors during orthopaedic surgeries, in vitro cultured in three passages to obtain the required quan- tity of cells. A pellet culture system was used for chondrocyte differentiation. RESULTS At 21 days of cultivation, cell aggregates grown in the chondrogenic medium were larger than those cultured in the con- trol medium. Both the BMSCs and AMSCs pellet cultures showed spontaneous chondrogenesis. Histological staining with haematoxylin and eosin and Masson's trichrome stains, as well as immunohistochemical staining to detect type II collagen revealed no apparent differences between the pellet cultures with TGF-ß1 presence and those without it. The real-time RT-PCR detected expression of the type II collagen gene in all tested cultures. In the BMSCs pellet culture only, TGF-ß1 presence resulted in a decrease in type I collagen mRNA levels and in an increase in type II collagen mRNA values. DISCUSSION Our results showed an in vitro chondrogenic potential of mature human mesenchymal stem cells derived from both bone marrow and adipose tissue. In agreement with the relevant literature data, we suggest that both cell types have an equal prospect for use in cartilage tissue engineering. Key words: bone marrow, adipose tissue, transforming growth factor beta, cartilage, pellet culture system. PMID: 21575557 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | [Tissue integration of various silicone-coated polypropylene surgical mesh]. Magy Seb. 2010 Oct;63(5):340-6 Authors: Takács I, Horváth S, Balatonyi B, Jávor S, Molnár A, Gáspár S, Hajós R, Meczker A, Lantos J, Roth E, Wéber G Laparoscopic ventral hernia repair requires a surgical mesh implanted in intraperitoneal position. The combined, double layer meshes are promising in animal models as well as in human practice. The aim of this study was to compare the biological behaviour of two different textured silicone covered polypropylene mesh. PMID: 20965868 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | Robert Klein, chairman of the $3 billion California Institute for Regenerative Medicine, is backing the head of a Southern California investment firm to succeed him at the helm of CIRM as it pushes aggressively to bring stem cell therapies into the marketplace, according to a reliable source.
However, James Harrison, outside counsel to the CIRM board, flatly denied that Klein has endorsed any | | | | | | | | | | | | | | | | | | | | | | | | | Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway. Breast Cancer Res Treat. 2011 May 17; Authors: Yan XL, Fu CJ, Chen L, Qin JH, Zeng Q, Yuan HF, Nan X, Chen HX, Zhou JN, Lin YL, Zhang XM, Yu CZ, Yue W, Pei XT Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway. PMID: 21584665 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Polymer-based microparticles in tissue engineering and regenerative medicine. Biotechnol Prog. 2011 Mar 30; Authors: Oliveira MB, Mano JF Different types of biomaterials, processed into different shapes, have been proposed as temporary support for cells in tissue engineering (TE) strategies. The manufacturing methods used in the production of particles in drug delivery strategies have been adapted for the development of microparticles in the fields of TE and regenerative medicine (RM). Microparticles have been applied as building blocks and matrices for the delivery of soluble factors, aiming for the construction of TE scaffolds, either by fusion giving rise to porous scaffolds or as injectable systems for in situ scaffold formation, avoiding complicated surgery procedures. More recently, organ printing strategies have been developed by the fusion of hydrogel particles with encapsulated cells, aiming the production of organs in in vitro conditions. Mesoscale self-assembly of hydrogel microblocks and the use of leachable particles in three-dimensional (3D) layer-by-layer (LbL) techniques have been suggested as well in recent works. Along with innovative applications, new perspectives are open for the use of these versatile structures, and different directions can still be followed to use all the potential that such systems can bring. This review focuses on polymeric microparticle processing techniques and overviews several examples and general concepts related to the use of these systems in TE and RE applications. The use of materials in the development of microparticles from research to clinical applications is also discussed. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011. PMID: 21584949 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Histone H4K20me3 and HP1{alpha} are late heterochromatin markers in development, but present in undifferentiated embryonic stem cells. J Cell Sci. 2011 Jun 1;124(Pt 11):1878-90 Authors: Wongtawan T, Taylor JE, Lawson KA, Wilmut I, Pennings S We report here that the formation of heterochromatin in cell nuclei during mouse development is characterised by dynamic changes in the epigenetic modifications of histones. Our observations reveal that heterochromatin in mouse preimplantation embryos is in an immature state that lacks the constitutive heterochromatin markers histone H4 trimethyl Lys20 (H4K20me3) and chromobox homolog 5 (HP1α, also known as CBX5). Remarkably, these somatic heterochromatin hallmarks are not detectable - except in mural trophoblast - until mid-gestation, increasing in level during foetal development. Our results support a developmentally regulated connection between HP1α and H4K20me3. Whereas inner cell mass (ICM) and epiblast stain negative for H4K20me3 and HP1α, embryonic stem (ES) cell lines, by contrast, stain positive for these markers, indicating substantial chromatin divergence. We conclude that H4K20me3 and HP1α are late developmental epigenetic markers, and slow maturation of heterochromatin in tissues that develop from ICM is ectopically induced during ES cell derivation. Our findings suggest that H4K20me3 and HP1α are markers for cell type commitment that can be triggered by developmental or cell context, independently of the differentiation process. PMID: 21576353 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | [Comparison of Chondrogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells with Cultured Chondrocytes and Bone Marrow Mesenchymal Stem Cells.] Acta Chir Orthop Traumatol Cech. 2011;78(2):138-144 Authors: Havlas V, Kos P, Jendelová P, Lesný P, Trč T, Syková E PURPOSE OF THE STUDY Many congenital and acquired disorders as well as sequelae of injury are associated with articular cartilage degenera- tion, which adversely affects the patient's quality of life. The currently used cell therapy with cultured chondrocytes has its disadvantages due to a process of de-differentiation of chondrocytes during cultivation. We believe that the mesenchymal stem cell therapy offers a new treatment options. MATERIAL AND METHODS The adult mesenchymal stem cells (MSCs) for chondrocyte differentiation are usually obtained from bone marrow mesen- chymal stem cells (BMSCs). In this study these cells were compared with mesenchymal stem cells derived from adipose tissue (AMSCs). The aim of the study was to verify the ability of human BMSCs and AMSCs to differentiate into chondro- cytes in vitro in the presence or absence of transforming growth factor beta (TGF-ß1). Human BMSCs and AMSCs were collected from healthy donors during orthopaedic surgeries, in vitro cultured in three passages to obtain the required quan- tity of cells. A pellet culture system was used for chondrocyte differentiation. RESULTS At 21 days of cultivation, cell aggregates grown in the chondrogenic medium were larger than those cultured in the con- trol medium. Both the BMSCs and AMSCs pellet cultures showed spontaneous chondrogenesis. Histological staining with haematoxylin and eosin and Masson's trichrome stains, as well as immunohistochemical staining to detect type II collagen revealed no apparent differences between the pellet cultures with TGF-ß1 presence and those without it. The real-time RT-PCR detected expression of the type II collagen gene in all tested cultures. In the BMSCs pellet culture only, TGF-ß1 presence resulted in a decrease in type I collagen mRNA levels and in an increase in type II collagen mRNA values. DISCUSSION Our results showed an in vitro chondrogenic potential of mature human mesenchymal stem cells derived from both bone marrow and adipose tissue. In agreement with the relevant literature data, we suggest that both cell types have an equal prospect for use in cartilage tissue engineering. Key words: bone marrow, adipose tissue, transforming growth factor beta, cartilage, pellet culture system. PMID: 21575557 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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