| Lineage Enforcement by Inductive Mesenchyme on Adult Epithelial Stem Cells across Developmental Germ Layers.
October 29, 2009 at 8:11 am
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| | Lineage Enforcement by Inductive Mesenchyme on Adult Epithelial Stem Cells across Developmental Germ Layers. Stem Cells. 2009 Oct 27; Authors: Taylor RA, Wang H, Wilkinson SE, Richards MG, Britt K, Vaillant F, Lindeman GJ, Visvader JE, Cunha GR, St John J, Risbridger GP During development, cell differentiation is accompanied by the progressive loss of pluripotent gene expression and developmental potential, although de-differentiation in specialized cells can be induced by reprogramming strategies indicating that transdifferentiation potential is retained in adult cells. The stromal niche provides differentiating cues to epithelial stem cells (SCs), but current evidence is restricted to tissue types within the same developmental germ layer lineage. Anticipating the use of adult SCs for tissue regeneration, we examined if stroma can enforce lineage commitment across germ layer boundaries and promote transdifferentiation of adult epithelial SCs. Here, we report tissue-specific mesenchyme instructing epithelial cells from a different germ layer origin to express dual phenotypes. Prostatic stroma induced mammary epithelia (or enriched Lin(-)CD29(HI)CD24(+/MOD) mammary SCs) to generate glandular epithelia expressing both prostatic and mammary markers such as steroid hormone receptors and transcription factors including Foxa1, Nkx3.1 and GATA-3. Array data implicated Hh and Wnt pathways in mediating stromal-epithelial interactions (validated by increased Cyclin D1 expression). Other recombinants of prostatic mesenchyme and skin epithelia, or preputial gland mesenchyme and bladder or esophageal epithelia, showed foci expressing new markers adjacent to the original epithelial differentiation (e.g. sebaceous cells within bladder urothelium), confirming altered lineage specification induced by stroma and evidence of cross-germ layer transdifferentiation. Thus, stromal cell niche is critical in maintaining (or re-directing) differentiation in adult epithelia. In order to use adult epithelial SCs in regenerative medicine, we must additionally regulate their intrinsic properties to prevent (or enable) transdifferentiation in specified SC niches. PMID: 19862839 [PubMed - as supplied by publisher] |
| DNA methylation is a guardian of stem cell self-renewal and multipotency.
October 29, 2009 at 8:11 am
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| | DNA methylation is a guardian of stem cell self-renewal and multipotency. Nat Genet. 2009 Nov;41(11):1164-6 Authors: Gereige LM, Mikkola HK Epigenetic marks, such as DNA methylation and histone modifications, undergo dynamic changes during cellular differentiation and development. A new study demonstrates that DNA methylation by Dnmt1 protects essential stem cell properties in both hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) by silencing differentiation programs that interfere with self-renewal and multipotency. PMID: 19862008 [PubMed - in process] |
| Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee: A Prospective Clinical Case Series With 2 to 7 Years' Follow-up.
October 29, 2009 at 8:11 am
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| | Treatment of Full-Thickness Chondral Defects With Hyalograft C in the Knee: A Prospective Clinical Case Series With 2 to 7 Years' Follow-up. Am J Sports Med. 2009 Oct 27; Authors: Nehrer S, Dorotka R, Domayer S, Stelzeneder D, Kotz R BACKGROUND: Tissue engineering has become available for cartilage repair in clinical practice. HYPOTHESIS: The treatment of full-thickness chondral defects in the knee with a hyaluronan-based scaffold seeded with autologous chondrocytes provides stable improvement of clinical outcome up to 7 years. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Fifty-three patients with deep osteochondral defects in the knee were treated with Hyalograft C. The mean age at implantation was 32 +/- 12 years, the mean defect size was 4.4 +/- 1.9 cm(2), and the mean body mass index was 24.5 +/- 3.8 kg/m(2). Implantations were performed with miniarthrotomy or arthroscopy. The primary indications for implantation with Hyalograft C included young patients with a stable joint, normal knee alignment, and isolated chondral defects with otherwise healthy adjacent cartilage. The secondary indications were patients who did not meet the primary indication criteria or were salvage procedures. Forty-two patients with primary indications and 11 patients with secondary indications were evaluated. Outcome was evaluated with the International Cartilage Repair Society and International Knee Documentation Committee scales, the Lysholm score, the modified Cincinnati score, and with Kaplan-Meier survival analysis. Statistical analysis consisted of bivariate correlation analysis and unpaired, 2-tailed t tests. RESULTS: A highly significant increase (P < .001) in all knee scores was found in patients treated for the primary indications. Nine of 11 secondary indication cases underwent total knee arthroplasty due to persisting pain between 2 and 5 years after implantation. Graft failure occurred in 3 of 42 patients with primary indication between 6 months and 5 years after implantation. Kaplan-Meier survival demonstrated significantly different chances for survival between primary and secondary outcome and between simple, complex, and salvage cases, respectively (P < .001). CONCLUSION: Hyalograft C autograft provides clinical improvement in healthy young patients with single cartilage defects. Less complicated surgery and lower morbidity are considered advantages of the technique. The results of treatment with Hyalograft C as a salvage procedure or in patients with osteoarthritis are poor. PMID: 19861701 [PubMed - as supplied by publisher] |
| Matrix-Assisted Autologous Chondrocyte Transplantation for the Repair of Cartilage Defects of the Knee: Systematic Clinical Data Review and Study Quality Analysis.
October 29, 2009 at 8:11 am
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| | Matrix-Assisted Autologous Chondrocyte Transplantation for the Repair of Cartilage Defects of the Knee: Systematic Clinical Data Review and Study Quality Analysis. Am J Sports Med. 2009 Oct 27; Authors: Kon E, Verdonk P, Condello V, Delcogliano M, Dhollander A, Filardo G, Pignotti E, Marcacci M BACKGROUND: The clinical application of the second-generation tissue-engineering approach for the treatment of cartilage lesions has been documented for different types of scaffolds, but systematic information on clinical efficacy and long-term results is not available. PURPOSE: To analyze and assess the quality of clinical studies on different products in the emerging field of matrix-assisted autologous chondrocyte transplantation. The secondary purpose of this review was to improve the quality assessment of studies by modifying the Coleman methodology score (CMS). STUDY DESIGN: Systematic review. METHODS: For this review, a literature search was performed to identify all published and unpublished clinical studies of matrix-assisted (second-generation) autologous chondrocyte transplantation using the following medical electronic databases: MEDLINE, MEDLINE preprints, EMBASE, CINAHL, Life Science Citations, and British National Library of Health, including the Cochrane Central Register of Controlled Trials (CENTRAL). The search period was January 1, 1995, to July 1, 2008. To better assess cartilage-related studies, a modification of the CMS was proposed. RESULTS: Eighteen studies were included in the analysis, reporting on 731 patients with an average follow-up of 27.3 months (6.5-60.0 months). Of the 18 studies, 2 were randomized controlled studies, 3 were prospective comparative studies, 11 were prospective cohort studies or prospective case series, and 2 were retrospective case series. Original CMSs for these studies (55.1 +/- 1.6) were significantly higher than those of cartilage repair studies in general (43.5 +/- 1.6, P < .0001) reported in 2005. The statistical analysis indicated that the modified CMS showed higher correlations and lower variability of correlations among 3 reviewers. CONCLUSION: The quality of the currently available data on second-generation autologous chondrocyte transplantation is still limited by study designs. The modified CMS has demonstrated better sensitivity and reproducibility with respect to the original score, so it can be recommended for cartilage clinical studies evaluation. PMID: 19861700 [PubMed - as supplied by publisher] |
| Nano-sized and nanocrystalline calcium orthophosphates.
October 29, 2009 at 8:11 am
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| | Nano-sized and nanocrystalline calcium orthophosphates. Acta Biomater. 2009 Oct 24; Authors: Dorozhkin SV Recent developments in biomineralization have already demonstrated that nano-sized crystals and particles play an important role in the formation of hard tissues of animals. Namely, it is well established that the basic inorganic building blocks of bones and teeth of mammals are nano-sized and nanocrystalline calcium orthophosphates in the form of apatites. In mammals, tens to hundreds nanocrystals of a biological apatite have been found to be combined into self-assembled structures under the control of bioorganic matrixes. Therefore, application and prospective use of the nano-sized and nanocrystalline calcium orthophosphates for a clinical repair of damaged bones and teeth are also well known. For example, a greater viability and a better proliferation of various types of cells have been detected on smaller crystals of calcium orthophosphates. Thus, the nano-sized and nanocrystalline forms of calcium orthophosphates have a great potential to revolutionize the hard tissue-engineering field, starting from bone repair and augmentation to the controlled drug delivery systems. This paper reviews current state-of-art and recent developments of various nano-sized and nanocrystalline calcium orthophosphates, starting from the synthesis and characterization to the biomedical and clinical applications. Besides, the review provides possible directions of future research and development. PMID: 19861183 [PubMed - as supplied by publisher] |
| Effect of chitosan scaffold microstructure on mesenchymal stem cells chondrogenesis.
October 29, 2009 at 8:11 am
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| | Effect of chitosan scaffold microstructure on mesenchymal stem cells chondrogenesis. Acta Biomater. 2009 Oct 24; Authors: Ragetly GR, Griffon DJ, Lee HB, Fredericks LP, Gordon-Evans W, Chung YS Although numerous biomaterials have been investigated as scaffolds for cartilage tissue engineering, the effect of their microstructure on final construct characteristics remains unclear. The biocompatibility of chitosan and its similarity with glycosaminoglycans make it attractive as a scaffold for cartilage engineering. Our objective was to evaluate the effect of chitosan scaffold structure on mesenchymal stem cell proliferation and chondrogenesis. Chitosan fibrous scaffolds and chitosan sponges were seeded with mesenchymal stem cells in a chondrogenic medium. Constructs were analyzed 72 hours after seeding via scanning electron microscopy (SEM), weight measurements and DNA quantification. Constructs were cultured for 10 or 21 days prior to confocal microscopy, SEM, histology, quantitive analysis (weight, DNA, and glycosaminoglycan (GAG)), and quantitative real time polymerase chain reaction. Mesenchymal stem cells maintained a viability above 90% on all chitosan scaffolds. The cell numbers in the constructs were similar at 72 hours, 10 days and 21 days. However, matrix production was improved in chitosan fibrous constructs based on the GAG quantification and Collagen II mRNA expression. Chondrogenesis on chitosan scaffolds is superior on microfibers compared to macroporous sponges. PMID: 19861178 [PubMed - as supplied by publisher] |
| In vitro small intestinal epithelial cell growth on a nanocomposite polycaprolactone scaffold.
October 29, 2009 at 8:11 am
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| | In vitro small intestinal epithelial cell growth on a nanocomposite polycaprolactone scaffold. Biotechnol Appl Biochem. 2009 Oct 27; Authors: Gupta A, Vara D, Punshon G, Sales K, Winslet M, Seifalian AM Tissue engineering of small intestine remains experimental despite worldwide attempts to develop a functional substitute for short bowel syndrome. Most published studies have reported predominant use of PLLA/ PGA copolymer as the scaffold material, and studies have been limited by in vivo experiments. This lack of progress has inspired a fresh perspective and provoked further investigation and development in this field of tissue engineering. In this paper we exploit a relatively new nanocomposite of polyhedral oligomeric silsesquixane (POSS) and polycaprolactone (PCL) as a material to develop porous scaffolds using a solvent casting/ particulate leaching technique to fabricate porous scaffolds in different pore sizes and porosities. Scaffolds were characterized for pore morphology and porosity using Scanning Electron Microscopy and Micro-CT. Rat intestinal epithelial cells were then seeded onto the polymer scaffolds for an in vitro study of cell compatibility and proliferation which was assessed by Alamar blue and LDH assays performed for 21 days post-seeding. The results obtained demonstrate that POSS-PCL nanocomposite was produced as a macro-porous scaffold with porosity in the range of 40-80% and pore size in the range of 150-250 microns. This scaffold was shown to support epithelial cell proliferation and growth. In conclusion, as a further step in investigating small intestinal tissue engineering the nanocomposite employed in this study may prove to be a useful alternative to PLGA in the future. PMID: 19860739 [PubMed - as supplied by publisher] |
| Down with the erythropoietin. Long live the erythropoietin!
October 29, 2009 at 8:11 am
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| | Down with the erythropoietin. Long live the erythropoietin! Curr Drug Targets. 2009 Oct;10(10):1028-32 Authors: Buemi M, Lacquaniti A, Bolignano D, Cernaro V, Campo S, Grasso G, Buemi A, Donato V, Sturiale A In recent years the use of erythropoietin has exploded, and the anaemia of patients with chronic renal failure has been practically resolved with the administration of rHuEpo (recombinant human, Erythropoietin). However, as a result of an intense commercial campaign, strong therapies with this growth hormone, prescribed to achieve surprising sporting performances, got athletes to run the risk of thrombosis and vascular accidents because of red blood cells increase. Erythropoietin represents a significant subject of research. In fact, besides the ability of stimulating erythrocyte production, it has many pleiotropic effects. Several studies allow the assertion that EPO, in different concentrations, has protective effects mainly on central nervous system and cardiovascular system through various mechanisms, among which a key role seems to be held by the ability to stimulate angiogenesis. The consequent problem is that anaemia therapy with rHuEpo in patients with cancer may accelerate the progression of neoplastic disease by promoting tumour angiogenesis and, thus, metastasization. The study of angiogenic process in tumours led to the synthesis of drugs that, blocking VEGF, exert an anti-angiogenic action, contrasting cancer spread. However, benefits are relatively modest. Is erythropoietin perhaps the further angiogenic hormone to block in tumour pathology? Therefore, Epo plays a role in Regenerative Medicine since it intervenes in a persistent natural regenerative activity of humans: angiogenesis. The understanding of the regeneration mechanisms of complex structures in the adult salamander has opened original lines of research. Regenerative Medicine tries to develop therapeutic pathways through the stimulation of natural regenerative processes in humans. PMID: 19860645 [PubMed - in process] |
| Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities.
October 29, 2009 at 8:11 am
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| | Periodontal Tissue Engineering and Regeneration: Current Approaches and Expanding Opportunities. Tissue Eng Part B Rev. 2009 Oct 27; Authors: Chen FM, Jin Y The management of periodontal tissue defects that result from periodontitis represents a medical and socioeconomic challenge. Concerted efforts have been and still are being made to accelerate and augment periodontal tissue and bone regeneration, including a range of regenerative surgical procedures, the development of a variety of grafting materials and the use of recombinant growth factors. More recently, tissue-engineering strategies including new cell- and/or matrix-based dimensions are also being developed, analysed and employed for periodontal regenerative therapies. Tissue engineering in periodontology applies the principles of engineering and life sciences toward the development of biological techniques that can restore lost alveolar bone, periodontal ligament and root cementum. It is based on an understanding of the role of periodontal formation and aims to grow new functional tissues rather than to build new replacements of periodontium. Whilst tissue engineering has merged to create more opportunities for predictable and optimal periodontal tissue regeneration, the technique and design for pre-clinical and clinical studies remain in their early stages. To date, the reconstruction of small- to moderate-sized periodontal bone defects using engineered cell-scaffold constructs is technically feasible, and some of the currently developed concepts may represent alternatives for certain ideal clinical scenarios. However, the predictable reconstruction of the normal structure and functionality of a tooth-supporting apparatus remains challenging. This review summarises current regenerative procedures for periodontal healing and regeneration and explores their progress and difficulties in clinical practice, with particular emphasis placed upon current challenges and future possibilities associated with tissue engineering strategies in periodontal regenerative medicine. PMID: 19860551 [PubMed - as supplied by publisher] |
| HLA-DRB1 among patients with Vogt-Koyanagi-Harada disease in Saudi Arabia.
October 29, 2009 at 8:11 am
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| | HLA-DRB1 among patients with Vogt-Koyanagi-Harada disease in Saudi Arabia. Mol Vis. 2009;15:1876-80 Authors: Iqniebi A, Gaafar A, Sheereen A, Al-Suliman A, Mohamed G, Al-Hussein K, Tabbara KF PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is an immune-mediated disorder with autoimmune insult directed against antigens associated with melanocytes. The genetic predisposition among VKH has not been explored in Saudi Arabia. So, the purpose of this study was to investigate the association of human leukocyte antigen (HLA)-DRB1 alleles to VKH patients and to clarify the molecular genetic mechanism underlying the susceptibility or resistance to VKH disease. METHODS: Genomic DNA from a total of 30 patients with VKH and 29 control subjects was extracted from peripheral blood, and HLA-DRB1 alleles were typed by polymerase chain reaction and sequence based typing (SBT). RESULTS: We found a statistically significant difference in the prevalence of HLA-DRB1 *0405 between the VKH patients and control subjects (p<0.05). Eleven out of thirty (36.6%) patients with VKH had positive HLA-DRB1 *0405 compared to two out of twenty-nine (6.9%) control subjects. However, there were no statistically significant differences in the HLA-DRB1 alleles *01, *0101, *0102, *0301, *04, *0403, *0404, *0701, *1001, *1101, *1112, *1301, *1302, *1303, *1501, and *1502 between the VKH patients and controls. CONCLUSIONS: Patients with VKH had significantly greater incidence of HLA-DRB1 *0405 when compared to age and sex-matched controls. Consequently, this finding suggests that HLA-DRB1 *0405 allele might play a role in the pathogenesis of VKH disease. PMID: 19756183 [PubMed - indexed for MEDLINE] |
| Generation of functional eyes from pluripotent cells.
October 29, 2009 at 8:11 am
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| | Generation of functional eyes from pluripotent cells. PLoS Biol. 2009 Aug;7(8):e1000174 Authors: Viczian AS, Solessio EC, Lyou Y, Zuber ME Pluripotent cells such as embryonic stem (ES) and induced pluripotent stem (iPS) cells are the starting point from which to generate organ specific cell types. For example, converting pluripotent cells to retinal cells could provide an opportunity to treat retinal injuries and degenerations. In this study, we used an in vivo strategy to determine if functional retinas could be generated from a defined population of pluripotent Xenopus laevis cells. Animal pole cells isolated from blastula stage embryos are pluripotent. Untreated, these cells formed only epidermis, when transplanted to either the flank or eye field. In contrast, misexpression of seven transcription factors induced the formation of retinal cell types. Induced retinal cells were committed to a retinal lineage as they formed eyes when transplanted to the flanks of developing embryos. When the endogenous eye field was replaced with induced retinal cells, they formed eyes that were molecularly, anatomically, and electrophysiologically similar to normal eyes. Importantly, induced eyes could guide a vision-based behavior. These results suggest the fate of pluripotent cells may be purposely altered to generate multipotent retinal progenitor cells, which differentiate into functional retinal cell classes and form a neural circuitry sufficient for vision. PMID: 19688031 [PubMed - indexed for MEDLINE] |
| Strategies for retinal repair: cell replacement and regeneration.
October 29, 2009 at 8:11 am
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| | Strategies for retinal repair: cell replacement and regeneration. Prog Brain Res. 2009;175:23-31 Authors: Lamba DA, Karl MO, Reh TA The retina, like most other regions of the central nervous system, is subject to degeneration from both genetic and acquired causes. Once the photoreceptors or inner retinal neurons have degenerated, they are not spontaneously replaced in mammals. In this review, we provide an overview of retinal development and regeneration with emphasis on endogenous repair and replacement seen in lower vertebrates and recent work on induced mammalian retinal regeneration from Müller glia. Additionally, recent studies demonstrating the potential for cellular replacement using postmitotic photoreceptors and embryonic stem cells are also reviewed. PMID: 19660646 [PubMed - indexed for MEDLINE] |
| A comparison before and after aprotinin was suspended in cardiac surgery: different results in the real world from a single cardiac center in China.
October 29, 2009 at 8:11 am
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| | A comparison before and after aprotinin was suspended in cardiac surgery: different results in the real world from a single cardiac center in China. J Thorac Cardiovasc Surg. 2009 Oct;138(4):897-903 Authors: Wang X, Zheng Z, Ao H, Zhang S, Wang Y, Zhang H, Li L, Hu S OBJECTIVE: Use of aprotinin has been suspended in cardiac surgery since recent studies reported its risks associated with mortality and other adverse events. This study was to investigate the safety and efficacy of aprotinin through a comparison before and after aprotinin was suspended in cardiac surgery. METHODS: We designed a case-control study in two groups of patients who underwent cardiac surgery just before and after aprotinin was suspended in China. The aprotinin group (n = 1699) was defined as operations performed from June 19, 2007, to December 18, 2007, when aprotinin was used in all the patients. The control group (n = 2225) was defined as operations performed from December 19, 2007, to June 18, 2008, when aprotinin was not used. We compared early postoperative outcomes between the two groups. RESULTS: The aprotinin group had less postoperative blood loss, transfusion requirement, and reoperation for bleeding. Application of aprotinin did not increase the risk of in-hospital mortality (0.5% vs 1.0%; P = .08) and other major adverse outcome events, including renal, cardiac, neurologic, and pulmonary complications. The aprotinin group had a shorter mechanical ventilation time (P = .04), a lower rate of delayed mechanical ventilation time (P = .04), and a higher arterial oxygen tension/inspired oxygen fraction ratio in arterial blood gas analysis (P < .001). Multivariable logistic regression analysis confirmed findings from univariate analysis. After propensity adjustment for the baseline characteristics, we obtained similar results. CONCLUSIONS: Use of aprotinin in cardiac surgery could reduce blood loss and transfusion requirement significantly and showed a protective effect on the lungs, but it did not increase the risk of mortality or major complications. PMID: 19660368 [PubMed - indexed for MEDLINE] |
| Engineered 3D tissue models for cell-laden microfluidic channels.
October 29, 2009 at 8:11 am
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| | Engineered 3D tissue models for cell-laden microfluidic channels. Anal Bioanal Chem. 2009 Sep;395(1):185-93 Authors: Song YS, Lin RL, Montesano G, Durmus NG, Lee G, Yoo SS, Kayaalp E, Haeggström E, Khademhosseini A, Demirci U Delivery of nutrients and oxygen within three-dimensional (3D) tissue constructs is important to maintain cell viability. We built 3D cell-laden hydrogels to validate a new tissue perfusion model that takes into account nutrition consumption. The model system was analyzed by simulating theoretical nutrient diffusion into cell-laden hydrogels. We carried out a parametric study considering different microchannel sizes and inter-channel separation in the hydrogel. We hypothesized that nutrient consumption needs to be taken into account when optimizing the perfusion channel size and separation. We validated the hypothesis by experiments. We fabricated circular microchannels (r = 400 microm) in 3D cell-laden hydrogel constructs (R = 7.5 mm, volume = 5 ml). These channels were positioned either individually or in parallel within hydrogels to increase nutrient and oxygen transport as a way to improve cell viability. We quantified the spatial distribution of viable cells within 3D hydrogel scaffolds without channels and with single- and dual-perfusion microfluidic channels. We investigated quantitatively the cell viability as a function of radial distance from the channels using experimental data and mathematical modeling of diffusion profiles. Our simulations show that a large-channel radius as well as a large channel to channel distance diffuse nutrients farther through a 3D hydrogel. This is important since our results reveal that there is a close correlation between nutrient profiles and cell viability across the hydrogel. PMID: 19629459 [PubMed - indexed for MEDLINE] |
| A neurosurgeon's guide to stem cells, cancer stem cells, and brain tumor stem cells.
October 29, 2009 at 8:11 am
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| | A neurosurgeon's guide to stem cells, cancer stem cells, and brain tumor stem cells. Neurosurgery. 2009 Aug;65(2):237-49; discussion 249-50; quiz N6 Authors: Cheshier SH, Kalani MY, Lim M, Ailles L, Huhn SL, Weissman IL Stem cells and their potential applications have become the forefront of scientific, political, and ethical discourse. Whereas stem cells were long accepted as units of development and evolution, it is now becoming increasingly clear that they are also units of oncogenesis. Although the field of stem cell biology is expanding at an astounding rate, the data attained are not readily translatable for the physicians who may eventually deliver these tools to patients. Herein, we provide a brief review of stem cell and cancer stem cell biology and highlight the scientific and clinical implications of recent findings regarding the presence of cancer-forming stem cells in brain tumors. PMID: 19625901 [PubMed - indexed for MEDLINE] |
| Pluripotency rush! Molecular cues for pluripotency, genetic reprogramming of adult stem cells, and widely multipotent adult cells.
October 29, 2009 at 8:11 am
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| | Pluripotency rush! Molecular cues for pluripotency, genetic reprogramming of adult stem cells, and widely multipotent adult cells. Pharmacol Ther. 2009 Oct;124(1):23-30 Authors: Beltrami AP, Cesselli D, Beltrami CA In the last few years, pluripotent stem cells have been the objective of intense investigation efforts. These cells are of paramount therapeutic interest, since they could be utilized: as in vitro models of disease, for pharmaceutical screening purposes, and for the regeneration of damaged organs. Over the years, pluripotent cells have been cultured from teratomas, the inner cell mass, and primordial germ cells. Accumulating informations have partially decrypted the molecular machinery responsible for the maintenance of a very primitive state, permitting the reprogramming of differentiated cells. Although the debate is still open, an extreme excitement is arising from two strictly related possibilities: pluripotent cells could be obtained from adult tissues with minimal manipulations or very rare pluripotent cells could be identified in adult tissues. This intriguing option will trigger new researches aimed both at identifying the possible biological role of pluripotent adult stem cells and at exploiting their potential clinical use. The present review article will summarize current knowledge of the molecular cues for pluripotency but also discusses whether pluripotent stem cells could be obtained from adult tissues. PMID: 19545589 [PubMed - indexed for MEDLINE] |
| Exploring the link between microorganisms and oral cancer: a systematic review of the literature.
October 29, 2009 at 8:11 am
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| | Exploring the link between microorganisms and oral cancer: a systematic review of the literature. Head Neck. 2009 Sep;31(9):1228-39 Authors: Hooper SJ, Wilson MJ, Crean SJ The majority of cases of oral cancer have been related to tobacco use and heavy alcohol consumption. However, the incidence of oral cavity carcinoma appears to be increasing in many parts of the world in a manner that it is difficult to explain with traditional risk factors alone. Meanwhile, interest in the possible relationships between microorganisms and the different stages of cancer development has been rising and numerous mechanisms by which bacteria and yeast may initiate or promote carcinogenesis are currently under investigation. In particular, a persuasive body of evidence suggests a possible etiological role involving the metabolism and production of carcinogenic products, such as acetaldehyde. Other suggested mechanisms include the induction of chronic inflammation and direct interference with eukaryotic cell cycle and signaling pathways. This review aims to summarize the known associations between microbial infection and cancer and draw attention to how they may relate to oral carcinoma. PMID: 19475550 [PubMed - indexed for MEDLINE] |
| [Sciatic neuropathy after pelvic floor repair]
October 29, 2009 at 8:11 am
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| | [Sciatic neuropathy after pelvic floor repair] Urologe A. 2009 Aug;48(8):901-3 Authors: Shiozawa T, Reisenauer C After the surgical treatment of a recurrent enterocele and rectocele using a polypropylene implant, a patient developed a reversible paralysis. Haematoma was excluded. To search for the cause of the paralysis, polypropylene implants were inserted in four ethanol-preserved cadavers. Their dissection showed a safe distance at all points between the implant and the sciatic nerve. The patient's paralysis was most likely due to the lithotomy position, with an overstretching of the sciatic nerve during the intraoperative flexion of the hip joint. PMID: 19458931 [PubMed - indexed for MEDLINE] |
| Gemcitabine and capecitabine chemotherapy in Japanese patients with immunotherapy-resistant renal cell carcinoma.
October 29, 2009 at 8:11 am
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| | Gemcitabine and capecitabine chemotherapy in Japanese patients with immunotherapy-resistant renal cell carcinoma. Int J Urol. 2009 Jun;16(6):576-9 Authors: Soga N, Yamada Y, Nishikawa K, Hasegawa Y, Kise H, Arima K, Sugimura Y The objective of this study was to evaluate the efficacy and toxicity of combined gemcitabine and capecitabine (Gca) chemotherapy in patients with advanced renal cell cancer after immunotherapy failure. Nine patients were enrolled in this trial. Gemcitabine (1000 mg/m(2)) was injected on days 1 and 8, followed by oral administration of capecitabine (1660 mg/m(2)) on days 1-14. The response rate was 11%, with a partial response in one patient (11%), stable disease in five patients (56%) and disease progression in three patients (33%). Grade 3-4 neutropenia was observed in one patient (11%) and thrombocytopenia in two patients (22%). The quality of life (QOL) questionnaire scales showed no significant changes induced by chemotherapy. The median progression-free survival was 4 months with an overall 1-year survival rate of 78%. Gemcitabine and capecitabine chemotherapy can be safely administered as second-line therapy in renal cell cancer patients, maintaining QOL baseline parameters. PMID: 19456985 [PubMed - indexed for MEDLINE] |
| Bone marrow-derived mesenchymal stem cells promote angiogenic processes in a time- and dose-dependent manner in vitro.
October 29, 2009 at 8:11 am
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| | Bone marrow-derived mesenchymal stem cells promote angiogenic processes in a time- and dose-dependent manner in vitro. Tissue Eng Part A. 2009 Sep;15(9):2459-70 Authors: Duffy GP, Ahsan T, O'Brien T, Barry F, Nerem RM Bone marrow-derived mesenchymal stem cells (MSCs) have received much attention as a potential treatment for myocardial infarction because of their potential to integrate into the host myocardium and repair the injured heart. The mode of action of stem cell-mediated cardiac repair is still somewhat unclear, including the potential role of MSCs in neovascularization. The objective of this study was to determine the in vitro effect of MSCs on angiogenesis-related endothelial cell (EC) behavior, including migration, monolayer permeability, and vessel formation and stabilization. In a noncontact coculture system, we found that MSCs increase EC proliferation and migration, promoting early events of angiogenesis, while also decreasing EC monolayer permeability. Further, in a time- and dose-dependent manner, MSCs in direct coculture with ECs on Matrigel can increase the persistence of preexisting vessels by greater than threefold, with complex vessels remaining stable for more than 10 days. The results demonstrate that MSCs play an active role in the cellular processes involved in the formation, stabilization, and maturation of newly formed vessels. Further, these outcomes are not governed solely by either paracrine or direct contact effects and are both time and dose dependent. PMID: 19327020 [PubMed - indexed for MEDLINE] |
| The effect of perfluorocarbon-based artificial oxygen carriers on tissue-engineered trachea.
October 29, 2009 at 8:11 am
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| | The effect of perfluorocarbon-based artificial oxygen carriers on tissue-engineered trachea. Tissue Eng Part A. 2009 Sep;15(9):2471-80 Authors: Tan Q, El-Badry AM, Contaldo C, Steiner R, Hillinger S, Welti M, Hilbe M, Spahn DR, Jaussi R, Higuera G, van Blitterswijk CA, Luo Q, Weder W The biological effect of the perfluorocarbon-based artificial oxygen carrier (Oxygent) was investigated in tissue-engineered trachea (TET) construction. Media supplemented with and without 10% Oxygent were compared in all assessments. Partial tissue oxygen tension (PtO(2)) was measured with polarographic microprobes; epithelial metabolism was monitored by microdialysis inside the TET epithelium perfused with the medium underneath. Chondrocyte-DegraPol constructs were cultured for 1 month with the medium before glycosaminoglycan assessment and histology. Tissue reaction of TET epithelial scaffolds immersed with the medium was evaluated on the chick embryo chorioallantoic membrane. Oxygent perfusion medium increased the TET epithelial PtO(2) (51.2 +/- 0.3 mm Hg vs. 33.4 +/- 0.3 mm Hg at 200 microm thickness; 12.5 +/- 0.1 mm Hg vs. 3.1 +/- 0.1 mm Hg at 400 microm thickness, p < 0.01) and decreased the lactate concentration (0.63 +/- 0.08 vs. 0.80 +/- 0.06 mmol/L, p < 0.05), lactate/pyruvate (1.87 +/- 0.26 vs. 3.36 +/- 10.13, p < 0.05), and lactate/glucose ratios (0.10 +/- 0.00 vs. 0.29 +/- 0.14, p < 0.05). Chondrocyte-DegraPol in Oxygent group presented lower glycosaminoglycan value (0.03 +/- 0.00 vs. 0.13 +/- 0.00, p < 0.05); histology slides showed poor acid mucopolysaccharides formation. Orthogonal polarization spectral imaging showed no difference in functional capillary density between the scaffolds cultured on chorioallantoic membranes. The foreign body reaction was similar in both groups. We conclude that Oxygent increases TET epithelial PtO(2), improves epithelial metabolism, does not impair angiogenesis, and tends to slow cartilage tissue formation. PMID: 19292679 [PubMed - indexed for MEDLINE] |
| Construction of synthetic dermis and skin based on a self-assembled peptide hydrogel scaffold.
October 29, 2009 at 8:11 am
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| | Construction of synthetic dermis and skin based on a self-assembled peptide hydrogel scaffold. Tissue Eng Part A. 2009 Sep;15(9):2385-96 Authors: Kao B, Kadomatsu K, Hosaka Y Using biocompatible peptide hydrogel as a scaffold, we prepared three-dimensional synthetic skin that does not contain animal-derived materials or pathogens. The present study investigated preparation methods, proliferation, and functional expression of fibroblasts in the synthetic dermis and differentiation of keratinocytes in the epidermis. Synthetic dermis was prepared by mixing fibroblasts with peptide hydrogel, and synthetic skin was prepared by forming an epidermal layer using keratinocytes on the synthetic dermis. A fibroblast-rich foamy layer consisting of homogeneous peptide hydrogel subsequently formed in the synthetic dermis, with fibroblasts aggregating in clusters within the septum. The epidermis consisted of three to five keratinocyte layers. Immunohistochemical staining showed human type I collagen, indicating functional expression around fibroblasts in the synthetic dermis, keratinocyte differentiation in the epidermis, and expression of basement membrane proteins. The number of fibroblasts tended to increase until the second week and was maintained until the fourth week, but rapidly decreased in the fifth week. In the synthetic dermis medium, the human type I collagen concentration increased after the second week to the fifth week. These findings suggest that peptide hydrogel acts as a synthetic skin scaffold that offers a platform for the proliferation and functional expression of fibroblasts and keratinocytes. PMID: 19292667 [PubMed - indexed for MEDLINE] |
| Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation.
October 29, 2009 at 8:11 am
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| | Muscle differentiation and myotubes alignment is influenced by micropatterned surfaces and exogenous electrical stimulation. Tissue Eng Part A. 2009 Sep;15(9):2447-57 Authors: Flaibani M, Boldrin L, Cimetta E, Piccoli M, De Coppi P, Elvassore N An in vitro muscle-like structure with parallel-oriented contractile myotubes is needed as a model of muscle tissue regeneration. For this purpose, it is necessary to reproduce a controllable microscale environment mimicking the in vivo cues. In this work we focused on the application of topological and electrical stimuli on muscle precursor cell (MPC) culture to influence MPC orientation and induce myotube alignment. The two stimulations were tested both independently and together. A structural and topological template was achieved using micropatterned poly-(L-lactic acid) membranes. Electrical stimulation, consisting of square pulses of 70 mV/cm amplitude each 30 s, was applied to the MPC culture. The effect of different pulse durations on cultures was evaluated by galvanotaxis analysis. The highest cell displacement rate toward the cathode was observed for 3 ms pulse stimulation, which was then applied in combination with topological stimuli. Topological and electrical stimuli had an additive effect in enhancing differentiation of cultured MPC, shown by high Troponin I protein production and, in parallel, Myogenin and Desmin genes, down- and upregulation respectively. PMID: 19292666 [PubMed - indexed for MEDLINE] |
| Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells.
October 29, 2009 at 8:11 am
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| | Effect of fiber diameter and alignment of electrospun polyurethane meshes on mesenchymal progenitor cells. Tissue Eng Part A. 2009 Sep;15(9):2435-45 Authors: Bashur CA, Shaffer RD, Dahlgren LA, Guelcher SA, Goldstein AS Effective strategies to guide cell alignment and the deposition of an oriented extracellular matrix are critical for the development of anisotropic engineered tissues suitable for the repair of ligament defects. Electrospinning is a promising means to create meshes that can align adherent cells, but the effect of fiber mesh architecture on differentiation has not been examined closely. Therefore, the goal of this study was to determine the effect of fiber diameter and the degree of fiber alignment on mesenchymal progenitor cell morphology, proliferation, and ligament gene expression. Specifically, a poly(ester urethane)urea elastomer was electrospun onto rigid supports under conditions designed to independently vary the mean fiber diameter (from 0.28 to 2.3 microm) and the degree of fiber alignment. Bone marrow stromal cells--seeded onto supported meshes--adhered to and proliferated on all surfaces. Cells assumed a more spindle-shaped morphology with increasing fiber diameter and degree of fiber alignment, and oriented parallel to fibers on aligned meshes. Expression of the ligament markers collagen 1alpha1, decorin, and tenomodulin appeared to be sensitive to fiber diameter and greatest on the smallest fibers. Concurrently, expression of the transcription factor scleraxis appeared to decrease with increasing fiber alignment. These results suggest that the formation of a ligament-like tissue on electrospun scaffolds is enhanced when the scaffolds consist of aligned submicron fibers. PMID: 19292650 [PubMed - indexed for MEDLINE] |
| Zonal chondrocytes seeded in a layered agarose hydrogel create engineered cartilage with depth-dependent cellular and mechanical inhomogeneity.
October 29, 2009 at 8:11 am
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| | Zonal chondrocytes seeded in a layered agarose hydrogel create engineered cartilage with depth-dependent cellular and mechanical inhomogeneity. Tissue Eng Part A. 2009 Sep;15(9):2315-24 Authors: Ng KW, Ateshian GA, Hung CT We hypothesized that zonal populations of chondrocytes seeded into a bilayered scaffold with initially prescribed depth-varying, compressive material properties will lead to a biomimetic cartilage tissue construct with depth-dependent cellular and compressive mechanical inhomogeneity similar to that of the native tissue. Superficial zone chondrocytes (SZCs) and middle/deep zone chondrocytes (MDZCs) were isolated and encapsulated with 2% or 3% agarose to form single-layered constructs of 2% SZC, 3% SZC, 2% MDZC; bilayered constructs of 2% SZC/2% MDZC and 3% SZC/2% MDZC; and 2% mixed chondrocyte controls. For SZCs on day 42, increased glycosaminoglycan (GAG) and collagen was found with increased agarose concentration and when layered with MDZCs. Superficial zone protein increased with agarose concentration in bilayered constructs. For MDZCs, increased GAG content and regulation of cell proliferation was observed when layered with SZCs. Bilayered constructs possessed a depth-dependent compressive modulus qualitatively similar to that of native articular cartilage, whereas controls showed a U-shaped profile with stiffer peripheral edges and softer middle region. This study is the first to create an engineered cartilage tissue with depth-varying cellular as well as mechanical inhomogeneity. Future studies will determine if replicating inhomogeneity is advantageous in clinical applications of tissue engineered cartilage. PMID: 19231936 [PubMed - indexed for MEDLINE] |
| Controlled release of matrix metalloproteinase 1 with or without skeletal myoblasts transplantation improves cardiac function of rat hearts with chronic myocardial infarction.
October 29, 2009 at 8:11 am
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| | Controlled release of matrix metalloproteinase 1 with or without skeletal myoblasts transplantation improves cardiac function of rat hearts with chronic myocardial infarction. Tissue Eng Part A. 2009 Sep;15(9):2699-706 Authors: Lin X, Tammbara K, Fu M, Yamamoto M, Premaratne GU, Sakakibara Y, Marui A, Ikeda T, Komeda M, Tabata Y Skeletal myoblast transplantation has been applied clinically for severe ischemic cardiomyopathy. Matrix metalloproteinase 1 (MMP-1) reduces fibrosis and prevents the progress of heart failure. We hypothesized that MMP-1 administration to the infarct area enhances the efficacy of skeletal myoblast transplantation. The controlled release of MMP-1 improved cardiac functions of rats with chronic myocardiac infarction with or without transplantation of skeletal myoblasts. Improvement in cardiac function and small fibrotic area inside the infarcted area were observed compared with those of myoblast transplantation. In conclusion, controlled release of MMP-1 was effective in cardioprotection in postmyocardial infarction although the combination with cell transplantation showed the similar effect. PMID: 19216640 [PubMed - indexed for MEDLINE] |
| Development of decellularized human umbilical arteries as small-diameter vascular grafts.
October 29, 2009 at 8:11 am
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| | Development of decellularized human umbilical arteries as small-diameter vascular grafts. Tissue Eng Part A. 2009 Sep;15(9):2665-76 Authors: Gui L, Muto A, Chan SA, Breuer CK, Niklason LE OBJECTIVE: Developing a tissue-engineered small-diameter (<6mm) vascular graft for reconstructive surgery has remained a challenge for the past several decades. This study was conducted to develop a decellularized umbilical artery and to evaluate its composition, endothelial cell compatibility, mechanical properties, and in vivo stability for potential use as a small-diameter vascular graft. METHODS AND RESULTS: Human umbilical arteries were isolated and decellularized by incubation in CHAPS and sodium dodecyl sulfate buffers followed by incubation in endothelial growth media-2. Decellularized umbilical arteries were completely devoid of cellular and nuclear material while retaining the integrity of extracellular collagenous matrix. The mechanical strength of the decellularized umbilical artery as assessed by its burst pressure in vitro showed no significant change from its native form. Decellularized umbilical arteries supported endothelial adherence as indicated by the re-endotheliazation with a monolayer of human umbilical vein endothelial cells. Furthermore, decellularized vessels that were implanted into nude rats as abdominal aorta interposition grafts remained mechanically intact and patent for up to 8 weeks. CONCLUSION: Decellularized human umbilical arteries preserved the extracellular matrix, supported endothelialization, and retained function in vivo for up to 8 weeks. These properties suggest the potential use of decellularized umbilical arteries as small-diameter vascular grafts. PMID: 19207043 [PubMed - indexed for MEDLINE] |
| Toward regenerating a human thumb in situ.
October 29, 2009 at 8:11 am
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| | Toward regenerating a human thumb in situ. Tissue Eng Part A. 2009 Sep;15(9):2605-15 Authors: Weinand C, Gupta R, Weinberg E, Madisch I, Neville CM, Jupiter JB, Vacanti JP Regenerative technology promises to alleviate the problem of limited donor supply for bone or organ transplants. Most expensive and time consuming is cell expansion in laboratories. We propose a method of magnetically enriched osteoprogenitor stem cells, dispersed in self-assembling hydrogels and applied onto new ultra-high resolution, jet-based, three-dimensional printing of living human bone in a single-step for in situ bone regeneration. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were enriched with CD 117+ cells, dispersed in different collagen I and RAD 16I hydrogel mixes, and applied onto three-dimensional printed btricalcium phosphate=poly(lactic-co-glycolic acid) scaffolds, printed from ultra-high-resolution volumetric CT images of a human thumb. Constructs were directly implanted subcutaneously into nude mice for 6 weeks. In vivo radiographic volumetric CT scanning and histological evaluations were performed at 1, 2, 4, and 6 weeks, and expression of bone-specific genes and biomechanical compression testing at 6 weeks endpoint. Time-dependant accumulation of bone-like extracellular matrix was most evident in CD 117+ hBMSCs using collagen I=RAD 16I hydrogel mix. This was shown histologically by Toluidine blue, von Kossa, and alkaline phosphatase staining, paralleled by increased radiological densities within implants approximating that of human bone, and confirmed by high expression of bone-specific osteonectin and biomechanical stiffness at 6 weeks. Human origin of newly formed tissue was established by expression of human GAPDH using RT-PCR. Statistical analysis confirmed high correlations between biomechanical stiffness, radiological densities, and bone markers. Bone tissue can be successfully regenerated in vivo using a single-step procedure with constructs composed of RAD 16I=collagen I hydrogel, CD 117+-enriched hBMSCs, and porous b-tricalcium phosphate=poly(lactic-co-glycolic acid) scaffolds. PMID: 19199577 [PubMed - indexed for MEDLINE] |
| Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules.
October 29, 2009 at 8:11 am
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| | Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules. Biol Reprod. 2007 Feb;76(2):211-7 Authors: Kita K, Watanabe T, Ohsaka K, Hayashi H, Kubota Y, Nagashima Y, Aoki I, Taniguchi H, Noce T, Inoue K, Miki H, Ogonuki N, Tanaka H, Ogura A, Ogawa T Testicular germ cell transplantation into the seminiferous tubules is at present the only way to induce spermatogenesis from a given source of spermatogonial stem cells. Here we show an alternative method that harnesses the self-organizing ability of testicular somatic cells. The testicular cells of embryonic or neonatal mice or rats and of newborn pigs were dissociated into single cells. Each of them reorganized into a tubular structure following implantation into the subcutis of immunodeficient mice. When mouse germline stem (GS) cells derived from spermatogonial stem cells and expanded in culture were intermingled with testicular cells of rodents, they were integrated in the reconstituted tubules and differentiated beyond meiosis into spermatids. Normal offspring were produced by the microinjection of those spermatids into oocytes. This method could be applicable to various mammalian species and useful for producing functional gametes from GS cells in a xenoectopic environment. PMID: 17065598 [PubMed - indexed for MEDLINE] | | | 
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