| X-linked Foxp3 (Scurfy) mutation dominantly inhibits submandibular gland development and inflammation respectively through adaptive and innate immune mechanisms.
September 19, 2009 at 6:03 pm
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| | X-linked Foxp3 (Scurfy) mutation dominantly inhibits submandibular gland development and inflammation respectively through adaptive and innate immune mechanisms. J Immunol. 2009 Sep 1;183(5):3212-8 Authors: Sharma R, Deshmukh US, Zheng L, Fu SM, Ju ST Scurfy (Foxp3(Sf)/Y), Il2(-/-), and Il2ralpha(-/-) mice are deficient in CD4(+)Foxp3(+) regulatory T cells (Treg), but only the latter two develop inflammation in the submandibular gland (SMG), a critical target of Sjögren's syndrome. In this study, we investigated the reason that SMG of Scurfy (Sf), Sf.Il2(-/-), Sf.Il2ralpha(-/-), and the long-lived Sf.Fas(lpr/lpr) mice remained free of inflammation, even though their lymph node cells induced SMG inflammation in Rag1(-/-) recipients. A strong correlation was observed between the development of the granular convoluted tubules (GCT) of the SMG in these mice and SMG resistance to inflammation. Moreover, GCT development in Sf.Rag1(-/-) mice was not impeded, indicating a role of adaptive immunity. In the Sf.Fas(lpr/lpr) mice, this block was linked to atrophy and inflammation in the accessory reproductive organs. Testosterone treatment restored GCT expression, but did not induce SMG inflammation, indicating GCT is not required for inflammation and additional mechanisms were controlling SMG inflammation. Conversely, oral application of LPS induced SMG inflammation, but not GCT expression. LPS treatment induced up-regulation of several chemokines in SMG with little effect on the chemokine receptors on CD4(+) T cells in Sf mice. Our study demonstrates that Sf mutation affects SMG development through adaptive immunity against accessory reproductive organs, and the manifestation of SMG inflammation in Sf mice is critically controlled through innate immunity. PMID: 19648271 [PubMed - indexed for MEDLINE] |
| Embryological development of the human insula and its implications for the spread and resection of insular gliomas.
September 19, 2009 at 6:03 pm
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| | Embryological development of the human insula and its implications for the spread and resection of insular gliomas. Neurosurg Focus. 2009 Aug;27(2):E2 Authors: Kalani MY, Kalani MA, Gwinn R, Keogh B, Tse VC The human insular cortex, or the lobus insularis, is considered the developmentally most primitive lobe of the telencephalon. Covered by an overlying cortical lid, the insula has functions that are distinct from yet related to those of the adjacent temporal lobe and deep limbic structures. In the first part of this paper the authors outline the development of the human insula, including the cellular heterogeneity comprising the various parts of the insular lobe. Using the understanding gained from the development of the insula they then address implications of insular development for cortical development and connection as well as for tumorigenesis and tumor spread from the insula to other cortical structures, most notably the temporal lobe. An understanding of cortico-insular development and interconnection allows for both a better understanding of insular pathology and also facilitates planning of resection of cortico-insular gliomas to avoid damage to eloquent structures. PMID: 19645558 [PubMed - indexed for MEDLINE] |
| Induction of oligodendrogenesis in glioblastoma-initiating cells by IFN-mediated activation of STAT3 signaling.
September 19, 2009 at 6:03 pm
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| | Induction of oligodendrogenesis in glioblastoma-initiating cells by IFN-mediated activation of STAT3 signaling. Cancer Lett. 2009 Oct 18;284(1):71-9 Authors: Yuki K, Natsume A, Yokoyama H, Kondo Y, Ohno M, Kato T, Chansakul P, Ito M, Kim SU, Wakabayashi T The response of cancer patients to interferon (IFN) treatment is long-lasting, indicating that IFN may act on small cancer stem cell populations. Glioma-initiating cells (GICs) can self-renew and induce the formation of heterogeneously differentiated tumor cells and are resistant to chemotherapeutic agents like temozolomide. In this study, we showed that via STAT3 signaling, IFN-beta suppressed the proliferation, self-renewal, and tumorigenesis of GICs, induced their terminal differentiation to mature oligodendroglia-like cells, and exhibited synergistic cytotoxicity with temozolomide. Therefore, IFN may be a potential therapeutic agent for inducing the terminal differentiation of GICs. PMID: 19457609 [PubMed - indexed for MEDLINE] |
| Effective inhibition of human cytomegalovirus gene expression by DNA-based external guide sequences.
September 19, 2009 at 6:03 pm
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| | Effective inhibition of human cytomegalovirus gene expression by DNA-based external guide sequences. Acta Biochim Biophys Sin (Shanghai). 2009 May;41(5):389-98 Authors: Zeng Z, Li H, Li Y, Cui Y, Zhou Q, Zou Y, Yang G, Zhou T To investigate whether a 12 nucleotide DNA-based miniEGSs can silence the expression of human cytomegalovirus (HCMV) UL49 gene efficiently, A HeLa cell line stably expressing UL49 gene was constructed and the putative miniEGSs (UL49-miniEGSs) were assayed in the stable cell line. Quantitative RT-PCR and western blot results showed a reduction of 67% in UL49 expression level in HeLa cells that were transfected with UL49-miniEGSs. It was significantly different from that of mock and control miniEGSs (TK-miniEGSs) which were 1% and 7%, respectively. To further confirm the gene silence directed by UL49-miniEGSs with human RNase P, a mutant of UL49-miniEGSs was constructed and a modified 5'RACE was carried out. Data showed that the inhibition of UL49 gene expression directed by UL49-miniEGSs was RNase P-dependent and the cleavage of UL49 mRNA by RNase P was site specific. As a result, the length of DNA-based miniEGSs that could silence gene expression efficiently was only 12 nt. That is significantly less than any other oligonucleotide-based method of gene inactivation known so far. MiniEGSs may represent novel gene-targeting agents for the inhibition of viral genes and other human disease related gene expression. PMID: 19430703 [PubMed - indexed for MEDLINE] |
| Launching intravenous bone marrow cell trials for acute stroke.
September 19, 2009 at 6:03 pm
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| | Launching intravenous bone marrow cell trials for acute stroke. Regen Med. 2009 Sep;4(5):639-41 Authors: Savitz SI, Misra V PMID: 19761387 [PubMed - in process] |
| Bioaesthetics and regenerative medicine.
September 19, 2009 at 6:03 pm
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| | Bioaesthetics and regenerative medicine. Regen Med. 2009 Sep;4(5):635-7 Authors: Mason C, Manzotti E PMID: 19761386 [PubMed - in process] |
| Parthenogenesis and somatic cell nuclear transfer in sheep oocytes using Polscope.
September 19, 2009 at 6:03 pm
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| | Parthenogenesis and somatic cell nuclear transfer in sheep oocytes using Polscope. Indian J Exp Biol. 2009 Jul;47(7):550-8 Authors: Nandedkar P, Chohan P, Patwardhan A, Gaikwad S, Bhartiya D Parthenogenesis and Somatic cell nuclear transfer (SCNT) techniques, offer a unique approach to manipulate the genetic composition of derived human embryonic stem cells - an essential step if the full opportunities for disease modeling, drug discovery or individualized stem cell therapy are to be realized. The present study describes the use of sheep oocytes to acquire expertise and establish methods to reconstruct embryos for obtaining blastocysts before venturing into human SCNT where the oocytes are a very precious starting material. Maturation of sheep eggs in vitro for 20-24 hr resulted in 65% metaphase II (MII) eggs which were either parthenogenetically activated using calcium ionomycin or ethanol or subjected to SCNT using cumulus cell as somatic cell. Sixteen blastocysts were produced by parthenogenetic activation of 350 eggs whereas reconstructed embryos, after SCNT carried out in 139 eggs, progressed only up to morula stage. The procedure of parthenogenesis and SCNT will be useful to generate autologous ES cells using human eggs. PMID: 19761038 [PubMed - in process] |
| Structural and morphologic evaluation of a novel detergent-enzymatic tissue-engineered tracheal tubular matrix.
September 19, 2009 at 6:03 pm
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| | Structural and morphologic evaluation of a novel detergent-enzymatic tissue-engineered tracheal tubular matrix. J Thorac Cardiovasc Surg. 2009 Sep;138(3):586-93; discussion 592-3 Authors: Jungebluth P, Go T, Asnaghi A, Bellini S, Martorell J, Calore C, Urbani L, Ostertag H, Mantero S, Conconi MT, Macchiarini P OBJECTIVE: We sought to bioengineer a nonimmunogenic tracheal tubular matrix of 6 cm in length and test its structural, functional, and immunologic properties in vitro and in vivo. METHODS: Twelve-centimeter tracheal segments were harvested from Yorkshire boars. Half of each segment was subjected to a detergent-enzymatic method (containing sodium deoxycholate/DNase lavations) of decellularization for as many cycles as needed, and the other half was stored in phosphate-buffered saline at 4 degrees C as a control. Bioengineered and control tracheas were then implanted in major histocompatibility complex-unmatched pigs (allograft) or mice (xenograft) heterotopically for 30 days. Structural and functional analysis and immunostaining were performed after each detergent-enzymatic method cycle and transplantation. RESULTS: Compared with control tracheas, bioengineered matrices displayed no major histocompatibility complex class I and II antigens after 17 detergent-enzymatic method cycles, without significant (P > .05) differences in their strain ability (rupture force, 56.1 +/- 3.3 vs 55.5 +/- 2.4 N; tissue deformation at 203% +/- 13% vs 200% +/- 8% or 12.2 +/- 0.8 vs 12 +/- 0.5 cm; and applied maximum force, 173.4 +/- 3.2 vs 171.5 +/- 4.6 N). Thirty days after implantation, significantly (P < .01) smaller inflammatory reactions (392 vs 15 macrophages/mm(2) and 874 vs 167 T lymphocytes/mm(2)) and P-selectin expressions (1/6 vs 6/6) were observed in both the xenograft and allograft models with bioengineered matrices compared with those seen with control tracheas. There was no development of anti-pig leukocyte antigen antibodies or increase in both IgM and IgG content in mice implanted with bioengineered tracheas. CONCLUSIONS: Bioengineered tracheal matrices displayed similar structural and mechanical characteristics to native tracheas and excite no immune response to 30 days when implanted as allografts or xenografts. This method holds great promise for the future of tissue-engineered airway replacement. PMID: 19698839 [PubMed - indexed for MEDLINE] |
| Research highlights.
September 19, 2009 at 6:03 pm
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| | Research highlights. Regen Med. 2009 Sep;4(5):663-6 Authors: Gyöngyösi M PMID: 19761391 [PubMed - in process] |
| Interview: Discussions on the development of human embryonic stem cell-based therapies.
September 19, 2009 at 6:03 pm
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| | Interview: Discussions on the development of human embryonic stem cell-based therapies. Regen Med. 2009 Sep;4(5):659-61 Authors: Lebkowski JS Dr Jane Lebkowski joined Geron Corporation in 1998 and is currently Senior Vice President and Chief Scientific Officer of the Regenerative Medicine Division. Dr Lebkowski heads Geron's human embryonic stem cell program, and is responsible for all research, preclinical development, product development, manufacturing and clinical development activities. Prior to Geron, Dr Lebkowski was Vice President of Research and Development at Applied Immune Sciences. Following the acquisition of Applied Immune Sciences by Rhone Poulenc Rorer (RPR, currently Sanofi-Aventis), Dr Lebkowski remained at RPR as Vice President of Discovery Research. During Dr Lebkowski's tenure at RPR, she coordinated preclinical investigations of gene-therapy approaches for treatment of cancer, cardiovascular disease and nervous system disorders, and directed vector formulations and delivery development. Dr Lebkowski received her PhD in Biochemistry from Princeton University in 1982, and completed a postdoctoral fellowship at the Department of Genetics, Stanford University (CA, USA) in 1986. Dr Lebkowski has published over 70 peer-reviewed papers and has 12 issued US patents. Dr Lebkowski serves as the co-chair of the Industrial Committee of the International Society for Stem Cell Research and serves on the editorial boards of several scientific publications. PMID: 19761390 [PubMed - in process] |
| Industry Update: Latest developments in stem cell research and regenerative medicine.
September 19, 2009 at 6:03 pm
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| | Industry Update: Latest developments in stem cell research and regenerative medicine. Regen Med. 2009 Sep;4(5):647-57 Authors: Ilic D PMID: 19761389 [PubMed - in process] |
| News & views in ... Regenerative medicine.
September 19, 2009 at 6:03 pm
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| | News & views in ... Regenerative medicine. Regen Med. 2009 Sep;4(5):643-5 Authors: PMID: 19761388 [PubMed - in process] |
| Pulp and dentin tissue engineering and regeneration: current progress.
September 19, 2009 at 6:03 pm
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| | Pulp and dentin tissue engineering and regeneration: current progress. Regen Med. 2009 Sep;4(5):697-707 Authors: Huang GT Dental pulp tissue is vulnerable to infection. Entire pulp amputation followed by pulp-space disinfection and filling with an artificial rubber-like material is employed to treat the infection - commonly known as root-canal therapy. Regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. However, with the advent of the concept of modern tissue engineering and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the early attempts to regenerate pulp tissue and the current endeavor of pulp and dentin tissue engineering, and regeneration. The prospective outcome of the current advancement in this line of research will be discussed. PMID: 19761395 [PubMed - in process] |
| Ficoll-Paque versus Lymphoprep: a comparative study of two density gradient media for therapeutic bone marrow mononuclear cell preparations.
September 19, 2009 at 6:03 pm
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| | Ficoll-Paque versus Lymphoprep: a comparative study of two density gradient media for therapeutic bone marrow mononuclear cell preparations. Regen Med. 2009 Sep;4(5):689-96 Authors: Yeo C, Saunders N, Locca D, Flett A, Preston M, Brookman P, Davy B, Mathur A, Agrawal S Aims: Contradictory outcomes from recent clinical trials investigating the transplantation of autologous bone marrow mononuclear cell (BM-MNC) fraction containing stem/progenitor cells to damaged myocardium, following acute myocardial infarction, may be, in part, due to the different cell isolation protocols used. We compared total BM-MNC numbers and its cellular subsets obtained following isolation using Ficoll-Paque and Lymphoprep - two different density gradient media used in the clinical trials. Materials & methods: Bone marrow samples were taken from patients entered into the REGENERATE-IHD clinical trial after 5 days of subcutaneous granulocyte colony-stimulating factor injections. Each sample was divided equally for BM-MNC isolation using Ficoll-Paque and Lymphoprep, keeping all other procedural steps constant. Isolated fractions were characterized for hematopoietic stem cells, endothelial progenitor cells, T lymphocytes, B lymphocytes and NK cells using cell surface markers CD34(+), CD133(+)VEGFR2(+), CD45(+)CD3(+), CD45(+)CD19(+) and CD45(+)CD16(+)CD56(+), respectively. There were no significant differences in the absolute numbers and percentage cell recovery of various mononuclear cell types recovered following separation using either density gradient media. Cell viability and the proportion of various cell phenotypes investigated were similar between the two media. They were also equally efficient in excluding unwanted red blood cells, granulocytes and platelets from the final cell products. Conclusion: We demonstrated that the composition and quantity of cell types found within therapeutic BM-MNC preparations for use in clinical trials of cardiac stem cell transplantation are not influenced by the type of density gradient media used when comparing Ficoll-Paque and Lymphoprep. PMID: 19761394 [PubMed - in process] |
| Conjunctival epithelial cells maintain stem cell properties after long-term culture and cryopreservation.
September 19, 2009 at 6:03 pm
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| | Conjunctival epithelial cells maintain stem cell properties after long-term culture and cryopreservation. Regen Med. 2009 Sep;4(5):677-87 Authors: Schrader S, Notara M, Beaconsfield M, Tuft S, Geerling G, Daniels J Aim: Transplantation of tissue-engineered conjunctival epithelial cell sheets has proven to be a promising technique for conjunctival reconstruction. The ability to cryopreserve conjunctival epithelial cells and maintain their stem cell population would improve their availability for clinical use. The aim of this study was to evaluate whether cryopreservation and long-term in vitro culture has an effect on the proliferative capacity and the progenitor-like cell characteristics of conjunctival epithelial cells. Method: Human conjunctival cells from bulbar biopsies were isolated and expanded on a growth arrested 3T3 feeder layer. The cells were evaluated for cytokeratin (CK4/CK19) expression by immunostaining. An aliquot with half of the cells from the initial culture was frozen in liquid nitrogen and stored for 14 days and, in addition, donor cells were cryopreserved for more than 6 months (202.7 +/- 13.0 days). Both cryopreserved and noncryopreserved cells were serially cultivated over four passages. For each passage the colony-forming efficiency and the cell population doubling rates were evaluated, and expression of putative progenitor cell markers, p63alpha and ABCG2, was assessed by immunostaining and reverse transcription PCR. Results: Both noncryopreserved and cryopreserved cells demonstrated a high colony-forming capacity that decreased with passage. Cells from both groups underwent approximately 20 cell population doublings before senescence. Immunoreactivity to p63alpha and ABCG2 was found in both groups until passage 4 and their presence was also confirmed by reverse transcription PCR. No difference in cell viability, colony-forming efficiency and immunoreactivity to p63alpha and ABCG2 was observed between cells cryopreserved for 14 days, and more than 6 months (202.7 +/- 13.0 days). Conclusion: Conjunctival epithelial cells with progenitor cell-like characteristics can be efficiently cryopreserved and can subsequently maintain their function in vitro over several culture passages. The option to cryopreserve conjunctival cells prior to in vitro expansion would be an advantage when cells have to be cultivated for clinical transplantation. PMID: 19761393 [PubMed - in process] |
| Hair follicle neogenesis induced by cultured human scalp dermal papilla cells.
September 19, 2009 at 6:03 pm
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| | Hair follicle neogenesis induced by cultured human scalp dermal papilla cells. Regen Med. 2009 Sep;4(5):667-76 Authors: Qiao J, Zawadzka A, Philips E, Turetsky A, Batchelor S, Peacock J, Durrant S, Garlick D, Kemp P, Teumer J Aim: To develop a method by which human hair follicle dermal papilla (DP) cells can be expanded in vitro while preserving their hair-inductive potential for use in follicular cell implantation, a cellular therapy for the treatment of hair loss. Materials & methods: DP cells were isolated from scalp hair follicles in biopsies from human donors. DP cell cultures were established under conditions that preserved their hair-inductive potential and allowed for significant expansion. The hair-inductive potential of cells cultured for approximately 36 doublings was tested in an in vivo flap-graft model. In some experiments, DiI was used to label cells prior to grafting. Results: Under the culture conditions developed, cultures established from numerous donors reproducibly resulted in an expansion that averaged approximately five population doublings per passage. Furthermore, the cells consistently induced hair formation in an in vivo graft assay. Grafted DP cells appeared in DP structures of newly formed hairs, as well as in the dermal sheath and in the dermis surrounding follicles. Induced hair follicles persisted and regrew after being plucked 11 months after grafting. Conclusion: A process for the propagation of human DP cells has been developed that provides significant expansion of cells and maintenance of their hair-inductive capability, overcoming a major technical obstacle in the development of follicular cell implantation as a treatment for hair loss. PMID: 19761392 [PubMed - in process] |
| Intracoronary blood- or bone marrow-derived cell transplantation in patients with ischemic heart disease.
September 19, 2009 at 6:03 pm
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| | Intracoronary blood- or bone marrow-derived cell transplantation in patients with ischemic heart disease. Regen Med. 2009 Sep;4(5):709-19 Authors: Reffelmann T, Kloner RA Soon after the first experimental scientific investigations of cell transplantation in various animal models of myocardial infarction and left ventricular dysfunction, a growing number of clinical trials evaluated the effects of intracoronary injection of peripheral blood- or bone marrow-derived cells in patients with myocardial infarction or chronic ischemic heart disease. In most of these trials, changes in parameters of left ventricular remodeling over time, such as left ventricular volumes, ejection fraction or infarct size, were used as trial end points, whereas information on mortality and morbidity after cell transplantation is sparse. Several meta-analyses, each including various sets of studies, estimated that intracoronary cell therapy was associated with small reductions in left ventricular end-systolic volumes and a moderate increase in left ventricular ejection fraction of 2.9-6.1% over time compared with control patients. As most of the clinical trials included a limited number of patients, results vary substantially between different studies. When evaluating whether effects of intracoronary cell transplantation on parameters of left ventricular remodeling may be transferable to meaningful consequences in terms of clinical outcome, the following aspects appear to be imperative. Robust data on mortality and clinical events based on a sufficient number of patients are required. Furthermore, effects of cell therapy must be compared with established therapeutic concepts for the treatment of myocardial infarction, such as reperfusion therapy or pharmacological interventions aiming at favorably influencing the remodeling process. Moreover, the potential effects of cell therapy must be evaluated as treatment options additive to established therapeutic strategies. PMID: 19761396 [PubMed - in process] |
| Engineering microenvironments for embryonic stem cell differentiation to cardiomyocytes.
September 19, 2009 at 6:03 pm
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| | Engineering microenvironments for embryonic stem cell differentiation to cardiomyocytes. Regen Med. 2009 Sep;4(5):721-32 Authors: Horton RE, Millman JR, Colton CK, Auguste DT Embryonic stem cells and induced pluripotent stem cells have the potential to be a renewable source of cardiomyocytes for use in myocardial cell replacement strategies. Although progress has been made towards differentiating stem cells to specific cell lineages, the efficiency is often poor and the number of cells generated is not suitable for therapeutic usage. Recent studies demonstrated that controlling the stem cell microenvironment can influence differentiation. Components of the extracellular matrix are important physiological regulators and can provide mechanical cues, direct differentiation and improve cell engraftment into damaged tissue. Bioreactors are used to control the microenvironment and produce large numbers of desired cells. This article describes recent methods to achieve cardiomyocyte differentiation by engineering the stem cell microenvironment. Successful translation of stem cell research to therapeutic applications will need to address large-scale cardiomyocyte differentiation and purification, assessment of cardiac function and synchronization, and safety concerns. PMID: 19761397 [PubMed - in process] |
| Microencapsulated stem cells for tissue repairing: implications in cell-based myocardial therapy.
September 19, 2009 at 6:03 pm
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| | Microencapsulated stem cells for tissue repairing: implications in cell-based myocardial therapy. Regen Med. 2009 Sep;4(5):733-45 Authors: Paul A, Ge Y, Prakash S, Shum-Tim D Stem cells have the unique properties of self-renewal, pluripotency and a high proliferative capability, which contributes to a large biomass potential. Hence, these cells act as a useful source for acquiring renewable adult cell lines. This, in turn, acts as a potent therapeutic tool to treat various diseases related to the heart, liver and kidney, as well as neurodegenerative diseases such as Parkinson's and Alzheimer's disease. However, a major problem that must be overcome before it can be effectively implemented into the clinical setting is a suitable delivery system that can retain an optimal quantity of the cells at the targeted site for a maximal clinical benefit; a system that will give a mechanical as well as an immune protection to the foreign cells, while at the same time enhancing the yields of differentiated cells, maintaining cell microenvironments and sustaining the differentiated cell functions. To address this issue we opted for a novel delivery system, termed the 'artificial cells', which are semipermeable microcapsules with strong and thin multilayer membrane components with specific mass transport properties. Here, we briefly introduce the concept of artificial cells for encapsulation of stem cells and investigate the application of microencapsulation technology as an ideal tool for all stem transplantations and relate their role to the emerging field of cellular cardiomyoplasty. PMID: 19761398 [PubMed - in process] |
| Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials.
September 19, 2009 at 6:03 pm
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| | Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials. Regen Med. 2009 Sep;4(5):747-58 Authors: Traphagen S, Yelick PC The ability to engineer whole organs as replacements for allografts and xenografts is an ongoing pursuit in regenerative medicine. While challenges remain, including systemic tissue integration with angiogenesis, lymphatiogenesis and neurogenesis, ongoing efforts are working to develop novel technologies to produce implantable engineered scaffolds and potentially engineered whole organs. Natural extracellular matrix materials, commonly utilized in vitro, are now being used as effective, natural, acellular allografts, and are being integrated into nanoscale scaffolds and matrices with programmable responsiveness. Based on the significant use of natural scaffolds for tissue regeneration and bioengineering strategies, this review focuses on recent and ongoing efforts to engineer whole organs, such as the tooth, featuring natural extracellular matrix molecules. PMID: 19761399 [PubMed - in process] |
| Induced pluripotent stem cells in regenerative medicine: an argument for continued research on human embryonic stem cells.
September 19, 2009 at 6:03 pm
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| | Induced pluripotent stem cells in regenerative medicine: an argument for continued research on human embryonic stem cells. Regen Med. 2009 Sep;4(5):759-69 Authors: Lee H, Park J, Forget BG, Gaines P Human embryonic stem cells (ESCs) can be induced to differentiate into a wide range of tissues that soon could be used for therapeutic applications in regenerative medicine. Despite their developmental potential, sources used to generate human ESC lines raise serious ethical concerns, which recently prompted efforts to reprogram somatic cells back to a pluripotent state. These efforts resulted in the generation of induced pluripotent stem (iPS) cells that are functionally similar to ESCs. However, the genetic manipulations required to generate iPS cells may complicate their growth and developmental characteristics, which poses serious problems in predicting how they will behave when used for tissue-regenerative purposes. In this article we summarize the recently developed methodologies used to generate iPS cells, including those that minimize their genetic manipulation, and discuss several important complicating features of iPS cells that may compromise their future use for therapies in regenerative medicine. PMID: 19761400 [PubMed - in process] |
| Acknowledgements.
September 19, 2009 at 6:03 pm
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| | Acknowledgements. Regen Med. 2009 Sep;4(5):781 Authors: PMID: 19761401 [PubMed - in process] |
| Transplanted Bone Morphogenetic Protein/Poly(lactic-co-glycolic Acid) Delayed-release Microcysts Combined with Rat Micromorselized Bone and Collagen for Bone Tissue Engineering.
September 19, 2009 at 6:03 pm
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| | Transplanted Bone Morphogenetic Protein/Poly(lactic-co-glycolic Acid) Delayed-release Microcysts Combined with Rat Micromorselized Bone and Collagen for Bone Tissue Engineering. J Int Med Res. 2009 Jul-Aug;37(4):1075-87 Authors: Ji Y, Xu GP, Yan JL, Pan SH This study was designed to optimize the preparation of delayed-release microcysts containing bone morphogenetic protein 2 (BMP-2) combined with poly(lactic-co-glycolic acid) (PLGA) and to investigate their osteogenic properties when combined with rat autologous micromorselized bone and collagen. Rat autologous micromorselized bone, collagen and BMP-2/PLGA delayed-release microcysts were implanted in various combinations into the rat gluteus maximus muscle sack model. The following post-operative measurements were made: general observations of the implant site, histological observations, osteogenesis measurements and alkaline phosphatase activity. Autologous micromorselized bone combined with collagen and BMP-2/PLGA delayed-release microcysts demonstrated significantly superior osteogenic properties than any of the other combinations of these three components. These findings suggest that micromorselized bone combined with collagen and BMP-2/PLGA delayed-release microcysts could reduce the quantity of BMP-2 and autologous bone required for these procedures, making their use feasible in human bone restoration. PMID: 19761690 [PubMed - in process] |
| Size dependent release of fluorescent macromolecules and nanoparticles from radically cross-linked hydrogels.
September 19, 2009 at 6:03 pm
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| | Size dependent release of fluorescent macromolecules and nanoparticles from radically cross-linked hydrogels. Eur J Pharm Biopharm. 2009 Sep 14; Authors: Henke M, Brandl F, Goepferich AM, Tessmar JK Hydrogels play an important role for drug delivery and tissue engineering applications due to their excellent biocompatibility and their variable mechanical and physical properties, which allow their optimization for many different aspects of the intended use. In this study we examined the suitability of poly(ethylene glycol) [PEG] based hydrogels as release systems for nanometer-sized drugs or drug carriers, like nanoparticles, using the radically cross-linkable oligo(poly(ethylene glycol)fumarate) [OPF] together with two cross-linking agents. Different fluorescent nanoparticulate probes with respect to size and physical structure were incorporated in the cross-linked hydrogels and the obtained release profiles were correlated with the physical properties and the chemical structure of the gels, indicating a strong dependence of the release on the chosen PEG prepolymers. The prepared hydrogels were characterized by oscillatory rheometry and swelling experiments. Release experiments as well as diffusion measurements using fluorescence recovery after photobleaching showed the great potential of this type of hydrogels for the preparation of adjustable release systems by altering the molecular weights of the used PEG molecules. PMID: 19761843 [PubMed - as supplied by publisher] |
| Systematic Evaluation of a Tissue-Engineered Bone for Maxillary Sinus Augmentation in Large Animal Canine Model.
September 19, 2009 at 6:03 pm
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| | Systematic Evaluation of a Tissue-Engineered Bone for Maxillary Sinus Augmentation in Large Animal Canine Model. Bone. 2009 Sep 14; Authors: Wang S, Zhang Z, Xia L, Zhao J, Sun X, Zhang X, Ye D, Uludağ H, Jiang X The objective of this study is to systematically evaluate the effects of a tissue-engineered bone complex for maxillary sinus augmentation in a canine model. Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally and randomly repaired with the following 3 groups of grafts: Group A consisted of tissue-engineered osteoblasts/beta-TCP complex (n = 4); Group B consisted of beta-TCP alone (n = 4); Group C consisted of autogenous bone obtained from iliac crest as a positive control (n = 4). All dogs had uneventful healings following the surgery. Sequential polychrome fluorescent labeling, maxillofacial CT, microhardness tests, as well as histological and histomorphometric analyses indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically promoted bone formation and mineralization and maximally maintained the height and volume of elevated maxillary sinus. By comparison, both control groups of beta-TCP or autologous iliac bone showed considerable resorption and replacement by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely maintain the height and volume of the elevated sinus floor, and that the transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone formation and mineralization, maximally maintain height, volume and increase the compressive strength of augmented maxillary sinus. This tissue engineered bone complex might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation. PMID: 19761881 [PubMed - as supplied by publisher] |
| The effects of rhBMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora.
September 19, 2009 at 6:03 pm
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| | The effects of rhBMP-2 released from biodegradable polyurethane/microsphere composite scaffolds on new bone formation in rat femora. Biomaterials. 2009 Sep 15; Authors: Li B, Yoshii T, Hafeman AE, Nyman JS, Wenke JC, Guelcher SA Scaffolds prepared from biodegradable polyurethanes (PUR) have been investigated as a supportive matrix and delivery system for skin, cardiovascular, and bone tissue engineering. While previous studies have suggested that PUR scaffolds are biocompatible and moderately osteoconductive, the effects of encapsulated osteoinductive molecules, such as recombinant human bone morphogenetic protein (rhBMP-2), on new bone formation have not been investigated for this class of biomaterials. The objective of this study was to investigate the effects of different rhBMP-2 release strategies on new bone formation in PUR scaffolds implanted in rat femoral plug defects. In the simplest approach, rhBMP-2 was added as a dry powder prior to the foaming reaction, which resulted in a burst release of 35% followed by a sustained release for 21 days. Encapsulation of rhBMP-2 in either 1.3-micron or 114-micron PLGA microspheres prior to the foaming reaction reduced the burst release. At 4 weeks post-implantation, all rhBMP-2 treatment groups enhanced new bone formation relative to the scaffolds without rhBMP-2. Scaffolds incorporating rhBMP-2 powder promoted the most extensive new bone formation, while scaffolds incorporating rhBMP-2 encapsulated in 1.3-micron microspheres, which exhibited the lowest burst release, promoted the least extensive new bone formation. Thus our observations suggest that an initial burst release followed by sustained release is better for promoting new bone formation. PMID: 19762079 [PubMed - as supplied by publisher] |
| Cardiomyocytes from human pluripotent stem cells in regenerative medicine and drug discovery.
September 19, 2009 at 6:03 pm
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| | Cardiomyocytes from human pluripotent stem cells in regenerative medicine and drug discovery. Trends Pharmacol Sci. 2009 Sep 15; Authors: Braam SR, Passier R, Mummery CL Stem cells derived from pre-implantation human embryos or from somatic cells by reprogramming are pluripotent and self-renew indefinitely in culture. Pluripotent stem cells are unique in being able to differentiate to any cell type of the human body. Differentiation towards the cardiac lineage has attracted significant attention, initially with a strong focus on regenerative medicine. Although an important research area, the heart has proven challenging to repair by cardiomyocyte replacement. However, the ability to reprogramme adult cells to pluripotent stem cells and genetically manipulate stem cells presented opportunities to develop models of human disease. The availability of human cardiomyocytes from stem cell sources is expected to accelerate the discovery of cardiac drugs and safety pharmacology by offering more clinically relevant human culture models than presently available. Here we review the state-of-the-art using stem cell-derived human cardiomyocytes in drug discovery, drug safety pharmacology, and regenerative medicine. PMID: 19762090 [PubMed - as supplied by publisher] |
| Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells.
September 19, 2009 at 6:03 pm
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| | Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells. FASEB J. 2009 Sep 17; Authors: Bonde S, Pedram M, Stultz R, Zavazava N Bone marrow transplantation is a curative treatment for many diseases, including leukemia, autoimmune diseases, and a number of immunodeficiencies. Recently, it was claimed that bone marrow cells transdifferentiate, a much desired property as bone marrow cells are abundant and therefore could be used in regenerative medicine to treat incurable chronic diseases. Using a Cre/loxP system, we studied cell fusion after bone marrow transplantation. Fused cells were chiefly Gr-1(+), a myeloid cell marker, and found predominantly in the bone marrow; in parenchymal tissues. Surprisingly, fused cells were most abundant in the kidney, Peyer's patches, and cardiac tissue. In contrast, after cell fusion with embryonic stem cells, bone marrow cells were reprogrammed into new tetraploid pluripotent stem cells that successfully differentiated into beating cardiomyocytes. Together, these data suggest that cell fusion is ubiquitous after cellular transplants and that the subsequent sharing of genetic material between the fusion partners affects cellular survival and function. Fusion between tumor cells and bone marrow cells could have consequences for tumor malignancy.-Bonde, S., Pedram, M., Stultz, R., Zavazava, N. Cell fusion of bone marrow cells and somatic cell reprogramming by embryonic stem cells. PMID: 19762558 [PubMed - as supplied by publisher] |
| Isolation and differentiation of nestin positive cells from rat oral mucosal lamina propria.
September 19, 2009 at 6:03 pm
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| | Isolation and differentiation of nestin positive cells from rat oral mucosal lamina propria. Differentiation. 2009 Sep 15; Authors: Dong R, Liu X, Fan M, Yang L, Peng L, Zhang L Despite successes in the isolation and characterization of stem cells from the oral mucosal epithelium, there have been few studies on progenitor cells from the oral mucosal lamina propria. In this study, we isolate rat oral mucosal lamina propria cells (OMLPC) using nestin as a marker in an immunomagnetic sorting technique. The OMLPCs was negative for cytokeratin. Nestin and vimentin were expressed in the OMLPCs. And CD44 and STRO-1 were expressed in a subset of the OMLPCs, which suggest that the nestin positive OMLPCs be heterogeneous. Otherwise, OMLPCs express Oct4, which is a critical gene for pluripotency. The OMLPCs proliferated actively in vitro. A colony forming study demonstrated that OMLPCs exhibited colony-generating capacity. When cultured in defined medium, OMLPCs generated cells characteristic of osteoblast, adipocyte and astrocyte-like cells. In addition, OMLPCs seeded into three dimensional scaffolds form bone-like structures in vivo after 8 weeks. All of the results demonstrate that OMLPCs are a population of mesenchymal progenitor cells existing in rat oral mucosal lamina propria. Nestin is shown to be a useful molecular marker for these cells. In certain environments, OMLPCs can form hard tissue. Thus, OMLPCs may serve as a suitable source of cells for future bone or tooth tissue engineering applications. PMID: 19762142 [PubMed - as supplied by publisher] |
| Concurrent Vasculogenesis and Neurogenesis From Adult Neural Stem Cells.
September 19, 2009 at 6:03 pm
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| | Concurrent Vasculogenesis and Neurogenesis From Adult Neural Stem Cells. Circ Res. 2009 Sep 17; Authors: Ii M, Nishimura H, Sekiguchi H, Kamei N, Yokoyama A, Horii M, Asahara T Rationale: Recent reports have demonstrated that signals from vascular endothelial cells are necessary for organogenesis that may precede vasculogenesis. However, the origin of these neovascular cells in regenerating tissue has not been clarified. Objective: Here we tested the hypothesis that adult neural stem cells (NSCs) can differentiate into vascular lineage, as well as neural lineage, in the process of collaborative organogenesis. Methods and Results: NSCs, clonally isolated from mouse brain, were shown to develop endothelial and smooth muscle phenotypes in vitro. To elucidate whether NSCs can simultaneously differentiate into vascular and neural cells in vivo, genetically labeled NSCs were administered to mice with unilateral sciatic nerve crush injury or operatively induced brain and myocardial ischemia. Two weeks later, necropsy examination disclosed recruitment of the labeled NSCs to sites of injury differentiating into vascular cells (endothelial cells and vascular smooth muscle cells) and Schwann cells in regenerating nerve. Similarly, NSC-derived vascular cells/astrocytes and endothelial cells were identified in ischemic brain tissue and capillaries in myocardium 2 weeks following transplantation, respectively. Conclusions: These findings, concurrent vasculogenesis and neurogenesis from a common stem cell, suggest that certain somatic stem cells are capable of differentiating into not only somatic cells of identity but also into vascular cells for tissue regeneration. PMID: 19762683 [PubMed - as supplied by publisher] |
| Insulin-Like Growth Factor Binding Protein-3 Mediates Vascular Repair by Enhancing Nitric Oxide Generation.
September 19, 2009 at 6:03 pm
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| | Insulin-Like Growth Factor Binding Protein-3 Mediates Vascular Repair by Enhancing Nitric Oxide Generation. Circ Res. 2009 Sep 17; Authors: Kielczewski JL, Jarajapu Y, McFarland EL, Cai J, Afzal A, Li Calzi S, Chang KH, Lydic T, Shaw LC, Busik J, Hughes J, Cardounel AJ, Wilson K, Lyons TJ, Boulton ME, Mames RN, Chan-Ling T, Grant MB Rationale: Insulin-like growth factor binding protein (IGFBP)-3 modulates vascular development by regulating endothelial progenitor cell (EPC) behavior, specifically stimulating EPC cell migration. This study was undertaken to investigate the mechanism of IGFBP-3 effects on EPC function and how IGFBP-3 mediates cytoprotection following vascular injury. Objective: To examine the mechanism of IGFBP-3-mediated repair following vascular injury. Methods and Results: We used 2 complementary vascular injury models: laser occlusion of retinal vessels in adult green fluorescent protein (GFP) chimeric mice and oxygen-induced retinopathy in mouse pups. Intravitreal injection of IGFBP-3-expressing plasmid into lasered GFP chimeric mice stimulated homing of EPCs, whereas reversing ischemia induced increases in macrophage infiltration. IGFBP-3 also reduced the retinal ceramide/sphingomyelin ratio that was increased following laser injury. In the OIR model, IGFBP-3 prevented cell death of resident vascular endothelial cells and EPCs, while simultaneously increasing astrocytic ensheathment of vessels. For EPCs to orchestrate repair, these cells must migrate into ischemic tissue. This migratory ability is mediated, in part, by endogenous NO generation. Thus, we asked whether the migratory effects of IGFBP-3 were attributable to stimulation of NO generation. IGFBP-3 increased endothelial NO synthase expression in human EPCs leading to NO generation. IGFBP-3 exposure also led to the redistribution of vasodilator-stimulated phosphoprotein, an NO regulated protein critical for cell migration. IGFBP-3-mediated NO generation required high-density lipoprotein receptor activation and stimulation of phosphatidylinositol 3-kinase/Akt pathway. Conclusion: These studies support consideration of IGFBP-3 as a novel agent to restore the function of injured vasculature and restore NO generation. PMID: 19762684 [PubMed - as supplied by publisher] |
| Liver transplantation for hepatocellular carcinoma: the Japanese experience.
September 19, 2009 at 6:03 pm
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| | Liver transplantation for hepatocellular carcinoma: the Japanese experience. J Hepatobiliary Pancreat Surg. 2009 Sep 18; Authors: Furukawa H, Shimamura T, Suzuki T, Taniguchi M, Nakanishi K, Yamashita K, Kamiyama T, Matsushita M, Todo S Despite the wide spectrum of selection criteria used by living donor liver transplantation (LDLT) centers in Japan, LDLT for hepatocellular carcinoma (HCC) can achieve an acceptable outcome comparable to the outcome for deceased donor liver transplantation (DDLT) for HCC. One of the most crucial considerations in liver transplantation for HCC is the advent of expanded criteria that allow more patients with HCC to receive the organs and offer similar or even better results compared to the Milan of UCSF criteria. Expanded criteria for HCC are proposed from three single-center and one multicenter study in Japan. These criteria are based on the independent predictors for outcome derived from the analyses of the pretransplant factors and explant pathology. The beneficial effect of those proposed criteria can be predicted by the inclusion rates of the patients compared to the Milan or UCSF criteria in the same cohort and the outcome for those included patients. While application of the UCSF criteria increases the inclusion rate compared to the Milan criteria by 5-10%, these proposed criteria increase the inclusion rates by 5-54% compared to the Milan criteria. The higher inclusion rates compared to the application of the Milan criteria are achieved by criteria including tumor markers, either AFP or PIVKA II or both. Inclusion of tumor markers in addition to parameters of tumor morphology might be the key to establish the best criteria for liver transplantation for HCC. PMID: 19763387 [PubMed - as supplied by publisher] |
| Synthesis and Characterization of Elastin-Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties.
September 19, 2009 at 6:03 pm
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| | Synthesis and Characterization of Elastin-Mimetic Hybrid Polymers with Multiblock, Alternating Molecular Architecture and Elastomeric Properties. Macromolecules. 2009 Apr;42(7):2532-2541 Authors: Grieshaber SE, Farran AJ, Lin-Gibson S, Kiick KL, Jia X We are interested in developing elastin-mimetic hybrid polymers (EMHPs) that capture the multiblock molecular architecture of tropoelastin as well as the remarkable elasticity of mature elastin. In this study, multiblock EMHPs containing flexible synthetic segments based on poly(ethylene glycol) (PEG) alternating with alanine-rich, lysine-containing peptides were synthesized by step-growth polymerization using alpha,omega-azido-PEG and alkyne-terminated AKA(3)KA (K = lysine, A = alanine) peptide, employing orthogonal click chemistry. The resulting EMHPs contain an estimated three to five repeats of PEG and AKA(3)KA and have an average molecular weight of 34 kDa. While the peptide alone exhibited alpha-helical structures at high pH, the fractional helicity for EMHPs was reduced. Covalent cross-linking of EMHPs with hexamethylene diisocyanate (HMDI) through the lysine residue in the peptide domain afforded an elastomeric hydrogel (xEMHP) with a compressive modulus of 0.12 MPa when hydrated. The mechanical properties of xEMHP are comparable to a commercial polyurethane elastomer (Tecoflex SG80A) under the same conditions. In vitro toxicity studies showed that while the soluble EMHPs inhibited the growth of primary porcine vocal fold fibroblasts (PVFFs) at concentrations >/=0.2 mg/mL, the cross-linked hybrid elastomers did not leach out any toxic reagents and allowed PVFFs to grow and proliferate normally. The hybrid and modular approach provides a new strategy for developing elastomeric scaffolds for tissue engineering. PMID: 19763157 [PubMed - as supplied by publisher] |
| Combined Therapy With Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cells Increases Benefits in Infarcted Swine Hearts.
September 19, 2009 at 6:03 pm
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| | Combined Therapy With Simvastatin and Bone Marrow-Derived Mesenchymal Stem Cells Increases Benefits in Infarcted Swine Hearts. Arterioscler Thromb Vasc Biol. 2009 Sep 17; Authors: Yang YJ, Qian HY, Huang J, Li JJ, Gao RL, Dou KF, Yang GS, Willerson JT, Geng YJ OBJECTIVE: Widespread death of implanted cells hampers stem cell therapy for acute myocardial infarction (AMI). Based on the pleiotropic beneficial effects of statins, we examined whether simvastatin (SIMV) increased the efficacy of mesenchymal stem cell (MSC) transplantation after AMI. METHODS AND RESULTS: Chinese miniswine (n=28) were randomized to 1 of 4 groups (n=7 per group): control, SIMV (0.25 mg/kg . d), MSC transplantation, and SIMV+MSCs. AMI was created by ligating the left anterior descending coronary; MSCs were injected immediately into the cyanotic myocardium. At 6 weeks, MRI showed the number of dyskinetic segments and the infarct size were significantly decreased in the SIMV group. Cardiac function improved and the perfusion defect decreased significantly in the SIMV+MSC group but not in the MSC-only group (P<0.05, versus control group). MSC survival and differentiation were significantly better in the combination group than in the MSC-only group (P<0.01). Cell apoptosis decreased significantly in both the SIMV and the SIMV+MSC groups but not in the MSC-only group when compared with controls (P<0.05). Furthermore, oxidative stress and inflammatory response was significantly reduced in the infarcted regions in both the SIMV and the SIMV+MSCs groups. CONCLUSIONS: SIMV treatment improves the therapeutic efficacy of MSC transplantation in acutely infarcted hearts by promoting cell survival and cardiovascular differentiation. PMID: 19762786 [PubMed - as supplied by publisher] |
| Stem cell-like human endothelial progenitors show enhanced colony-forming capacity after brief sevoflurane exposure: preconditioning of angiogenic cells by volatile anesthetics.
September 19, 2009 at 6:03 pm
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| | Stem cell-like human endothelial progenitors show enhanced colony-forming capacity after brief sevoflurane exposure: preconditioning of angiogenic cells by volatile anesthetics. Anesth Analg. 2009 Oct;109(4):1117-26 Authors: Lucchinetti E, Zeisberger SM, Baruscotti I, Wacker J, Feng J, Zaugg K, Dubey R, Zisch AH, Zaugg M BACKGROUND: Endothelial progenitor cells play a pivotal role in tissue repair, and thus are used for cell replacement therapies in "regenerative medicine." We tested whether the anesthetic sevoflurane would modulate growth or mobilization of these angiogenic cells. METHODS: In an in vitro model, mononuclear cells isolated from peripheral blood of healthy donors were preconditioned with sevoflurane (3 times 30 min at 2 vol% interspersed by 30 min of air). Colony-forming units were determined after 9 days in culture and compared with time-matched untreated control. Using magnetic cell sorting, CD133+/CD34+ endothelial progenitors were enriched from human umbilical cord blood, and vascular endothelial growth factor (VEGF), VEGFR2 (KDR), granulocyte colony-stimulating factor (G-CSF), STAT3, c-kit, and CXCR4 expressions were determined in sevoflurane-treated and untreated cells by real-time reverse transcriptase polymerase chain reaction. In a volunteer study with crossover design, we tested whether sevoflurane inhalation (<1 vol% end-tidal concentration) would mobilize endothelial progenitor cells from the bone marrow niche into the circulation using flow cytometry of peripheral blood samples. VEGF and G-CSF plasma levels were also measured. RESULTS: In vitro sevoflurane exposure of mononuclear cells enhanced colony-forming capacity and increased VEGF mRNA levels in CD133+/CD34+ cord blood cells (P = 0.017). Sevoflurane inhalation in healthy volunteers did not alter the number of CD133+/CD34+ or KDR+/CD34+ endothelial progenitors in the circulation, but increased the number of colony-forming units (P = 0.034), whereas VEGF and G-CSF plasma levels remained unchanged. CONCLUSIONS: Sevoflurane preconditioning promotes growth and proliferation of stem cell-like human endothelial progenitors. Hence, it may be used to promote perioperative vascular healing and to support cell replacement therapies. PMID: 19762739 [PubMed - in process] |
| Autologous chondrocyte implantation in the knee using fibrin.
September 19, 2009 at 6:03 pm
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| | Autologous chondrocyte implantation in the knee using fibrin. Knee Surg Sports Traumatol Arthrosc. 2009 Sep 18; Authors: Kim MK, Choi SW, Kim SR, Oh IS, Won MH Autologous chondrocyte implantation (ACI) is widely used to treat symptomatic articular cartilage injury of the knee. Fibrin ACI is a new tissue-engineering technique for the treatment of full-thickness articular cartilage defects, in which autologous chondrocytes are inserted into a three-dimensional scaffold provided by fibrin gel. The objective of this study is to document and compare mean changes in overall clinical scores at both baseline and follow-up. Fibrin ACI was used to treat deep cartilage defects of the femoral condyle in 30 patients. There were 24 men and 6 women with a median age of 35 years (range 15-55) and with a mean defect size of 5.8 cm(2) (range 2.3-12). Clinical and functional knee evaluations were performed using different scoring systems, MRI was performed 24 months postoperatively, and arthroscopy was performed 12 months postoperatively. All patients achieved clinical and functional status improvements following surgery (P < 0.01). The mean scores of the Henderson classification (MRI evaluation) significantly improved from 14.4 to 7 (P = 0.001), and no graft-associated complications were noted. Arthroscopic assessments performed 12 months postoperatively produced nearly normal (grade II) International Cartilage Repair Society scores in 8 of the 10 study patients. Fibrin ACI offers the advantages of technical simplicity, minimal invasiveness, a short surgery time, and easier access to difficult sites than classical ACI. Based on the findings of this clinical pilot study, we conclude that fibrin ACI offers a reliable means of treating articular cartilage defects of the knee. PMID: 19763540 [PubMed - as supplied by publisher] |
| Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility.
September 19, 2009 at 6:03 pm
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| | Construction of collagen II/hyaluronate/chondroitin-6-sulfate tri-copolymer scaffold for nucleus pulposus tissue engineering and preliminary analysis of its physico-chemical properties and biocompatibility. J Mater Sci Mater Med. 2009 Sep 18; Authors: Li CQ, Huang B, Luo G, Zhang CZ, Zhuang Y, Zhou Y To construct a novel scaffold for nucleus pulposus (NP) tissue engineering, The porous type II collagen (CII)/hyaluronate (HyA)-chondroitin-6-sulfate (6-CS) scaffold was prepared using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross-linking system. The physico-chemical properties and biocompatibility of CII/HyA-CS scaffolds were evaluated. The results suggested CII/HyA-CS scaffolds have a highly porous structure (porosity: 94.8 +/- 1.5%), high water-binding capacity (79.2 +/- 2.8%) and significantly improved mechanical stability by EDC/NHS crosslinking (denaturation temperature: 74.6 +/- 1.8 and 58.1 +/- 2.6 degrees C, respectively, for the crosslinked scaffolds and the non-crosslinked; collagenase degradation rate: 39.5 +/- 3.4 and 63.5 +/- 2.0%, respectively, for the crosslinked scaffolds and the non-crosslinked). The CII/HyA-CS scaffolds also showed satisfactory cytocompatibility and histocompatibility as well as low immunogenicity. These results indicate CII/HyA-CS scaffolds may be an alternative material for NP tissue engineering due to the similarity of its composition and physico-chemical properties to those of the extracellular matrices (ECM) of native NP. PMID: 19763796 [PubMed - as supplied by publisher] |
| A detailed characterization of the adult mouse model of glycogen storage disease Ia.
September 19, 2009 at 1:03 pm
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| | A detailed characterization of the adult mouse model of glycogen storage disease Ia. Lab Invest. 2009 Sep;89(9):1032-42 Authors: Salganik SV, Weinstein DA, Shupe TD, Salganik M, Pintilie DG, Petersen BE Glycogen storage disease type Ia (GSDIa) is caused by a genetic defect in the hepatic enzyme glucose-6-phosphatase (G6Pase-alpha), which manifests as life-threatening hypoglycemia with related metabolic complications. A G6Pase-alpha knockout (KO) mouse model was generated to study potential therapies for correcting this disorder. Since then, gene therapy studies have produced promising results, showing long-term improvement in liver histology and glycogen metabolism. Under existing protocols, however, untreated KO pups seldom survived weaning. Here, we present a thorough characterization of the G6Pase-alpha KO mouse, as well as the husbandry protocol for rearing this strain to adulthood. These mice were raised with only palliative care, and characterized from birth through 6 months of age. Once KO mice have survived the very frail weaning period, their size, agility, serum lipids and glycemic control improve dramatically, reaching levels approaching their wild-type littermates. In addition, our data reveal that adult mice lacking G6Pase-alpha are able to mate and produce viable offspring. However, liver histology and glycogen accumulation do not improve with age. Overall, the reliable production of mature KO mice could provide a critical tool for advancing the GSDIa field, as the availability of a robust enzyme-deficient adult offers a new spectrum of treatment avenues that would not be tolerated by the frail pups. Most importantly, our detailed characterization of the adult KO mouse provides a crucial baseline for accurately gauging the efficacy of experimental therapies in this important model. PMID: 19581879 [PubMed - indexed for MEDLINE] | | | 
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