| A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response. November 4, 2009 at 6:27 am |
| | A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response. J Diabetes Sci Technol. 2008 Nov;2(6):1003-1015 Authors: Onuki Y, Bhardwaj U, Papadimitrakopoulos F, Burgess DJ In recent years, a variety of devices (drug-eluting stents, artificial organs, biosensors, catheters, scaffolds for tissue engineering, heart valves, etc.) have been developed for implantation into patients. However, when such devices are implanted into the body, the body can react to these in a number of different ways. These reactions can result in an unexpected risk for patients. Therefore, it is important to assess and optimize the biocompatibility of implantable devices. To date, numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. This review focuses on the foreign body response and the approaches that have been taken to overcome this. The biological response following device implantation and the methods for biocompatibility evaluation are summarized. Then the risks of implantable devices and the challenges to overcome these problems are introduced. Specifically, the challenges used to overcome the functional loss of glucose sensors, restenosis after stent implantation, and calcification induced by implantable devices are discussed. PMID: 19885290 [PubMed - as supplied by publisher] |
| Stem cells in gastroenterology and hepatology. November 4, 2009 at 6:27 am |
| | Stem cells in gastroenterology and hepatology. Nat Rev Gastroenterol Hepatol. 2009 Nov 3; Authors: Quante M, Wang TC Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use of stem cells in regenerative medicine and treatments for disease. Embryonic stem cells and induced pluripotent stem cells have the potential to give rise to any cell type in the human body, but their therapeutic application remains challenging. The use of adult or tissue-restricted stem cells is emerging as another possible approach for the treatment of gastrointestinal diseases. The same self-renewal properties that allow stem cells to remain immortal and generate any tissue can occasionally make their proliferation difficult to control and make them susceptible to malignant transformation. This Review provides an overview of the different types of stem cell, focusing on tissue-restricted adult stem cells in the fields of gastroenterology and hepatology and summarizing the potential benefits and risks of using stems cells to treat gastroenterological and liver disorders. PMID: 19884893 [PubMed - as supplied by publisher] |
| Regenerative Medicine Special Feature: Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. November 4, 2009 at 6:27 am |
| | Regenerative Medicine Special Feature: Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury. Proc Natl Acad Sci U S A. 2009 Nov 2; Authors: Lee H, McKeon RJ, Bellamkonda RV Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 degrees C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection-prone, and clinically problematic. To overcome this limitation, we have thermostabilized chABC and developed a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Thermostabilized chABC remained active at 37 degrees C in vitro for up to 4 weeks. CSPG levels remained low in vivo up to 6 weeks post-SCI when thermostabilized chABC was delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chABC versus a single treatment of unstabilized chABC demonstrated significant differences in CSPG digestion. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery showed significant improvement in locomotor function and enhanced growth of cholera toxin B subunit-positive sensory axons and sprouting of serotonergic fibers. Therefore, improving chABC thermostability facilitates minimally invasive, sustained, local delivery of chABC that is potentially effective in overcoming CSPG-mediated regenerative failure. Combination therapy with thermostabilized chABC with neurotrophic factors enhances axonal regrowth, sprouting, and functional recovery after SCI. PMID: 19884507 [PubMed - as supplied by publisher] |
| What's New in Orthopaedic Research. November 4, 2009 at 6:27 am |
| | What's New in Orthopaedic Research. J Bone Joint Surg Am. 2009 Nov;91-A(11):2756-2770 Authors: Hidaka C, Maher S, Packer J, Gasinu S, Cunningham ME, Rodeo S PMID: 19884457 [PubMed - as supplied by publisher] |
| Commitment of stem cells into functional hepatocytes. November 4, 2009 at 6:27 am |
| | Commitment of stem cells into functional hepatocytes. Differentiation. 2009 Oct 31; Authors: Ochiya T, Yamamoto Y, Banas A Liver transplants represent the only way to treat patients suffering from terminal liver failure, but they are associated with numerous problems, including a chronic shortage of donors, high cost, rejection, and side effects for the donor. It is anticipated that regenerative medicine will provide an alternative to liver transplants for such patients. Regenerative medicine refers to the academic field of eliciting the inherent capacity of organisms for self-regeneration to the greatest possible extent in order to develop new methods of treatment for intractable disorders. From this perspective, much is expected from the use of human embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells), and the vigorous development of technology to induce the differentiation of such stem cells into cells possessing hepatic functions is underway. Clinical applications of these human stem cells, however, have yet to reach even the earliest stages of implementation. Facing off against these versatile ES cells are stem cells derived from somatic cells present within organisms, which are attracting attention owing to their superiority in terms of ethics and safety, with many research institutes now in the process of elucidating the details of stem cell separation and identification as well as their plasticity and pluripotency. Bone marrow cells are the best-known somatic-cell-derived stem cells, but the use of mesenchymal stem cells (MSCs) found in adipose tissue has also recently attracted attention. This paper will review the differentiation ability and mechanisms of these various stem cell types to hepatocytes and their application to liver regeneration and the future outlook. PMID: 19883970 [PubMed - as supplied by publisher] |
| Endothelial Differentiation of Adipose-Derived Stem Cells: Effects of Endothelial Cell Growth Supplement and Shear Force. November 4, 2009 at 6:27 am |
| | Endothelial Differentiation of Adipose-Derived Stem Cells: Effects of Endothelial Cell Growth Supplement and Shear Force. J Surg Res. 2009 Mar;152(1):157-166 Authors: Fischer LJ, McIlhenny S, Tulenko T, Golesorkhi N, Zhang P, Larson R, Lombardi J, Shapiro I, Dimuzio PJ BACKGROUND: Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ASC). Herein we study the effects of endothelial cell growth supplement (ECGS) and physiological shear force on the differentiation of ASC into endothelial cells. MATERIALS AND METHODS: Human ASC (CD13(+)29(+)90(+)31(-)45(-)) were isolated from periumbilical fat, cultured in ECGS media (for up to 3 wk), and exposed to physiological shear force (12 dynes for up to 8 d) in vitro. Endothelial phenotype was defined by cord formation on Matrigel, acetylated-low density lipoprotein (acLDL) uptake, and expression of nitric oxide synthase (eNOS), von Willebrand factor (vWF), and CD31 (platelet endothelial cell adhesion molecule, PECAM). Additionally, cell thrombogenicity was evaluated by seeding canine autologous ASC onto vascular grafts implanted within the canine arterial circulation for 2 wk. RESULTS: We found that undifferentiated ASC did not display any of the noted endothelial characteristics. After culture in ECGS, ASC formed cords in Matrigel but failed to take up acLDL or express the molecular markers. Subsequent exposure to shear resulted in stem cell realignment, acLDL uptake, and expression of CD31; eNOS and vWF expression was still not observed. Grafts seeded with cells grown in ECGS (+/- shear) remained patent (six of seven) at 2 wk but had a thin coat of fibrin along the luminal surfaces. CONCLUSIONS: This study suggests that (1) ECGS and shear promote the expression of several endothelial characteristics in human adipose-derived stem cells, but not eNOS or vWF; (2) their combined effects appear synergistic; and (3) stem cells differentiated in ECGS appear mildly thrombogenic in vitro, possibly related, in part, to insufficient eNOS expression. Thus, while the acquisition of several endothelial characteristics by adult stem cells derived from adipose tissue suggests these cells are a viable source of autologous cells for cardiovascular regeneration, further stimulation/modifications are necessary prior to using them as a true endothelial cell replacement. PMID: 19883577 [PubMed - as supplied by publisher] |
| Laser Printing of Skin Cells and Human Stem Cells. November 4, 2009 at 6:27 am |
| | Laser Printing of Skin Cells and Human Stem Cells. Tissue Eng Part C Methods. 2009 Nov 2; Authors: Koch L, Kuhn S, Sorg H, Gruene M, Schlie S, Gaebel R, Polchow B, Reimers K, Stoelting S, Ma N, Vogt P, Steinhoff G, Chichkov BN Laser printing based on laser-induced forward transfer (LIFT) is a new biofabrication technique for the arrangement of biological materials or living cells in well-defined patterns. In the current study, skin cell lines (fibroblasts/keratinocytes) and human mesenchymal stem cells (hMSC) were chosen for laser printing experiments due to their high potential in regeneration of human skin and new application possibilities of stem cell therapy. To evaluate the influence of LIFT on the cells, their survival rate, their proliferation and apoptotic activity, as well as DNA damages and modifications of their cell surface markers, were assessed and statistically evaluated over several days. The cells survived the transfer procedure with a rate of 98% +/- 1% SEM (skin cells) and 90% +/- 10% (hMSC), respectively. All used cell types maintain their ability to proliferate after LIFT. Furthermore, skin cells and hMSC did not show an increase of apoptosis or DNA fragmentation. In addition, the hMSC keep their phenotype as proven by FACS analysis. This study demonstrates LIFT as a suitable technique for unharmed computer-controlled positioning of different cell types and a promising tool for future applications in the ex vivo generation of tissue replacements. PMID: 19883209 [PubMed - as supplied by publisher] |
| [Stem cell therapy: an update] November 4, 2009 at 6:27 am |
| | [Stem cell therapy: an update] Bull Acad Natl Med. 2009 Mar;193(3):535-6 Authors: Coulombel L Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood PMID: 19883007 [PubMed - in process] | | |
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| The Podesta Watch: White House Visits, Red Shoes and 61 Percent Gains November 4, 2009 at 5:18 pm |
| | Tony Podesta, the California stem cell agency's man on the Potomac, is making news again, largely for flashy fundraising and access to the Obama White House.Podesta was hired as a federal lobbyist by CIRM last February under a 10-month, $240,000 contract. California state agencies, rarely if ever, hire federal lobbyists, although the state does maintain a lobbyist on the state payroll in | | | | |
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| Scientist Magazine Picks Up Grant Termination Story November 3, 2009 at 7:32 pm |
| | The Scientist magazine today picked up our report on the termination of three grants by the California stem cell agency. In a piece by Jef Akst, the magazine said CIRM "giveth and it taketh away."The Scientist piece, which credited the California Stem Cell Report, did not add a great deal to our report, but Akst wrote,"'Termination is a last option,'" CIRM's chief communications officer Don |
| Nature on Disease Team Round: The Race is On November 3, 2009 at 7:05 pm |
| | Nature magazine has published another piece on the California stem cell agency's ambitious, $230 million disease team round, calling it the "starting gun" to confirm the promise of stem cells.The Nov. 2, 2009, story by Erika Check Hayden said that some researchers around the country say the grants and loans will benefit the field as a whole. She also carried a comment from the former chairman of |
| Correction November 3, 2009 at 7:04 pm |
| | The "stem cell web" item Nov. 1, 2009, incorrectly reported that only one reporter was present at the CIRM disease team news conference, based on information provided by a person who was also present. CIRM says two other reporters from local outlets were also on the scene. |
| StemCells, Inc. Closes $12.5 Million Equity Financing November 3, 2009 at 10:50 am |
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| Stem Cell Therapy International, Inc. and Histostem Korea Announce $5 Million Financing Commitment November 3, 2009 at 10:50 am |
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| Stem Cell Research Bringing Jobs and Innovation to Ontario, Canada November 3, 2009 at 9:50 am |
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| Entest BioMedical Signs LOI with Quantum Advisors to Coordinate Development of COPD Stem Cell Therapy November 3, 2009 at 8:50 am |
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| Dose-dependent Efficacy of ALS-human Mesenchymal Stem Cells Transplantation into Cisterna Magna in SOD1-G93A ALS mice. November 3, 2009 at 7:41 am |
| | Dose-dependent Efficacy of ALS-human Mesenchymal Stem Cells Transplantation into Cisterna Magna in SOD1-G93A ALS mice. Neurosci Lett. 2009 Oct 28; Authors: Kim H, Kim HY, Choi MR, Hwang S, Nam KH, Kim HC, Han JS, Kim KS, Kim SH Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Although the underlying cause of the disease remains unclear, a variety of pathogenic mechanisms have been proposed. Despite promising preclinical studies showing the modification of the disease progression, most trials have failed to demonstrate any significant improvement in outcome. Stem cell therapy therefore has been proposed as an alternative therapy for ALS. In this study, we evaluated the dose-dependent effects of human bone marrow mesenchymal stem cells (hMSCs) obtained from an ALS patient (ALS-hMSCs) on SOD1 mice via intrathecal injection and showed its practicality for hMSCs. We transplanted different doses (1x10(4), 2x10(5), and 1x10(6)) of ALS-hMSCs into the cisterna magna and performed clinical observations including symptom onset, survival time, and locomotor performance using the rotarod test. Nissl staining was performed to evaluate motor neurons in lumbar spinal cord sections at 109 days, and transplanted cells were evaluated by immuno-fluorescence staining at the end stage. A cell dose of 1x10(6) cells significantly prolonged life span and delayed the decline of motor performance. At this dose, the average number of motor neurons was significantly higher than those of the untreated and 1x10(4) cell treated groups. Most injected hMSCs distributed in the ventricular system and subarachnoid space, while some migrated into the brain and spinal cord. These data suggest that intrathecal injection with an optimized cell number could be a potential route for stem cell therapy in ALS patients. PMID: 19879334 [PubMed - as supplied by publisher] |
| [The development of plastic surgery : Retrospective view of 80 years of "Der Chirurg" (The Surgeon).] November 3, 2009 at 7:28 am |
| | [The development of plastic surgery : Retrospective view of 80 years of "Der Chirurg" (The Surgeon).] Chirurg. 2009 Nov 1; Authors: Horch RE The often groundbreaking developments of new methods in Plastic Surgery have been published in the journal "Der Chirurg" (The Surgeon) ever since its foundation in 1928, when it was established as a journal dealing with all aspects of surgery and containing many innovations and developments. Historically this is also reflected in the establishment of Plastic Surgery initially as a subspecialty and later on as a specialty within the German Society for Surgery. The interdisciplinary character of modern reconstructive and oncological concepts, not only with other specialties but also within various surgical specialties, raises further challenges and leads to new developments in reconstruction, which will definitely induce an increasing amount of knowledge to the advantage of our patients. Scientific and clinical advances over the last 80 years give rise to the hope that similar success will be attained for reconstruction of traumatic and oncological defects and malformations or disfigurations in the future. Consolidated findings from regenerative medicine and tissue engineering will enrich the daily practice of surgical reconstruction. PMID: 19882333 [PubMed - as supplied by publisher] |
| Isolation, characterization and osteogenic differentiation of adipose-derived stem cells: from small to large animal models. November 3, 2009 at 7:28 am |
| | Isolation, characterization and osteogenic differentiation of adipose-derived stem cells: from small to large animal models. Cell Tissue Res. 2009 Oct 31; Authors: Arrigoni E, Lopa S, de Girolamo L, Stanco D, Brini AT One of the most important issues in orthopaedic surgery is the loss of bone resulting from trauma, infections, tumours or congenital deficiency. In view of the hypothetical future application of mesenchymal stem cells isolated from human adipose tissue in regenerative medicine, we have analysed and characterized adipose-derived stem cells (ASCs) isolated from adipose tissue of rat, rabbit and pig. We have compared their in vitro osteogenic differentiation abilities for exploitation in the repair of critical osteochondral defects in autologous pre-clinical models. The number of pluripotent cells per millilitre of adipose tissue is variable and the yield of rabbit ASCs is lower than that in rat and pig. However, all ASCs populations show both a stable doubling time during culture and a marked clonogenic ability. After exposure to osteogenic stimuli, ASCs from rat, rabbit and pig exhibit a significant increase in the expression of osteogenic markers such as alkaline phosphatase, extracellular calcium deposition, osteocalcin and osteonectin. However, differences have been observed depending on the animal species and/or differentiation period. Rabbit and porcine ASCs have been differentiated on granules of clinical grade hydroxyapatite (HA) towards osteoblast-like cells. These cells grow and adhere to the scaffold, with no inhibitory effect of HA during osteo-differentiation. Such in vitro studies are necessary in order to select suitable pre-clinical models to validate the use of autologous ASCs, alone or in association with proper biomaterials, for the repair of critical bone defects. PMID: 19882172 [PubMed - as supplied by publisher] |
| The cyclooxygenase-2-selective inhibitor, etodolac, but not aspirin reduces neovascularization in a murine ischemic hind limb model. November 3, 2009 at 7:28 am |
| | The cyclooxygenase-2-selective inhibitor, etodolac, but not aspirin reduces neovascularization in a murine ischemic hind limb model. Eur J Pharmacol. 2009 Oct 29; Authors: Tanaka K, Yamamoto Y, Tsujimoto S, Uozumi N, Kita Y, Yoshida A, Shimizu T, Hisatome I Cyclooxygenase inhibitors are often prescribed to relieve severe ischemic leg pain in critical ischemic limb patients. Prescription of high doses of aspirin and selective cyclooxygenase-2 inhibitors is reported to increase cardiovascular events through suppression of the vaso-dilative prostanoid prostaglandin I(2) in endothelium. Here, we evaluated the influence of aspirin and etodolac, a selective cyclooxygenase-2 inhibitor, on neovascularization using a murine ischemia hind limb model. C57BL/6J mice were treated with aspirin or etodolac for twenty-eight days after induction of ischemia. We exploited a concentration of the agents that suppressed cyclooxygenase activity efficiently, especially in prostaglandin I(2) production. Recovery of limb blood perfusion and capillary density in ischemic limbs were significantly suppressed by etodolac treatment when compared to the aspirin treated group and untreated group. Production of 6-keto prostaglandin F(1alpha) and prostaglandin E(2) was lower in the aspirin treated group when compared with the etodolac treated group. Also, these concentrations were lower in both treatment groups compared with the untreated group. Immunohistochemical analysis suggested cyclooxygenase-2 was expressed in endothelium but not in inflammatory cells in ischemic tissue from the acute to chronic phase. Cyclooxygenase-1 was expressed strongly in inflammatory cells in the acute phase. Furthermore, bone-marrow-derived mononuclear cell transplantation improved neovascularization, whereas aspirin and etodolac did not inhibit these effects. Production of arachidonic acid metabolites by transplanted cells was independent of the improvement of neovascularization. In conclusion, cyclooxygenase-2 inhibition reduces ischemia-induced neovascularization. PMID: 19879866 [PubMed - as supplied by publisher] |
| Retinoic Acid from the meninges regulates cortical neuron generation. November 3, 2009 at 7:28 am |
| | Retinoic Acid from the meninges regulates cortical neuron generation. Cell. 2009 Oct 30;139(3):597-609 Authors: Siegenthaler JA, Ashique AM, Zarbalis K, Patterson KP, Hecht JH, Kane MA, Folias AE, Choe Y, May SR, Kume T, Napoli JL, Peterson AS, Pleasure SJ Extrinsic signals controlling generation of neocortical neurons during embryonic life have been difficult to identify. In this study we demonstrate that the dorsal forebrain meninges communicate with the adjacent radial glial endfeet and influence cortical development. We took advantage of Foxc1 mutant mice with defects in forebrain meningeal formation. Foxc1 dosage and loss of meninges correlated with a dramatic reduction in both neuron and intermediate progenitor production and elongation of the neuroepithelium. Several types of experiments demonstrate that retinoic acid (RA) is the key component of this secreted activity. In addition, Rdh10- and Raldh2-expressing cells in the dorsal meninges were either reduced or absent in the Foxc1 mutants, and Rdh10 mutants had a cortical phenotype similar to the Foxc1 null mutants. Lastly, in utero RA treatment rescued the cortical phenotype in Foxc1 mutants. These results establish RA as a potent, meningeal-derived cue required for successful corticogenesis. PMID: 19879845 [PubMed - in process] |
| Induction of EPC homing on biofunctionalized vascular grafts for rapid in vivo self-endothelialization - A review of current strategies. November 3, 2009 at 7:28 am |
| | Induction of EPC homing on biofunctionalized vascular grafts for rapid in vivo self-endothelialization - A review of current strategies. Biotechnol Adv. 2009 Oct 28; Authors: Avci-Adali M, Ziemer G, Wendel HP For years intensive research has been done to improve the hemocompatibility of blood contacting vascular devices. Despite the enormous progress in physicochemical surface optimization technologies, the native endothelium still represents the ideal surface for blood contact. Numerous tissue engineering strategies aspired towards the endothelialization of graft surfaces to generate a non-thrombogenic barrier on artificial materials. A paradigm change in surface modification concepts is the in vivo endothelialization of vascular grafts by capturing circulating endothelial progenitor cells (EPCs) directly from the blood stream via biofunctionalized implant materials. Thereby, capture molecules are immobilized on artificial vascular grafts to mimic a pro-homing substrate for EPCs. In this review, different coating strategies for in vivo capturing of EPCs on synthetic implants are discussed. This therapeutic concept opens a new chapter in regenerative medicine by realizing the vision that every patient seeds his implants with his own progenitor cells to make the synthetic grafts unrecognizable for the body's rejection mechanisms. PMID: 19879347 [PubMed - as supplied by publisher] |
| Utility of telomerase-pot1 fusion protein in vascular tissue engineering. November 3, 2009 at 7:28 am |
| | Utility of telomerase-pot1 fusion protein in vascular tissue engineering. Cell Transplant. 2009 Oct 29; Authors: Petersen TH, Hitchcock T, Muto A, Calle EA, Zhao L, Gong Z, Gui L, Dardik A, Bowles DE, Counter CM, Niklason LE While advances in regenerative medicine and vascular tissue engineering have been substantial in recent years, important stumbling blocks remain. In particular, the limited lifespan of differentiated cells that are harvested from elderly human donors is an important limitation in many areas of regenerative medicine. Recently, a mutant of the human telomerase reverse transcriptase enzyme (TERT) was described, which is highly processive and elongates telomeres more rapidly than conventional telomerase. This mutant, called pot1-TERT, is a chimeric fusion between the DNA binding protein pot1 and TERT. Because pot1-TERT is highly processive, it is possible that transient delivery of this transgene to cells that are utilized in regenerative medicine applications may elongate telomeres and extend cellular lifespan while avoiding risks that are associated with retroviral or lentiviral vectors. In the present study, adenoviral delivery of pot1-TERT resulted in transient reconstitution of telomerase activity in human smooth muscle cells, as demonstrated by telomeric repeat amplification protocol (TRAP). In addition, human engineered vessels that were cultured using pot1-TERT expressing cells had greater collagen content and somewhat better performance in vivo than control grafts. Hence, transient delivery of pot1-TERT to elderly human cells may be useful for increasing cellular lifespan and improving the functional characteristics of resultant tissue engineered constructs. PMID: 19878625 [PubMed - as supplied by publisher] |
| The clonogenic potential of hematopoietic stem cells and mesenchymal stromal cells in various hematologic diseases: a pilot study. November 3, 2009 at 7:28 am |
| | The clonogenic potential of hematopoietic stem cells and mesenchymal stromal cells in various hematologic diseases: a pilot study. Cytotherapy. 2009 Nov 2; Authors: Yüksel MK, Topçuoğlu P, Kurdal M, Ilhan O Abstract Background aims. Mesenchymal stromal cells (MSC) are the most popular cells used in regenerative medicine and biotechnology. The clonogenic potential of these cells is defined by colony-forming unit-fibroblasts (CFU-F). It is well known that there is an interaction between hematopoietic cells and stromal cells in disease formation pathogenesis. Therefore we hypothesized that there should be a quantitative and qualitative relationship between MSC colonies (CFU-F) and hematopoietic stem cell colonies (colony-forming unit-granulocyte-macrophages; CFU-GM) among patients with and without hematologic diseases. Methods. Forty-two patients were included in this study. Patients were divided into three groups: group A, patients with hematologic malignancies (n=20); group B, patients with bone marrow (BM) failure (n=11); group C, patients without hematologic diseases (n=11). BM aspirates were plated in different densities for CFU-F culture. The plating density was the same for CFU-GM culture. Results. CFU-GM colonies grew in 90% of group A cells and all of group B and C cells (P=0.0001). CFU-F colonies became visible on the ninth day of plating in group A and on the eight day in groups B and C. There was no statistically significant difference between the groups for the duration of CFU-F colony formation (P=0.12). There were differences in the morphology of the colonies among the groups. Conclusions. This is the first study that has compared the clonogenic potential of stromal cells and hematopoietic stem cells in the same subjects with and without hematologic diseases. No correlation was shown between the clonogenic potential of stromal cells and hematopoietic cells. PMID: 19878078 [PubMed - as supplied by publisher] |
| Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions. November 3, 2009 at 7:28 am |
| | Efficient expansion of mesenchymal stromal cells from umbilical cord under low serum conditions. Cytotherapy. 2009;11(6):738-48 Authors: Girdlestone J, Limbani VA, Cutler AJ, Navarrete CV Background Mesenchymal stromal cells (MSC) are of clinical interest for their potential use in regenerative medicine and immunotherapy. Originally derived from bone marrow (BM), MSC have now been isolated from most tissues, including umbilical cord (UC) and UC blood (UCB). If MSC from UC are biologically equivalent to those from BM, they would be attractive as a readily available and non-invasive source for cellular therapies. Methods Sections of UC were separated into vascular and Wharton's jelly (WJ) fractions, which were then digested individually to release MSC that were isolated by plastic adherence in a 10% fetal calf serum (FCS) medium, or a low serum medium designed for multipotent adult progenitor cells (MAPC). The resulting perivascular (PV) and WJ MSC lines were assayed for expression of characteristic markers and differentiation and immunosuppressive properties. Results MSC lines were readily derived from most UC tested. Cells grown in MAPC medium (MM) tended to be smaller and more elongated and expressed more nestin, but did not differ substantially in their growth rate, expression of other markers and differentiation capacity. All UC lines tested were adipogenic but poorly osteogenic, and were equivalent in their ability to suppress T-cell proliferation induced by phytohemagglutinin (PHA), activation beads and allostimulation. Conclusions UC is a convenient, efficient source of MSC that can be expanded under low serum conditions for application on future studies of tissue regeneration and immunosuppression. PMID: 19878060 [PubMed - in process] |
| Airway regeneration: the role of the Clara cell secretory protein and the cells that express it. November 3, 2009 at 7:28 am |
| | Airway regeneration: the role of the Clara cell secretory protein and the cells that express it. Cytotherapy. 2009;11(6):676-87 Authors: Wong AP, Keating A, Waddell TK Abstract Clara cell secretory protein (CCSP) is one of the most abundant proteins in the airway surface fluid, and has many putative functions. Recent advances in the field of stem cells and lung regeneration have identified potentially new roles of CCSP and CCSP-expressing cell populations in airway maintenance, repair and regeneration. This review focuses on the airway regenerative potential of CCSP and the cells that express this protein. The use of this protein or CCSP-expressing cells as an indication of biologic processes that contribute to lung injury or repair is highlighted. PMID: 19878054 [PubMed - in process] |
| Synergistic increase in osteosarcoma cell sensitivity to photodynamic therapy with aminolevulinic acid hexyl ester in the presence of hyperthermia. November 3, 2009 at 7:28 am |
| | Synergistic increase in osteosarcoma cell sensitivity to photodynamic therapy with aminolevulinic acid hexyl ester in the presence of hyperthermia. Photomed Laser Surg. 2009 Oct;27(5):791-7 Authors: Yanase S, Nomura J, Matsumura Y, Watanabe Y, Tagawa T OBJECTIVE: We observed that two osteosarcoma cell lines from the same tumor displayed marked differences in their sensitivities to photodynamic therapy (PDT) with aminolevulinic acid hexyl ester (hALA-PDT). We investigated why these two closely related lines had different hALA-PDT sensitivities and whether the PDT phototoxicity of the less sensitive cell line could be increased by a simultaneous application of hyperthermia (HT). METHODS: Flow cytometry was used to evaluate the intracellular accumulation of protoporphyrin IX (PpIX), a metabolic product of aminolevulinic acid, in two human mandibular osteosarcoma cell lines (HOSM-1 and HOSM-2) treated with HT, hALA-PDT, or hALA-PDT combined with HT (PDT + HT). With hALA-PDT, cells treated with 0.2 mM hALA were irradiated with a light dose of 10-80 J/cm(2) from a near-infrared irradiator. With PDT + HT, the cells were treated as for hALA-PDT except that the temperature was raised to 43.5 degrees C during irradiation. RESULTS: At 6 h after hALA treatment, HOSM-2 cells carried about 1.53-fold more PpIX than HOSM-1 cells. With hALA-PDT, the survival rate for HOSM-1 cells treated with 80 J/cm(2) irradiation was 35.7%, while that for HOSM-2 cells treated with 40-80 J/cm(2) was below 12%. With PDT + HT, the survival rate for HOSM-1 and HOSM-2 cells treated with 80 J/cm(2) irradiation was 14.1% and 10.7%, respectively. CONCLUSION: A combination therapy comprising hALA-PDT + HT treatment may be very useful for the treatment of tumors containing cells that are insensitive to hALA-PDT, such as the HOSM-1 cell line described in this study. PMID: 19878029 [PubMed - in process] |
| Covalent surface modification of a titanium alloy with a phosphorylcholine-containing copolymer for reduced thrombogenicity in cardiovascular devices. November 3, 2009 at 7:28 am |
| | Covalent surface modification of a titanium alloy with a phosphorylcholine-containing copolymer for reduced thrombogenicity in cardiovascular devices. J Biomed Mater Res A. 2009 Oct;91(1):18-28 Authors: Ye SH, Johnson CA, Woolley JR, Snyder TA, Gamble LJ, Wagner WR Our objective was to develop a surface modification strategy for a titanium alloy (TiAl6V4) to provide thromboresistance for surfaces in rigorous blood-contacting cardiovascular applications, such as that found in ventricular assist devices. We hypothesized that this could be accomplished by the covalent attachment of a phospholipid polymer, poly(2-methacryloyloxyethylphosphorylcholine (MPC)-co-methacryl acid) (PMA). TiAl6V4 was H2O plasma treated by radio frequency glow discharge, silanated with 3-aminopropyltriethoxysilane (APS), and ammonia plasma treated to increase surface reactivity. The TiAl6V4 surface was then modified with PMA via a condensation reaction between the amino groups on the TiAl6V4 surface and the carboxyl groups on PMA. The surface composition was verified by X-ray photoelectron spectroscopy, confirming successful modification of the TiAl6V4 surfaces with APS and PMA as evidenced by increased Si and P. Plasma treatments with H2O and ammonia were effective at further increasing the surface reactivity of TiAl6V4 as evidenced by increased surface PMA. The adsorption of ovine fibrinogen onto PMA-modified surfaces was reduced relative to unmodified surfaces, and in vitro ovine blood contact through a rocking test revealed marked reductions in platelet deposition and bulk phase platelet activation relative to unmodified TiAl6V4 and polystyrene controls. The results indicate that the PMA-modification scheme for TiAl6V4 surfaces offers a potential pathway to improve the thromboresistance of the blood-contacting surfaces of cardiovascular devices. PMID: 18683221 [PubMed - indexed for MEDLINE] |
| [The development of plastic surgery : Retrospective view of 80 years of "Der Chirurg" (The Surgeon).] November 3, 2009 at 7:01 am |
| | [The development of plastic surgery : Retrospective view of 80 years of "Der Chirurg" (The Surgeon).] Chirurg. 2009 Nov 1; Authors: Horch RE The often groundbreaking developments of new methods in Plastic Surgery have been published in the journal "Der Chirurg" (The Surgeon) ever since its foundation in 1928, when it was established as a journal dealing with all aspects of surgery and containing many innovations and developments. Historically this is also reflected in the establishment of Plastic Surgery initially as a subspecialty and later on as a specialty within the German Society for Surgery. The interdisciplinary character of modern reconstructive and oncological concepts, not only with other specialties but also within various surgical specialties, raises further challenges and leads to new developments in reconstruction, which will definitely induce an increasing amount of knowledge to the advantage of our patients. Scientific and clinical advances over the last 80 years give rise to the hope that similar success will be attained for reconstruction of traumatic and oncological defects and malformations or disfigurations in the future. Consolidated findings from regenerative medicine and tissue engineering will enrich the daily practice of surgical reconstruction. PMID: 19882333 [PubMed - as supplied by publisher] |
| Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. November 3, 2009 at 7:01 am |
| | Developments in injectable multiphasic biomaterials. The performance of microporous biphasic calcium phosphate granules and hydrogels. J Mater Sci Mater Med. 2009 Nov 1; Authors: Daculsi G, Uzel AP, Weiss P, Goyenvalle E, Aguado E Calcium phosphate bioceramic granules associated with hydrosoluble polymers were developed as bone substitutes for various maxillofacial and orthopaedic applications. These injectable bone substitutes, support and regenerate bone tissue and resorb after implantation. The efficiency of these multiphasic materials is due to the osteogenic and osteoconductive properties of the microporous biphasic calcium phosphate. The associated hydrosoluble polymers are considered as carriers in order to achieve the rheological properties of injectable bone substitutes (IBS). In this study, we used 2 semi synthetic hydrosoluble polymers of polysaccharidic origin. The hydroxy propyl methyl cellulose (HPMC), with and without silane, was combined with microporous BCP granules. The presence of silane induced considerable gelation of the suspension. The 2 IBS used (without gelation, IBS1, with gelation, IBS2) were implanted in critical size femoral epiphysis defects in rabbits. No foreign body reactions were observed in either sample. However, because of the higher density from gelation, cell colonisation followed by bone tissue ingrowth was delayed over time with IBS2 compared to the IBS1 without gelation. The results showed resorption of the BCP granule and bone ingrowth at the expense of both IBS with different kinetics. This study demonstrates that the hydrogel cannot be considered merely as a carrier. The gelation process delayed cell and tissue colonisation by slow degradation of the HPMC Si, compared to the faster release of HPMC with IBS1, in turn inducing faster permeability and spaces for tissue ingrowth between the BCP granules. PMID: 19882306 [PubMed - as supplied by publisher] |
| Preparation of pooled human platelet lysate (pHPL) as an efficient supplement for animal serum-free human stem cell cultures. November 3, 2009 at 7:01 am |
| | Preparation of pooled human platelet lysate (pHPL) as an efficient supplement for animal serum-free human stem cell cultures. J Vis Exp. 2009;(32): Authors: Schallmoser K, Strunk D Platelet derived growth factors have been shown to stimulate cell proliferation efficiently in vivo(1,2) and in vitro. This effect has been reported for mesenchymal stromal cells (MSCs), fibroblasts and endothelial colony-forming cells with platelets activated by thrombin(3-5) or lysed by freeze/thaw cycles(6-14) before the platelet releasate is added to the cell culture medium. The trophic effect of platelet derived growth factors has already been tested in several trials for tissue engineering and regenerative therapy.(1,15-17) Varying efficiency is considered to be at least in part due to individually divergent concentrations of growth factors(18,19) and a current lack of standardized protocols for platelet preparation.(15,16) This protocol presents a practicable procedure to generate a pool of human platelet lysate (pHPL) derived from routinely produced platelet rich plasma (PRP) of forty to fifty single blood donations. By several freeze/thaw cycles the platelet membranes are damaged and growth factors are efficiently released into the plasma. Finally, the platelet fragments are removed by centrifugation to avoid extensive aggregate formation and deplete potential antigens. The implementation of pHPL into standard culture protocols represents a promising tool for further development of cell therapeutics propagated in an animal protein-free system. PMID: 19881465 [PubMed - in process] |
| Legal and ethical aspects of organ donation and transplantation. November 3, 2009 at 7:01 am |
| | Legal and ethical aspects of organ donation and transplantation. Indian J Urol. 2009 Jul;25(3):348-55 Authors: Shroff S The legislation called the Transplantation of Human Organ Act (THO) was passed in India in 1994 to streamline organ donation and transplantation activities. Broadly, the act accepted brain death as a form of death and made the sale of organs a punishable offence. With the acceptance of brain death, it became possible to not only undertake kidney transplantations but also start other solid organ transplants like liver, heart, lungs, and pancreas. Despite the THO legislation, organ commerce and kidney scandals are regularly reported in the Indian media. In most instances, the implementation of the law has been flawed and more often than once its provisions have been abused. Parallel to the living related and unrelated donation program, the deceased donation program has slowly evolved in a few states. In approximately one-third of all liver transplants, the organs have come from the deceased donor program as have all the hearts and pancreas transplants. In these states, a few hospitals along with committed NGOs have kept the momentum of the deceased donor program. The MOHAN Foundation (NGO based in Tamil Nadu and Andhra Pradesh) has facilitated 400 of the 1,300 deceased organ transplants performed in the country over the last 14 years. To overcome organ shortage, developed countries are re-looking at the ethics of unrelated programs and there seems to be a move towards making this an acceptable legal alternative. The supply of deceased donors in these countries has peaked and there has been no further increase over the last few years. India is currently having a deceased donation rate of 0.05 to 0.08 per million population. We need to find a solution on how we can utilize the potentially large pool of trauma-related brain deaths for organ donation. This year in the state of Tamil Nadu, the Government has passed seven special orders. These orders are expected to streamline the activity of deceased donors and help increase their numbers. Recently, on July 30, 2008, the Government brought in a few new amendments as a Gazette with the purpose of putting a stop to organ commerce. The ethics of commerce in organ donation and transplant tourism has been widely criticized by international bodies. The legal and ethical principles that we follow universally with organ donation and transplantation are also important for the future as these may be used to resolve our conflicts related to emerging sciences such as cloning, tissue engineering, and stem cells. PMID: 19881131 [PubMed - in process] |
| [Progress of Research for Osteoarthritis. Tissue engineering therapy for osteoarthritis.] November 3, 2009 at 7:01 am |
| | [Progress of Research for Osteoarthritis. Tissue engineering therapy for osteoarthritis.] Clin Calcium. 2009 Nov;19(11):1621-8 Authors: Hattori K, Ohgushi H To repair articular cartilage defects, transplantation of various tissue or cells have been investigated. In 1994, autologous chondrocyte implantation was introduced by Brittberg et al. and the technology has been widely applied to repair cartilage defects caused by trauma. However, it is hard to be applied for articular cartilage defects in osteoarthritic patients. Recently, several researchers are trying to treat osteoarthritis using tissue-engineering approaches on the basis of stem cells and scaffold. In this paper, we introduce the trend of the approaches for cartilage defects and refer to the possibility for the treatments of osteoarthritic patients. PMID: 19880995 [PubMed - in process] |
| Immune evasion by neocartilage-derived chondrocytes: Implications for biologic repair of joint articular cartilage. November 3, 2009 at 7:01 am |
| | Immune evasion by neocartilage-derived chondrocytes: Implications for biologic repair of joint articular cartilage. Stem Cell Res. 2009 Sep 25; Authors: Adkisson HD, Milliman C, Zhang X, Mauch K, Maziarz RT, Streeter PR Degeneration of joint articular cartilage is a leading cause of disability worldwide, and is due in large part to the fact that adult articular cartilage is unable to undergo effective intrinsic repair. To overcome this barrier, we have developed a tissue engineering strategy which harnesses the superior anabolic activity of juvenile chondrocytes to produce a scaffold-independent, living neocartilage graft. Preclinical studies demonstrate that bioengineered neocartilage survives allogeneic and xenogeneic transplantation, suggesting the utility of universal donor-derived neocartilage for joint repair. However, the mechanism underlying neocartilage transplant tolerance remains poorly understood. We show here that neocartilage-derived chondrocytes are unable to stimulate allogeneic T cells in vitro, and they do not constitutively express cell surface molecules required for induction of T cell immune responses, including major histocompatibility complex (MHC) Class II antigens and costimulatory molecules B7-1 and B7-2. Additionally, chondrocytes suppress, in a contact-dependent manner, the proliferation of activated T cells, with suppression associated with chondrocyte expression of multiple negative regulators of immune responses, including B7 family members (B7-H1, B7-DC, B7-H2, B7-H3, and B7-H4), chondromodulin-I and indoleamine 2,3-dioxygenase. Thus, the survival of transplanted bioengineered neocartilage may depend on both passive and active mechanisms of immune evasion. PMID: 19880363 [PubMed - as supplied by publisher] | | |
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| Treatment of stress urinary incontinence with adipose tissue-derived stem cells. November 3, 2009 at 10:45 am |
| | Treatment of stress urinary incontinence with adipose tissue-derived stem cells. Cytotherapy. 2009 Nov 2; Authors: Lin G, Wang G, Banie L, Ning H, Shindel AW, Fandel TM, Lue TF, Lin CS Abstract Background aims. Effective treatment for stress urinary incontinence (SUI) is lacking. This study investigated whether transplantation of adipose tissue-derived stem cells (ADSC) can treat SUI in a rat model. Methods. Rats were induced to develop SUI by postpartum vaginal balloon dilation and bilateral ovariectomy. ADSC were isolated from the peri-ovary fat, examined for stem cell properties, and labeled with thymidine analog BrdU or EdU. Ten rats received urethral injection of saline as a control. Twelve rats received urethral injection of EdU-labeled ADSC and six rats received intravenous injection of BrdU-labeled ADSC through the tail vein. Four weeks later, urinary voiding function was assessed by conscious cystometry. The rats were then killed and their urethras harvested for tracking of ADSC and quantification of elastin, collagen and smooth muscle contents. Results. Cystometric analysis showed that eight out 10 rats in the control group had abnormal voiding, whereas four of 12 (33.3%) and two of six (33.3%) rats in the urethra-ADSC and tail vein-ADSC groups, respectively, had abnormal voiding. Histologic analysis showed that the ADSC-treated groups had significantly higher elastin content than the control group and, within the ADSC-treated groups, rats with normal voiding pattern also had significantly higher elastin content than rats with voiding dysfunction. ADSC-treated normal-voiding rats had significantly higher smooth muscle content than control or ADSC-treated rats with voiding dysfunction. Conclusions. Transplantation of ADSC via urethral or intravenous injection is effective in the treatment and/or prevention of SUI in a pre-clinical setting. PMID: 19878076 [PubMed - as supplied by publisher] | | | | |
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