Tuesday, November 10, 2009

11/11 TE-RegenMed-StemCell feed

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$1M in Stimulus Funds Awarded to Rice University, Texas Heart® Institute for MRI Tracking of Stem Cells
November 10, 2009 at 7:08 pm


$1M in stimulus funds awarded to Rice, Texas Heart Institute for MRI tracking of stem cells
November 10, 2009 at 5:08 pm


U of M Academic Health Center nets nearly $35 million in federal stimulus grants
November 10, 2009 at 4:06 pm


Iowa State University researcher discovers key to vital DNA, protein interaction
November 10, 2009 at 3:05 pm


OncoVista (OVIT) AdnaGen Test Identifies Cancer Stem Cells in the Bloodstream
November 10, 2009 at 2:05 pm


Vitro to Expand Manufacturing Capacity & amp; Report Increased Product Sales for 2009
November 10, 2009 at 11:05 am


Sigma-Aldrich Enters Distribution Agreement With Stemgent, Inc. to Offer Lentivirus-Based Gene Delivery Products for Regenerative Medicine and Stem Cell Research
November 10, 2009 at 11:05 am


Regen: the industry responsible for cell-based therapies
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 783-785.

Pig induced pluripotent stem cells: a new resource for generating genetically modified pigs
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 787-789.

Business Development
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 797-804.

Research Highlights
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 805-807.

Plasticity of stem cells derived from adult periodontal ligament
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 809-821.

Cardiac stem cell genetic engineering using the αMHC promoter
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 823-833.

Assessing the value of autologous and allogeneic cells for regenerative medicine
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 835-853.

Using stem cells to mend the retina in ocular disease
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 855-864.

Engineering the CNS stem cell microenvironment
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 865-877.

Diverse roles of the vasculature within the neural stem cell niche
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 879-897.

Human embryonic stem cells and genomic instability
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 899-909.

Stem cells and regenerative medicine on the Asian horizon: an economic, industry and social perspective
November 10, 2009 at 9:12 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 911-918.

Of mice and men: skin cells, stem cells and ethical uncertainties
November 10, 2009 at 9:11 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 791-791.

News & Views in ... Regenerative Medicine
November 10, 2009 at 9:11 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 793-795.

Acknowledgements
November 10, 2009 at 9:11 am

Regenerative Medicine , November 2009, Vol. 4, No. 6, Pages 931-931.

International Stem Cell Corporation Announces Strategic Enhancement of its Management Team
November 10, 2009 at 8:04 am


Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.
November 10, 2009 at 6:56 am

Related Articles

Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.

Cytokine Growth Factor Rev. 2009 Nov 6;

Authors: Ripamonti U, Petit JC

'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.

PMID: 19897401 [PubMed - as supplied by publisher]


Tissue, cell and pathway engineering.
November 10, 2009 at 6:56 am

Related Articles

Tissue, cell and pathway engineering.

Curr Opin Biotechnol. 2009 Nov 6;

Authors: Chandran S, Naughton GK

PMID: 19897354 [PubMed - as supplied by publisher]


Multipotent skin-derived precursors: from biology to clinical translation.
November 10, 2009 at 6:56 am

Related Articles

Multipotent skin-derived precursors: from biology to clinical translation.

Curr Opin Biotechnol. 2009 Nov 5;

Authors: Hunt DP, Jahoda C, Chandran S

Skin-derived precursor cells (SKPs) are a novel population of neural crest-related precursor cells that can be isolated from embryonic and adult skin. SKPs are capable of generating neuronal, glial and mesodermal progeny. Fate mapping and microdissection experiments have demonstrated a neural crest origin of SKPs within defined niches in adult skin. The finding that SKP derivatives such as Schwann cells and neuronal cells have in vitro and in vivo function raises the possibility of SKPs being both an experimental and therapeutic resource for disease modelling and regenerative medicine. This review focuses on the increased understanding of the developmental and anatomical origins of SKPs and the biotechnological potential of these cells.

PMID: 19896826 [PubMed - as supplied by publisher]


Engineering organs.
November 10, 2009 at 6:56 am

Related Articles

Engineering organs.

Curr Opin Biotechnol. 2009 Nov 5;

Authors: Atala A

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.

PMID: 19896823 [PubMed - as supplied by publisher]


Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming.
November 10, 2009 at 6:56 am

Related Articles

Small molecules that modulate embryonic stem cell fate and somatic cell reprogramming.

Trends Pharmacol Sci. 2009 Nov 4;

Authors: Li W, Ding S

Recent breakthroughs in stem cell biology, especially the development of induced pluripotent stem cell technique, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Improved understanding of stem cell biology, in addition to better control of stem cell fate, is critical to realize this potential. Small molecules, targeting specific signaling pathways and/or mechanisms, have been shown to be useful chemical tools in manipulating cell fate, state and function. These small molecules are starting to play increasingly important roles in both elucidating the fundamental biology of stem cells and facilitating the development of therapeutic approaches toward regenerative medicine. Such approaches could involve cell replacement therapies using homogenous functional cells produced under chemically defined conditions in vitro and the development of small-molecule drugs that can stimulate patients' endogenous cells to repair and regenerate. Here, we review recent progress in using small molecules to sustain pluripotency, or induce differentiation of embryonic stem cells. We also highlight small molecules that can replace transcription factors and/or enhance efficiency during somatic cell reprogramming.

PMID: 19896224 [PubMed - as supplied by publisher]


Generation of functional gut-like organ from mouse induced pluripotent stem cells.
November 10, 2009 at 6:56 am

Related Articles

Generation of functional gut-like organ from mouse induced pluripotent stem cells.

Biochem Biophys Res Commun. 2009 Nov 3;

Authors: Ueda T, Yamada T, Hokuto D, Koyama F, Kasuda S, Kanehiro H, Nakajima Y

Induced pluripotent stem (iPS) cells have the pluripotency to differentiate into broad spectrum derivatives of all three embryonic germ layers. However, the in vitro organ differentiation potential of iPS cells to organize a complex and functional "organ" has not yet been demonstrated. Here we demonstrate that mouse iPS cells have the ability to organize a gut-like organ with motor function in vitro by a hanging drop culture system. This "induced gut (iGut)" exhibited spontaneous contraction and highly coordinated peristalsis accompanied by a transportation of contents. Ultrastructural analysis identified that the iGut had large lumens surrounded by three distinct layers (epithelium, connective tissue and musculature). Immunoreactivity for c-Kit, a marker of interstitial cells of Cajal (ICCs, enteric pacemaker cells), was observed in the wall of the lumen and formed a distinct and dense network. The neurofilament immunoreactivity was identified to form large ganglion-like structures and dense neuronal networks. The iGut was composed of all the enteric components of three germ layers: epithelial cells (endoderm), smooth muscle cells (mesoderm), ICCs (mesoderm), and enteric neurons (ectoderm). This is the first report to demonstrate the in vitro differentiation potential of iPS cells into particular types of functional "organs." This work not only contributes to understanding the mechanisms of incurable gut disease through disease-specific iPS cells, but also facilitates the clinical application of patient-specific iPS cells for novel therapeutic strategies such as patient-specific "organ" regenerative medicine in the future.

PMID: 19895786 [PubMed - as supplied by publisher]


Identification, Isolation and Characterization of HCN4-Positive Pacemaking Cells Derived from Murine Embryonic Stem Cells during Cardiac Differentiation.
November 10, 2009 at 6:56 am

Related Articles

Identification, Isolation and Characterization of HCN4-Positive Pacemaking Cells Derived from Murine Embryonic Stem Cells during Cardiac Differentiation.

Pacing Clin Electrophysiol. 2009 Nov 5;

Authors: Morikawa K, Bahrudin U, Miake J, Igawa O, Kurata Y, Nakayama Y, Shirayoshi Y, Hisatome I

Background: Development of biological pacemaker is a potential treatment for bradyarrhythmias. Pacemaker cells could be extracted from differentiated embryonic stem (ES) cells based on their specific cell marker hyperpolarization-activated cyclic nucleotide-gated (HCN)4. The goal of this study was to develop a method of identification, isolation, and characterization of pacemaking cells derived from differentiated ES cells with GFP driven by HCN4 promoter. Methods and Results: Polymerase chain reaction (PCR) screening and southern blot analysis revealed that HCN4p-EGFP trans-gene was stably integrated into the chromosome of mouse AB1 ES cells. RT-PCR and immunostaining results showed similar expression of the specific cardiac pacemaker markers of the HCN4p-EGFP ES cells and its parental AB1 ES cell lines. Although HCN4p-EGFP trans-gene may have slight effect on the general mesodermal differentiation, it had no effect on the pluripotency of ES cells, on the transcription of cardiac specific factors and cardiac contractile proteins, and on the capability of ES cells to differentiate into pacemaker cells. Electrophysiological study indicated that HCN4p-GFP-positive cells revealed the spontaneous action potential, which was slowed by the treatment with 2 mM Cs(+), and expressed the hyperpolarization-activeted cation current I(f) encoded by HCN4 gene. Conclusion: By the approach of using stable transfectant of HCN4p-EGFP gene, the identification, isolation, and characterization of ES cell-derived pacemaking cells could be carried out. (PACE 2009; 1-14).

PMID: 19895411 [PubMed - as supplied by publisher]


Recent advances in quantitative chimerism analysis.
November 10, 2009 at 6:56 am

Related Articles

Recent advances in quantitative chimerism analysis.

Expert Rev Mol Diagn. 2009 Nov;9(8):817-32

Authors: Gineikiene E, Stoskus M, Griskevicius L

Quantitative chimerism analysis is a diagnostic tool used to monitor engraftment kinetics after allogeneic stem cell transplantation. It reflects the proportion of recipient and donor genotypes and is based on the identification of genetic markers characteristic to a given transplant pair. Currently, PCR amplification of short tandem repeats and single-nucleotide polymorphism-specific quantitative real-time PCR are the most widely used techniques for this purpose. In this review, we will address advances as well as technology-specific imperfections, of both techniques that have emerged over the recent years. We will discuss new principles that may simplify assay design, and improve its robustness and reliability. A better chimerism assay could then guide clinical interventions and may, eventually, improve the outcome of allogeneic stem cell transplantation.

PMID: 19895227 [PubMed - in process]


In-vivo Assessment of a Tissue-engineered Vascular Graft Combining a Biodegradable Elastomeric Scaffold and Muscle-Derived Stem Cells in a Rat Model.
November 10, 2009 at 6:56 am

Related Articles

In-vivo Assessment of a Tissue-engineered Vascular Graft Combining a Biodegradable Elastomeric Scaffold and Muscle-Derived Stem Cells in a Rat Model.

Tissue Eng Part A. 2009 Nov 6;

Authors: Nieponice A, Soletti L, Guan J, Hong Y, Maul T, Gharaibeh B, Huard J, Wagner W, Vorp D

Limited autologous vascular graft availability and poor patency rates of synthetic grafts for bypass or replacement of small diameter arteries remain a concern in the surgical community. These limitations could potentially be improved by a tissue engineering approach. We report here our progress in the development and in-vivo testing of a stem cell-based tissue engineered vascular graft (TEVG) for arterial applications. Polyester urethane urea scaffolds (length=10mm, ID=1.2mm) were created by thermally induced phase separation (TIPS). Compound scaffolds were generated by reinforcing TIPS scaffolds with an outer electrospun layer of the same biomaterial (ES-TIPS). Both TIPS and ES-TIPS scaffolds were bulk-seeded with 10x106 allogeneic, LacZ transfected, muscle-derived stem cells (MDSCs), then placed in spinner flask culture at for 48 h. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks. Angiograms and histological assessment were performed at the time of explant. Cell-seeded constructs showed a higher patency rate than the unseeded controls: 65% (ES-TIPS) and 53% (TIPS) vs. 10% (acellular TIPS). TIPS scaffolds had a 50% mechanical failure rate with aneurysmal formation while no dilation was observed in the hybrid scaffolds. A smooth muscle-like layer of cells was observed near the luminal surface of the constructs that stained positive for smooth muscle alpha-actin and calponin. LacZ+ cells were shown to be engrafted in the remodeled construct. A confluent layer of vWF-positive cells was observed in the lumen of MDSC-seeded constructs, whereas acellular controls showed platelet and fibrin deposition. This is the first evidence that MDSCs improve patency and contribute to the remodeling of a TEVG for arterial applications.

PMID: 19895206 [PubMed - as supplied by publisher]


Profile of new green fluorescent protein transgenic Jinhua pigs as an imaging source.
November 10, 2009 at 6:56 am

Related Articles

Profile of new green fluorescent protein transgenic Jinhua pigs as an imaging source.

J Biomed Opt. 2009 Sep-Oct;14(5):054017

Authors: Kawarasaki T, Uchiyama K, Hirao A, Azuma S, Otake M, Shibata M, Tsuchiya S, Enosawa S, Takeuchi K, Konno K, Hakamata Y, Yoshino H, Wakai T, Ookawara S, Tanaka H, Kobayashi E, Murakami T

Animal imaging sources have become an indispensable material for biological sciences. Specifically, gene-encoded biological probes serve as stable and high-performance tools to visualize cellular fate in living animals. We use a somatic cell cloning technique to create new green fluorescent protein (GFP)-expressing Jinhua pigs with a miniature body size, and characterized the expression profile in various tissues/organs and ex vivo culture conditions. The born GFP-transgenic pig demonstrate an organ/tissue-dependent expression pattern. Strong GFP expression is observed in the skeletal muscle, pancreas, heart, and kidney. Regarding cellular levels, bone-marrow-derived mesenchymal stromal cells, hepatocytes, and islet cells of the pancreas also show sufficient expression with the unique pattern. Moreover, the cloned pigs demonstrate normal growth and fertility, and the introduced GFP gene is stably transmitted to pigs in subsequent generations. The new GFP-expressing Jinhua pigs may be used as new cellular/tissue light resources for biological imaging in preclinical research fields such as tissue engineering, experimental regenerative medicine, and transplantation.

PMID: 19895119 [PubMed - in process]


Novel Embryoid Body-Based Method to Derive Mesenchymal Stem Cells from Human Embryonic Stem Cells.
November 10, 2009 at 6:43 am

Related Articles

Novel Embryoid Body-Based Method to Derive Mesenchymal Stem Cells from Human Embryonic Stem Cells.

Tissue Eng Part A. 2009 Nov 7;

Authors: Lee EJ, Lee HN, Kang HJ, Kim KH, Hur J, Cho HJ, Lee J, Chung HM, Cho J, Cho MY, Oh SK, Moon SY, Park YB, Kim HS

Application of human embryonic stem cells (hESCs) to stem-cell therapy is not feasible because of the risk of tumorigenicity and rejection. In contrast, human mesenchymal stem cells (hMSCs) are free from the risk of tumorigenicity and also have immune privilege. However, hMSCs obtained from adults have infinite variety in terms of the biological characteristics and functionality. We report here a new derivation method of hMSCs from hESCs. The derivation of hMSCs from three different hESC lines (SNUhES3, CHA3-hESC, and H9) was performed by embryoid bodies formation and subsequent culture with stage-different media without using inductive xenogenic feeder and mechanical selection procedure. The derived cells were morphologically similar to the unique fingerprint-like pattern of hMSCs and grew stably for at least 35 passages in vitro. These cells had hMSCs-like immunophenotypes: negative for CD34 and CD45; positive for CD29, CD44, CD73, CD90, and CD105. They could be differentiated into multiple lineages including osteocytes, chondrocytes, adipocytes, and myocytes. They maintained normal karyotype during the long-term cultivation and did not show tumorigenicity when transplanted into the immunodeficient mice. In conclusion, the new embryoid body-based derivation method of hMSCs from hESCs is simple, safe, and reproducible in three different hESC lines. We expect that this method will provide a more effective and powerful tool to derive hMSCs from various hESC lines.

PMID: 19895342 [PubMed - as supplied by publisher]


Nanoscale engineering of biomimetic surfaces: cues from the extracellular matrix.
November 10, 2009 at 6:26 am

Related Articles

Nanoscale engineering of biomimetic surfaces: cues from the extracellular matrix.

Cell Tissue Res. 2009 Nov 7;

Authors: von der Mark K, Park J, Bauer S, Schmuki P

The ultimate goal in the design of biomimetic materials for use in tissue engineering as permanent or resorbable tissue implants is to generate biocompatible scaffolds with appropriate biomechanical and chemical properties to allow the adhesion, ingrowth, and survival of cells. Recent efforts have therefore focused on the construction and modification of biomimetic surfaces targeted to support tissue-specific cell functions including adhesion, growth, differentiation, motility, and the expression of tissue-specific genes. Four decades of extensive research on the structure and biological influence of the extracellular matrix (ECM) on cell behavior and cell fate have shown that three types of information from the ECM are relevant for the design of biomimetic surfaces: (1) physical properties (elasticity, stiffness, resilience of the cellular environment), (2) specific chemical signals from peptide epitopes contained in a wide variety of extracelluar matrix molecules, and (3) the nanoscale topography of microenvironmental adhesive sites. Initial physical and chemical approaches aimed at improving the adhesiveness of biomaterial surfaces by sandblasting, particle coating, or etching have been supplemented by attempts to increase the bioactivity of biomaterials by coating them with ECM macromolecules, such as fibronectin, elastin, laminin, and collagens, or their integrin-binding epitopes including RGD, YIGSR, and GFOGER. Recently, the development of new nanotechnologies such as photo- or electron-beam nanolithography, polymer demixing, nano-imprinting, compression molding, or the generation of TiO(2) nanotubes of defined diameters (15-200 nm), has opened up the possibility of constructing biomimetic surfaces with a defined nanopattern, eliciting tissue-specific cellular responses by stimulating integrin clustering. This development has provided new input into the design of novel biomaterials. The new technologies allowing the construction of a geometrically defined microenvironment for cells at the nanoscale should facilitate the investigation of nanotopography-dependent mechanisms of integrin-mediated cell signaling.

PMID: 19898872 [PubMed - as supplied by publisher]


Engineering Craniofacial Structures: Facing the Challenge.
November 10, 2009 at 6:26 am

Related Articles

Engineering Craniofacial Structures: Facing the Challenge.

J Dent Res. 2009 Nov 6;

Authors: Zaky SH, Cancedda R

The human innate regenerative ability is known to be limited by the intensity of the insult together with the availability of progenitor cells, which may cause certain irreparable damage. It is only recently that the paradigm of tissue engineering found its way to the treatment of irreversibly affected body structures with the challenge of reconstructing the lost part. In the current review, we underline recent trials that target engineering of human craniofacial structures, mainly bone, cartilage, and teeth. We analyze the applied engineering strategies relative to the selection of cell types to lay down a specific targeted tissue, together with their association with an escorting scaffold for a particular engineered site, and discuss their necessity to be sustained by growth factors. Challenges and expectations for facial skeletal engineering are discussed in the context of future treatment.

PMID: 19897785 [PubMed - as supplied by publisher]


Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.
November 10, 2009 at 6:26 am

Related Articles

Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration.

Cytokine Growth Factor Rev. 2009 Nov 6;

Authors: Ripamonti U, Petit JC

'Bone: Formation by autoinduction', initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-beta (TGF-beta) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-beta isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-beta superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.

PMID: 19897401 [PubMed - as supplied by publisher]


A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture.
November 10, 2009 at 6:26 am

Related Articles

A biomimetic hydrogel based on methacrylated dextran-graft-lysine and gelatin for 3D smooth muscle cell culture.

Biomaterials. 2009 Nov 6;

Authors: Liu Y, Chan-Park MB

Many synthetic hydrogels for cell encapsulation have hitherto been based on polyethylene glycol which is non-natural, non-biodegradable and only terminal-functionalizable, all of which are drawbacks for tissue engineering or cell delivery. The polysaccharide dextran is also highly hydrophilic but biodegradable and pendant-functionalizable and more closely resembles glycosaminoglycans to mimic the natural extracellular matrix. This study reports synthesis of a methacrylate and lysine functionalized dextran and development of hydrogel composite systems based on this material and methacrylamide modified gelatin. The mechanical stiffness and degree of swelling of the hydrogels were varied by manipulation of the degree of functionalization of dextran and gelatin and concentration/composition of precursor solution. Human umbilical artery smooth muscle cells (SMCs) were encapsulated inside hydrogels during gel hardening with photopolymerization. Rapid cell spreading, extensive cellular network formation and high SMC proliferation occurred within softer hydrogels (with shear storage moduli ranging from 898 to 3124Pa). The encapsulated SMCs appear to be relatively contractile in the initial culture than on tissue culture polystyrene dish due to physical constraint imposed by the hydrogels but they become more synthetic with time possibly due to the inability of cells to reach confluence inside these cell-mediated degradable hydrogels. From the impressive cell proliferation and network formation, these new hydrogels combining polysaccharide and protein derivatives appear to be excellent candidates for further development as bioactive scaffolds for use in vascular tissue engineering and regeneration.

PMID: 19897239 [PubMed - as supplied by publisher]


Engineering organs.
November 10, 2009 at 6:26 am

Related Articles

Engineering organs.

Curr Opin Biotechnol. 2009 Nov 5;

Authors: Atala A

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.

PMID: 19896823 [PubMed - as supplied by publisher]


A linearized formulation of triphasic mixture theory for articular cartilage, and its application to indentation analysis.
November 10, 2009 at 6:26 am

Related Articles

A linearized formulation of triphasic mixture theory for articular cartilage, and its application to indentation analysis.

J Biomech. 2009 Nov 5;

Authors: Lu XL, Wan LQ, Edward Guo X, Mow VC

The negative charges on proteoglycans significantly affect the mechanical behaviors of articular cartilage. Mixture theories, such as the triphasic theory, can describe quantitatively how this charged nature contributes to the mechano-electrochemical behaviors of such tissue. However, the mathematical complexity of the theory has hindered its application to complicated loading profiles, e.g., indentation or other multi-dimensional configurations. In this study, the governing equations of triphasic mixture theory for soft tissue were linearized and dramatically simplified by using a regular perturbation method and the use of two potential functions. We showed that this new formulation can be used for any axisymmetric problem, such as confined or unconfined compressions, hydraulic perfusion, and indentation. A finite difference numerical program was further developed to calculate the deformational, electrical, and flow behaviors inside the articular cartilage under indentation. The calculated tissue response was highly consistent with the data from indentation experiments (our own and those reported in the literature). It was found that the charged nature of proteoglycans can increase the apparent stiffness of the solid matrix and lessen the viscous effect introduced by fluid flow. The effects of geometric and physical properties of indenter tip, cartilage thickness, and that of the electro-chemical properties of cartilage on the resulting deformation and fluid pressure fields across the tissue were also investigated and presented. These results have implications for studying chondrocyte mechanotransduction in different cartilage zones and for tissue engineering designs or in vivo cartilage repair.

PMID: 19896670 [PubMed - as supplied by publisher]


Slow freezing cryopreservation of neural stem cell spheres with different diameters.
November 10, 2009 at 6:26 am

Related Articles

Slow freezing cryopreservation of neural stem cell spheres with different diameters.

Cryobiology. 2009 Nov 3;

Authors: Ma XH, Shi Y, Hou Y, Liu Y, Zhang L, Fan WX, Ge D, Liu TQ, Cui ZF

Neural stem cells (NSCs) are of great value for clinical application and scientific research. The development of efficient cryopreservation protocols could significantly facilitate the storage and transportation for clinic applications. The objective of the present study is to improve the survival rate and viability of NSCs. Neural stem cells with three states of single cell suspension, NSC spheres with diameters of 30 approximately 50mum and 80 approximately 100mum, were cryopreserved by slow freezing method with the cryo-pretective agent (CPA) of dimethyl sulfoxide (Me(2)SO), respectively. Then the post-thawing NSCs were tested for the survival rate and the differentiation ability. As a result, NSC spheres with diameter of 80 approximately 100mum and Me(2)SO concentration of 8% achieve the survival rate of 82.9%, and the NSCs still sustain the multi-differentiation potentiality. These results indicated that both the subtle interaction among NSCs and sphere diameters may affect the survival rate together.

PMID: 19895801 [PubMed - as supplied by publisher]


Characterization of biocompatible collagen fibres- A promising candidate for cardiac patch.
November 10, 2009 at 6:26 am

Related Articles

Characterization of biocompatible collagen fibres- A promising candidate for cardiac patch.

Tissue Eng Part C Methods. 2009 Nov 6;

Authors: Srinivasan A, Sehgal PK

Type I and III collagen forms the natural framework of the heart and decellularized heart tissue revealed a fine weave of three dimensionally arranged collagen fibres. In order to mimic this structure for the fabrication of a cardiac patch, a process has been devised to extract solid atelopeptide collagen from bovine tendon while preserving its inherent tensile properties. Unlike chemical/ enzymatic methods, which involve cellular disruption or reconstitution, this microbial collagen extraction process helps to get pure collagen fibres with its native properties intact. There is economy of extraction time hence, enhancement of productivity. The extracted collagen type I and III fibres have a D-periodicity of ~ 67nm as commonly observed for collagen fibrils under Transmission Electron Microscopy (TEM). Mechanical properties such as stress-strain relationship of the fibres were studied and tensile strength was found to be 112.30+/-10.0 MPa. In vitro and in vivo studies reveal that the biocompatible fibres could be woven as a fleece to get a 3 D scaffold with good mechanical strength, not offered by soluble collagen preparations, suitable for tissue engineering applications particularly as a cardiac patch.

PMID: 19895207 [PubMed - as supplied by publisher]


In-vivo Assessment of a Tissue-engineered Vascular Graft Combining a Biodegradable Elastomeric Scaffold and Muscle-Derived Stem Cells in a Rat Model.
November 10, 2009 at 6:26 am

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In-vivo Assessment of a Tissue-engineered Vascular Graft Combining a Biodegradable Elastomeric Scaffold and Muscle-Derived Stem Cells in a Rat Model.

Tissue Eng Part A. 2009 Nov 6;

Authors: Nieponice A, Soletti L, Guan J, Hong Y, Maul T, Gharaibeh B, Huard J, Wagner W, Vorp D

Limited autologous vascular graft availability and poor patency rates of synthetic grafts for bypass or replacement of small diameter arteries remain a concern in the surgical community. These limitations could potentially be improved by a tissue engineering approach. We report here our progress in the development and in-vivo testing of a stem cell-based tissue engineered vascular graft (TEVG) for arterial applications. Polyester urethane urea scaffolds (length=10mm, ID=1.2mm) were created by thermally induced phase separation (TIPS). Compound scaffolds were generated by reinforcing TIPS scaffolds with an outer electrospun layer of the same biomaterial (ES-TIPS). Both TIPS and ES-TIPS scaffolds were bulk-seeded with 10x106 allogeneic, LacZ transfected, muscle-derived stem cells (MDSCs), then placed in spinner flask culture at for 48 h. Constructs were implanted as interposition grafts in the abdominal aorta of rats for 8 weeks. Angiograms and histological assessment were performed at the time of explant. Cell-seeded constructs showed a higher patency rate than the unseeded controls: 65% (ES-TIPS) and 53% (TIPS) vs. 10% (acellular TIPS). TIPS scaffolds had a 50% mechanical failure rate with aneurysmal formation while no dilation was observed in the hybrid scaffolds. A smooth muscle-like layer of cells was observed near the luminal surface of the constructs that stained positive for smooth muscle alpha-actin and calponin. LacZ+ cells were shown to be engrafted in the remodeled construct. A confluent layer of vWF-positive cells was observed in the lumen of MDSC-seeded constructs, whereas acellular controls showed platelet and fibrin deposition. This is the first evidence that MDSCs improve patency and contribute to the remodeling of a TEVG for arterial applications.

PMID: 19895206 [PubMed - as supplied by publisher]

 

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