Monday, November 30, 2009

12/1 TE-RegenMed-StemCell feed

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TE-RegenMed-StemCell feed - By; Ankur Gupta Feed My Inbox

Similarities of pumping blood and oil examined
November 30, 2009 at 2:19 pm


New stem cell technology developed at Hebrew University
November 30, 2009 at 12:19 pm


Kiadis Pharma Announces Enrollment of First Patients in a Multinational Registration Study for ATIR(TM)
November 30, 2009 at 9:18 am

 

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Saturday, November 28, 2009

11/29 TE-RegenMed-StemCell feed

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TE-RegenMed-StemCell feed - By; Ankur Gupta Feed My Inbox

New Figures Show CIRM Spending $1.2 Million-plus for Grant Management
November 28, 2009 at 3:50 pm

In its first-ever public accounting of spending for its grant management system, the California stem cell agency this week disclosed it has already laid out more than $1.2 million, with substantially greater expenditures to come in the near future.Overseeing CIRM's largess is no small task. The agency has approved 320 grants and one loan worth more than $1 billion. It is expected to approve

CIRM Grant Management Info and Costs
November 28, 2009 at 3:32 pm

Here is a rundown on key documents related to CIRM's $1.2 million-plus expenditures on its grant management system.Articles from the California Stem Cell ReportCost Overruns and Candor from CIRM – May 29, 2008Vagueness in CIRM budget, June 2009, with some info on the system:"The budget does not appear to contain a straight-forward accounting of all the past costs associated with the Grantium

Adipose Stem Cells and Skin Repair.
November 28, 2009 at 8:14 am

Adipose Stem Cells and Skin Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Jeong JH

With the discovery of adipose stem cells (ASCs), 40 years after the identification of bone marrow stem cells, a new era of active stem cell therapy has opened. The abundance of stem cells harvested from adipose tissue enables us to instantly apply primary cells without culture expansion. ASCs are already clinically applied in many other purposes such as cell-enriched lipotransfer, wound healing, skin rejuvenation, scar remodeling and skin tissue engineering. Although cellular mechanism of ASCs is not completely understood, recent researches have disclosed some of their unique functions as mesenchymal stem cells. There have been increasing numbers of scientific reports on the therapeutic effect of ASCs on skin repair, scar remodeling and rejuvenation. Wound healing and scar remodeling are complex, multi-cellular processes that involve coordinated efforts of many cell types and various cytokines. Recent reports showed ASCs as a powerful source of skin regeneration because of their capability to provide not only cellular elements, but also numerous cytokines. Currently, other attractive functions of ASCs in the recovery of extrinsic aging and radiation damage are under active investigation. It seems that autologous ASCs have great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions. This review will focus on the specific roles of ASCs in skin tissue, especially related with wound healing, radiation injury, scar remodeling, skin rejuvenation and skin engineering.

PMID: 19941454 [PubMed - as supplied by publisher]


Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine.
November 28, 2009 at 6:38 am

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Salgado AJ, Reis RL, Sousa N, Gimble JM

Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose- derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing simultaneously higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.

PMID: 19941460 [PubMed - as supplied by publisher]


Adipose Tissue Regeneration.
November 28, 2009 at 6:38 am

Adipose Tissue Regeneration.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Brayfield CA, Marra KG, Rubin JP

The repair of soft tissue defects, particularly after trauma and oncologic surgery, represents a major clinical challenge. While current reconstructive procedures can move soft tissue from other areas of the body, there remains an unmet need for new modalities that are less invasive and more precise. Adipose tissue is the key component necessary for soft tissue reconstruction. This review will discuss the discovery and potential of adult stem therapies in the regeneration of adipose tissue. Adipose-derived stem cells (ASCs), are being examined as cell delivery systems for soft tissue reconstruction. In addition to a further understanding of the biology of ASCs, appropriate biomaterials (e.g., cell delivery vehicles), rapid expansion of stem cells using bioreactors, and suitable animal models for adipose tissue engineering are needed for successful stem cell therapies, and will be discussed in this review. Clinical studies with ASCs are being conducted in Europe and Asia and will be described.

PMID: 19941458 [PubMed - as supplied by publisher]


Cartilage Regeneration Using Adipose-Derived Stem Cells.
November 28, 2009 at 6:38 am

Cartilage Regeneration Using Adipose-Derived Stem Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Ogawa R, Mizuno S

The first tissue engineering product, autologous chondrocytes implantation or transplantation (ACI or ACT), has been available for over a decade. Recently, adult tissue-derived stem cells have received great interest for their ability to promote tissue regeneration. To date, adipose-derived stem cells (ASCs) have been evaluated for new surgical procedures to reconstruct damaged and defective tissue, because they are easiest to harvest due to the large number of stem cells compared to other stem cell sources. However, there are issues in using ASCs for cartilage repair. Thus, we need more information regarding optimal culture conditions and methods to promote chondrogenic lineages of stem cells. The necessary information includes necessary differentiation factors, cell scaffolds, and cell culture conditions. We reviewed the methodology for manufacturing cell constructs using ASCs for clinical applications.

PMID: 19941456 [PubMed - as supplied by publisher]


The Potential for Treatment of Skeletal Muscle Disorders with Adipose-Derived Stem Cells.
November 28, 2009 at 6:38 am

The Potential for Treatment of Skeletal Muscle Disorders with Adipose-Derived Stem Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Mizuno H

Stem cell based therapies for the repair and regeneration of various tissues and organs offer a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. This review focuses on skeletal muscle regeneration and repair by adipose-derived stem cells (ASCs) with particular attention to their potential use as a therapy for disorders such as degenerative muscle diseases or skeletal muscle injuries. ASCs can differentiate into skeletal muscle cells in vitro either in co-culture with skeletal myoblasts, or when cultured in medium supplemented with horse serum and/or under reduced serum conditions. In particular, spontaneous fusion of ASCs and subsequent myotube-like formation was observed in early culture passages at high cell density. ASCs have also shown a capacity for myogenic differentiation in vivo. In a murine muscular dystrophy model, ASCs were able to restore muscle function following direct injection into the affected muscle as well as following intravenous systemic administration. Of great importance is the finding that allogeneic ASCs injected into the damaged muscle were not rejected, even without immunosuppressive therapy. Because human adipose tissue is ubiquitous and easily obtainable in large quantities under local anesthesia with little patient discomfort, it presents an appealing source of stem cells for mesenchymal tissue regeneration and engineering.

PMID: 19941455 [PubMed - as supplied by publisher]


Adipose Stem Cells and Skin Repair.
November 28, 2009 at 6:38 am

Adipose Stem Cells and Skin Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Jeong JH

With the discovery of adipose stem cells (ASCs), 40 years after the identification of bone marrow stem cells, a new era of active stem cell therapy has opened. The abundance of stem cells harvested from adipose tissue enables us to instantly apply primary cells without culture expansion. ASCs are already clinically applied in many other purposes such as cell-enriched lipotransfer, wound healing, skin rejuvenation, scar remodeling and skin tissue engineering. Although cellular mechanism of ASCs is not completely understood, recent researches have disclosed some of their unique functions as mesenchymal stem cells. There have been increasing numbers of scientific reports on the therapeutic effect of ASCs on skin repair, scar remodeling and rejuvenation. Wound healing and scar remodeling are complex, multi-cellular processes that involve coordinated efforts of many cell types and various cytokines. Recent reports showed ASCs as a powerful source of skin regeneration because of their capability to provide not only cellular elements, but also numerous cytokines. Currently, other attractive functions of ASCs in the recovery of extrinsic aging and radiation damage are under active investigation. It seems that autologous ASCs have great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions. This review will focus on the specific roles of ASCs in skin tissue, especially related with wound healing, radiation injury, scar remodeling, skin rejuvenation and skin engineering.

PMID: 19941454 [PubMed - as supplied by publisher]


Aesthetic Cardiology: Adipose-Derived Stem Cells for Myocardial Repair.
November 28, 2009 at 6:38 am

Aesthetic Cardiology: Adipose-Derived Stem Cells for Myocardial Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Palpant NJ, Metzger JM

Stem cell biology has increasingly gained scientific and public interest in recent years. In particular, the use of stem cells for treatment of heart disease has been strongly pursued within the scientific and medical communities. Significant effort has gone into the use of adult tissue-derived stem cells for cardiac repair including bone marrow, blood, and cardiac-derived cell populations. Significant interest in this area has been balanced by the difficulties of understanding stem cells, cardiac injury, and the amalgamation of these areas of investigation in translational medicine. Recent studies have emerged on adipose-derived stem cells which show the potential for cardiac lineage development in vitro and may have application in cell-mediated in vivo therapy for the diseased heart. This review provides a summary of current findings within the field of adipose-derived stem cell biology regarding their cardiac differentiation potential.

PMID: 19941452 [PubMed - as supplied by publisher]


Perspectives on Adipose-Derived Stem/Stromal Cells as Potential Treatment for Scarred Vocal Folds: Opportunity and Challenges.
November 28, 2009 at 6:38 am

Perspectives on Adipose-Derived Stem/Stromal Cells as Potential Treatment for Scarred Vocal Folds: Opportunity and Challenges.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Kumai Y, Kobler JB, Herrera VL, Zeitels SM

Regenerative therapy using stem cells for the treatment of vocal fold wound healing and fibrosis is a very active area of research in Otolaryngology. Although modern phonosurgical methods can deal with many types of vocal fold pathology, vocal fold scar remains a clinical challenge. Trauma (e.g. vocal abuse, phonosurgery) and inflammation (e.g. laryngitis) are the two main causes of the vocal fold scarring. Several recent reviews detail the problem of vocal fold scarring and the array of possible solutions under investigation. The search for solutions includes autologous tissues, biomaterial implants, growth factors, anti-fibrotic agents and stem cells. This review focuses on emerging research on stem cells for vocal fold regeneration and our own studies of interactions between adipose-derived stem/stromal cells and vocal fold fibroblasts using an in vitro model. While clearly an opportunity, the challenging approach of treating vocal scarring using ASCs has just started. For future in vivo studies, improvements in cell viability and markers of stem-cell differentiation into normal fibroblasts are needed. The roles of stem cell-derived cytokines in paracrine signaling need to be further explored at a cellular level in vitro, and then extended to in vivo experiments.

PMID: 19941448 [PubMed - as supplied by publisher]


Adipose Tissue Derived Stem Cells for Regeneration and Differentiation into Insulin-Producing Cells.
November 28, 2009 at 6:38 am

Adipose Tissue Derived Stem Cells for Regeneration and Differentiation into Insulin-Producing Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Kim SC, Han DJ, Lee JY

Stem cells are considered an ideal tool for the supply of insulin-producing cells or repairing damaged pancreatic tissues to treat diabetes mellitus, with the possibility of unlimited sources. This cell population includes embryonic, adult bone marrow, pancreatic stem cells, extra pancreatic (such as hepatic cells) and adipose-derived stem cells. Multipotent adipose tissue-derived stem cells (ADSCs) are abundant in the human body, and thus are an ideal donor source for autologous transplantation to generate insulin-producing cells. Moreover these cells are better sources than bone marrow stem cells (BMSCs) for clinical applications, owing to minimal invasive procedures, high proliferation and multi-differentiation potential. Human adipose tissue-derived stem cells (hADSCs) may thus provide an alternative stem cell source, replacing BM-MSCs or embryonic stem cells (ESCs) for future clinical use in diabetes mellitus treatment.

PMID: 19941446 [PubMed - as supplied by publisher]


Cornea and Ocular Surface Treatment.
November 28, 2009 at 6:38 am

Cornea and Ocular Surface Treatment.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: De Miguel MP, Alio JL, Arnalich-Montiel F, Fuentes-Julian S, de Benito-Llopis L, Amparo F, Bataille L

In addition to being a protective shield, the cornea represents two thirds of the eye's refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach.

PMID: 19941445 [PubMed - as supplied by publisher]


In vitro cytokeratin expression profiling of human oral mucosa substitutes developed by tissue engineering.
November 28, 2009 at 6:24 am

In vitro cytokeratin expression profiling of human oral mucosa substitutes developed by tissue engineering.

Int J Artif Organs. 2009 Nov 26;32(10):711-719

Authors: Garzon I, Serrato D, Roda O, Del Carmen Sanchez-Quevedo M, Gonzales-Jaranay M, Moreu G, Nieto-Aguilar R, Alaminos M, Campos A

In this work we performed a study of cytokeratin (CK) expression profiling on human artificial oral mucosa developed in vitro by tissue engineering at different stages of maturation (from immature to well-developed stages) at the protein and mRNA levels. Human artificial oral mucosa was generated in the laboratory using fibrin-agarose biomaterials. As controls, we used human native normal oral mucosa and embryonic oral tissues. Our results demonstrated that human embryonic oral tissues tended to express CK8 and CK19. In contrast, monolayered bioengineered oral mucosa did not show any CK expression by immunohistochemistry, whereas bilayered and multilayered artificial oral mucosa showed several markers of stratified epithelia, but did not express CK10. These results suggest that the CK expression pattern is strongly dependent on the maturation state of the artificial tissues and that the CK expression profile of our model of artificial oral mucosa was partially similar to that of the non-keratinized human adult oral mucosa. However, the expression of CK8 by the artificial oral mucosa suggests that these samples correspond to an early stage of development while kept in vitro.

PMID: 19943232 [PubMed - as supplied by publisher]


Pulmonary tissue engineering using dual-compartment polymer scaffolds with integrated vascular tree.
November 28, 2009 at 6:24 am

Pulmonary tissue engineering using dual-compartment polymer scaffolds with integrated vascular tree.

Int J Artif Organs. 2009 Nov 26;32(10):701-710

Authors: Fritsche CS, Simsch O, Weinberg EJ, Orrick B, Stamm C, Kaazempur-Mofrad MR, Borenstein JT, Hetzer R, Vacanti JP

Objectives: The persistent shortage of donor organs for lung transplantation illustrates the need for new strategies in organ replacement therapy. Pulmonary tissue engineering aims at developing viable hybrid tissue for patients with chronic respiratory failure. Methods: Dual-chamber polymer constructs that mimic the characteristics of the pulmonary air-blood interface were fabricated by microfabrication techniques using the biocompatible polymer polydimethylsiloxane. One compartment ("vascular chamber") was designed as a capillary network to mimic the pulmonary microvasculature. The other compartment ("parenchymal chamber") was designed to permit gas exchange. Immortalized mouse lung epithelium cells (MLE-12) were cultured on the surface of polystyrene microcarrier beads. These beads were subsequently injected into the parenchymal chamber of the dual-chamber microsystems. The vascular compartment was perfused with cell culture medium in a bioreactor and the construct was maintained in culture for 1 week. Results: The microcarriers evenly distributed MLE-12 cells on the parenchymal compartment surface. Confluent cell layers were confirmed by fluorescent and electron microscopy. Adequate proliferation of MLE-12 cells within the construct was monitored via the DNA content. Viability of the cells was maintained over 1 week. Finally, cellular specificity and functional capacity in situ were demonstrated by immunostaining for proSP-B and proSP-C (alveolar epithelium), and by using MLE-12 cells transfected to overexpress green fluorescent protein. Conclusion: We conclude that functional hybrid microsystems mimicking the basic building plan of alveolar tissue can be engineered in vitro.

PMID: 19943231 [PubMed - as supplied by publisher]


In vitro construction of scaffold-free cylindrical cartilage using cell sheet-based tissue engineering.
November 28, 2009 at 6:24 am

In vitro construction of scaffold-free cylindrical cartilage using cell sheet-based tissue engineering.

Pediatr Surg Int. 2009 Nov 27;

Authors: Tani G, Usui N, Kamiyama M, Oue T, Fukuzawa M

PURPOSE: Tissue-engineered cartilage may offer a solution for the treatment of serious airway disease. This study developed a novel procedure to fabricate a scaffold-free cylindrical cartilage under in vitro conditions, while also evaluating the effect of a dynamic culture on the engineered construct. METHODS: Auricular chondrocytes were harvested from New Zealand white rabbits and cultivated under high-density conditions to form a chondrocyte sheet. The sheet was looped around a silicon tube and cultivated for 6 weeks in dynamic or static conditions. The engineered cylindrical cartilages were evaluated macroscopically and histologically. The expression of collagen, glycosaminoglycan content and mechanical properties were determined. RESULTS: The cylindrical cartilage was sufficiently elastic and stiff to maintain the structure without disruption. Histologically, the construct contained a Safranin-O positive cartilaginous matrix accompanied by the expression of type II collagen. The glycosaminoglycan content increased and reached 72% of the native tracheal cartilage after 6 weeks of cultivation. CONCLUSION: A novel procedure was developed for fabricating engineered cartilage, which maintained the shape and a proper level of rigidity and flexibility, under in vitro conditions using sheet-based tissue engineering techniques. This procedure may allow for the development of a tailor-made autograft and a functionally engineered trachea.

PMID: 19943052 [PubMed - as supplied by publisher]


Genetically engineered angiogenic cell sheets using magnetic force-based gene delivery and tissue fabrication techniques.
November 28, 2009 at 6:24 am

Genetically engineered angiogenic cell sheets using magnetic force-based gene delivery and tissue fabrication techniques.

Biomaterials. 2009 Nov 24;

Authors: Akiyama H, Ito A, Kawabe Y, Kamihira M

A major limitation in tissue engineering is the insufficient formation of blood vessels in implanted tissues, resulting in reduced cell density and graft size. We report here the fabrication of angiogenic cell sheets using a combination of two magnetic force-based techniques which use magnetite cationic liposomes (MCLs), magnetofection and magnetic cell accumulation. A retroviral vector encoding an expression cassette of vascular endothelial growth factor (VEGF) was labeled with MCLs, to magnetically attract the particles onto a monolayer of mouse myoblast C2C12 cells, for gene delivery. MCL-mediated infection increased transduction efficiency by 6.7-fold compared with the conventional method. During the fabrication of the tissue constructs, MCL-labeled cells were accumulated in the presence of a magnetic field to promote the spontaneous formation of a multilayered cell sheet. VEGF gene-engineered C2C12 (C2C12/VEGF) cell sheets, constructed using both magnetic force-based techniques, were subcutaneously transplanted into nude mice. Histological analyses revealed that on day 14 the C2C12/VEGF cell sheet grafts had produced thick tissues, with a high-cell density, and promoted vascularization. This suggests that the method described here represents a powerful strategy in tissue engineering.

PMID: 19942286 [PubMed - as supplied by publisher]


Hard tissue-forming potential of stem/progenitor cells in human dental follicle and dental papilla.
November 28, 2009 at 6:24 am

Hard tissue-forming potential of stem/progenitor cells in human dental follicle and dental papilla.

Arch Oral Biol. 2009 Nov 24;

Authors: Yagyuu T, Ikeda E, Ohgushi H, Tadokoro M, Hirose M, Maeda M, Inagake K, Kirita T

OBJECTIVE: The existence of stem/progenitor cells in dental tissue has been suggested but their characterization in the human tooth germ remains elusive. The purpose of this study was to investigate these cells in human dental follicles and dental papillae at the crown-forming stage and compare their potential for hard tissue formation. DESIGN: We used dental follicle cells (DFCs) and dental papilla cells (DPCs) derived from dental follicles and dental papillae at the crown-forming stage and compared their proliferative capacity, cell surface antigens and ability to form hard tissue in vitro and in vivo. RESULTS: Both DFCs and DPCs had extensive proliferation ability, expressed similar cell surface antigens and were capable of forming hard tissue in vivo as well as in vitro. However, there were two differences between DFCs and DPCs. First, DPCs had a significantly higher calcium accumulation than that in DFCs. Second, DFCs expressed a cementoblast marker, whereas DPCs expressed an odontoblast marker. CONCLUSIONS: We propose that dental follicles and dental papillae at the crown-forming stage contain different types of stem/progenitor cells and may have hard tissue-forming ability in a possibly origin-specific lineage direction.

PMID: 19942210 [PubMed - as supplied by publisher]


Mechanical and swelling characterization of P(NIPAAm-co-mPEGMA) sol-gels.
November 28, 2009 at 6:24 am

Mechanical and swelling characterization of P(NIPAAm-co-mPEGMA) sol-gels.

Acta Biomater. 2009 Nov 23;

Authors: Pollock JF, Healy KE

The dimensional stability and rheological properties of a series of comb-like copolymers of N-isopropyl acrylamide and methoxy poly(ethylene glycol) methacrylate, P(NIPAAm-co-mPEGMA), with varying PEG graft density and molecular weight were studied. The thermoresponsive character of the copolymer solutions was investigated by kinetic and equilibrium swelling, as well as by static and dynamic mechanical analysis. Surface response mapping was employed to target particular compositions and concentrations with excellent dimensional stability and relatively large change in dynamic mechanical properties upon thermoreversible gelation. The mechanical characteristics of the gels depended strongly upon concentration of total polymer and less so upon copolymer ratio. Increased PEG graft density was shown to slow the deswelling rate and increase the equilibrium water content of the gels. Upon gelation at sol concentrations of 1 wt% to 20 wt%, the materials underwent no deswelling or syneresis and maintained stable gels with a large elastic regime and high yield strain (i.e. elastic and soft but tough), even within the pascal range of complex shear moduli. These materials are unique in that they maintained a physiologically useful lower critical solution temperature ( approximately 33 (o)C), despite having a high PEG content. Copolymers with high PEG content and low polymer fraction were conveniently transparent in the gel phase, allowing visualization of cellular activity without disrupting the microenvironment. Mesenchymal stem cells showed good viability and proliferation in 3D culture within the gels, despite the lack of ligand incorporation to promote cellular interaction. Multi-component matrices can be created through simple mixing of copolymer solutions and peptide-conjugated linear polymers and proteins to produce combinatorial microenvironments with potential for use in cell biology, tissue engineering, and medical applications.

PMID: 19941981 [PubMed - as supplied by publisher]


Design and Evaluation of Novel Polyanhydride Blends as Nerve Guidance Conduits.
November 28, 2009 at 6:24 am

Design and Evaluation of Novel Polyanhydride Blends as Nerve Guidance Conduits.

Acta Biomater. 2009 Nov 23;

Authors: Griffin J, Carbone A, Delgado-Rivera R, Meiners S, Uhrich KE

Implantable biodegradable nerve guidance conduits (NGCs) have the potential to align and support regenerating cells, as well as prevent scar formation. In this study, in vitro bioassays and in vivo material evaluation is performed using a nerve guidance conduit material from a novel polyanhydride blend. In vitro cytotoxicity studies with both fibroblast and primary chick neurons demonstrated that the proposed polyanhydride blend is noncytotoxic. Subcutaneous implantation for seven days in rats resulted in an initial fibrin matrix, minimal macrophage presence, and angiogenesis in the surrounding tissues. Nerve guidance conduits fabricated from the proposed polyanhydride blend material may serve as favorable biocompatible tissue engineering devices.

PMID: 19941978 [PubMed - as supplied by publisher]


Stem cell-mediated natural tissue engineering.
November 28, 2009 at 6:24 am

Stem cell-mediated natural tissue engineering.

J Cell Mol Med. 2009 Nov 21;

Authors: Möllmann H, Nef HM, Voss S, Troidl C, Willmer M, Szardien S, Rolf A, Klement M, Voswinckel R, Kostin S, Ghofrani HA, Hamm CW, Elsässer A

ABSTRACT Background-Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct-related septum rupture. We hypothesized that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. Methods and Results-We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after prespecified intervals of 3 days, and 2, 6, and 12 weeks; the newly developed tissue was evaluated using quantitative RT-PCR, immunohistochemistry, and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with GM-CSF early after implantation. We demonstrated the time-dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells, and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM-CSF led to more rapid tissue growth and differentiation. The GM-CSF effect on cell proliferation outlasted the treatment period by several weeks. Conclusions-Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.

PMID: 19941631 [PubMed - as supplied by publisher]


Adipose Tissue Regeneration.
November 28, 2009 at 6:24 am

Adipose Tissue Regeneration.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Brayfield CA, Marra KG, Rubin JP

The repair of soft tissue defects, particularly after trauma and oncologic surgery, represents a major clinical challenge. While current reconstructive procedures can move soft tissue from other areas of the body, there remains an unmet need for new modalities that are less invasive and more precise. Adipose tissue is the key component necessary for soft tissue reconstruction. This review will discuss the discovery and potential of adult stem therapies in the regeneration of adipose tissue. Adipose-derived stem cells (ASCs), are being examined as cell delivery systems for soft tissue reconstruction. In addition to a further understanding of the biology of ASCs, appropriate biomaterials (e.g., cell delivery vehicles), rapid expansion of stem cells using bioreactors, and suitable animal models for adipose tissue engineering are needed for successful stem cell therapies, and will be discussed in this review. Clinical studies with ASCs are being conducted in Europe and Asia and will be described.

PMID: 19941458 [PubMed - as supplied by publisher]


Bone Regeneration and Repair.
November 28, 2009 at 6:24 am

Bone Regeneration and Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Panetta NJ, Gupta DM, Longaker MT

In the face of mounting clinical demand, and armed with reconstructive techniques that are technically challenging and frequently result in suboptimal patient outcomes, increasing focus is being placed on tissue engineering and regenerative medicine as a potential source of novel skeletal reconstructive approaches. Specifically, evidence is accumulating that highlights the promise of osteoprogenitor cell-based reconstructive strategies to meet the needs of an expanding patient population. Historically, the study of cell and molecular biology guiding physiologic and pathologic skeletal development, as well as endogenous bone regeneration following injury, has provided a wealth of information that lends insight toward potential parallel processes that may regulate the osteogenic differentiation of progenitor cells. Multiple progenitor cell populations are now known to possess a capacity to undergo robust osteogenic differentiation in the presence of appropriate environmental cues (hESC, BMSC, ASC, etc.) Recent investigations have put forth multiple advantages of ASC relative to BMSC. Of note, ASC exist in relative abundance, lack the need for in vitro expansion prior to utilization, and can be harvested with relative ease and reduced donor morbidity. Collectively, these factors, paired with promising in vitro and in vivo observations that speak toward the substantial osteogenic potential of ASC, have spurred enthusiasm to pursue the application of ASC in the maturation of skeletal tissue engineering applications. Yet, elucidating what structural and functional properties of scaffolds designed for ASC-mediated skeletal tissue engineering applications (porosity, pore size, composition, mechanical stability, degradation kinetics, etc.), as well as evolving our understanding and capacity to deliver spatiotemporally specific pro-osteogenic targeted molecular manipulation to progenitor cells, remain important hurdles to clear. The scope of this review encompasses the current state of ongoing investigations along these fronts, as well as what future direction will be critical to the transition of cell-based skeletal tissue engineering strategies to the bedside.

PMID: 19941457 [PubMed - as supplied by publisher]

 

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11/29 RegenMD

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New Figures Show CIRM Spending $1.2 Million-plus for Grant Management
November 28, 2009 at 7:50 am


CIRM Grant Management Info and Costs
November 28, 2009 at 7:32 am

 

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11/29 pubmed: adipose stem cell

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Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine.
November 28, 2009 at 9:29 am

Adipose Tissue Derived Stem Cells Secretome: Soluble Factors and Their Roles in Regenerative Medicine.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Salgado AJ, Reis RL, Sousa N, Gimble JM

Stem cells have been long looked at as possible therapeutic vehicles for different health related problems. Among the different existing stem cell populations, Adipose- derived Stem Cells (ASCs) have been gathering attention in the last 10 years. When compared to other stem cells populations and sources, ASCs can be easily isolated while providing simultaneously higher yields upon the processing of adipose tissue. Similar to other stem cell populations, it was initially thought that the main potential of ASCs for regenerative medicine approaches was intimately related to their differentiation capability. Although this is true, there has been an increasing body of literature describing the trophic effects of ASCs on the protection, survival and differentiation of variety of endogenous cells/tissues. Moreover, they have also shown to possess an immunomodulatory character. This effect is closely related to the ASCs' secretome and the soluble factors found within it. Molecules such as hepatocyte growth factor (HGF), granulocyte and macrophage colony stimulating factors, interleukins (ILs) 6, 7, 8 and 11, tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), adipokines and others have been identified within the ASCs' secretome. Due to its importance regarding future applications for the field of regenerative medicine, we aim, in the present review, to make a comprehensive analysis of the literature relating to the ASCs' secretome and its relevance to the immune and central nervous system, vascularization and cardiac regeneration. The concluding section will highlight some of the major challenges that remain before ASCs can be used for future clinical applications.

PMID: 19941460 [PubMed - as supplied by publisher]


Adipose Tissue Regeneration.
November 28, 2009 at 9:29 am

Adipose Tissue Regeneration.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Brayfield CA, Marra KG, Rubin JP

The repair of soft tissue defects, particularly after trauma and oncologic surgery, represents a major clinical challenge. While current reconstructive procedures can move soft tissue from other areas of the body, there remains an unmet need for new modalities that are less invasive and more precise. Adipose tissue is the key component necessary for soft tissue reconstruction. This review will discuss the discovery and potential of adult stem therapies in the regeneration of adipose tissue. Adipose-derived stem cells (ASCs), are being examined as cell delivery systems for soft tissue reconstruction. In addition to a further understanding of the biology of ASCs, appropriate biomaterials (e.g., cell delivery vehicles), rapid expansion of stem cells using bioreactors, and suitable animal models for adipose tissue engineering are needed for successful stem cell therapies, and will be discussed in this review. Clinical studies with ASCs are being conducted in Europe and Asia and will be described.

PMID: 19941458 [PubMed - as supplied by publisher]


Cartilage Regeneration Using Adipose-Derived Stem Cells.
November 28, 2009 at 9:29 am

Cartilage Regeneration Using Adipose-Derived Stem Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Ogawa R, Mizuno S

The first tissue engineering product, autologous chondrocytes implantation or transplantation (ACI or ACT), has been available for over a decade. Recently, adult tissue-derived stem cells have received great interest for their ability to promote tissue regeneration. To date, adipose-derived stem cells (ASCs) have been evaluated for new surgical procedures to reconstruct damaged and defective tissue, because they are easiest to harvest due to the large number of stem cells compared to other stem cell sources. However, there are issues in using ASCs for cartilage repair. Thus, we need more information regarding optimal culture conditions and methods to promote chondrogenic lineages of stem cells. The necessary information includes necessary differentiation factors, cell scaffolds, and cell culture conditions. We reviewed the methodology for manufacturing cell constructs using ASCs for clinical applications.

PMID: 19941456 [PubMed - as supplied by publisher]


The Potential for Treatment of Skeletal Muscle Disorders with Adipose-Derived Stem Cells.
November 28, 2009 at 9:29 am

The Potential for Treatment of Skeletal Muscle Disorders with Adipose-Derived Stem Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Mizuno H

Stem cell based therapies for the repair and regeneration of various tissues and organs offer a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. This review focuses on skeletal muscle regeneration and repair by adipose-derived stem cells (ASCs) with particular attention to their potential use as a therapy for disorders such as degenerative muscle diseases or skeletal muscle injuries. ASCs can differentiate into skeletal muscle cells in vitro either in co-culture with skeletal myoblasts, or when cultured in medium supplemented with horse serum and/or under reduced serum conditions. In particular, spontaneous fusion of ASCs and subsequent myotube-like formation was observed in early culture passages at high cell density. ASCs have also shown a capacity for myogenic differentiation in vivo. In a murine muscular dystrophy model, ASCs were able to restore muscle function following direct injection into the affected muscle as well as following intravenous systemic administration. Of great importance is the finding that allogeneic ASCs injected into the damaged muscle were not rejected, even without immunosuppressive therapy. Because human adipose tissue is ubiquitous and easily obtainable in large quantities under local anesthesia with little patient discomfort, it presents an appealing source of stem cells for mesenchymal tissue regeneration and engineering.

PMID: 19941455 [PubMed - as supplied by publisher]


Adipose Stem Cells and Skin Repair.
November 28, 2009 at 9:29 am

Adipose Stem Cells and Skin Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Jeong JH

With the discovery of adipose stem cells (ASCs), 40 years after the identification of bone marrow stem cells, a new era of active stem cell therapy has opened. The abundance of stem cells harvested from adipose tissue enables us to instantly apply primary cells without culture expansion. ASCs are already clinically applied in many other purposes such as cell-enriched lipotransfer, wound healing, skin rejuvenation, scar remodeling and skin tissue engineering. Although cellular mechanism of ASCs is not completely understood, recent researches have disclosed some of their unique functions as mesenchymal stem cells. There have been increasing numbers of scientific reports on the therapeutic effect of ASCs on skin repair, scar remodeling and rejuvenation. Wound healing and scar remodeling are complex, multi-cellular processes that involve coordinated efforts of many cell types and various cytokines. Recent reports showed ASCs as a powerful source of skin regeneration because of their capability to provide not only cellular elements, but also numerous cytokines. Currently, other attractive functions of ASCs in the recovery of extrinsic aging and radiation damage are under active investigation. It seems that autologous ASCs have great promise for applications in repair of skin, rejuvenation of aging skin and aging-related skin lesions. This review will focus on the specific roles of ASCs in skin tissue, especially related with wound healing, radiation injury, scar remodeling, skin rejuvenation and skin engineering.

PMID: 19941454 [PubMed - as supplied by publisher]


Aesthetic Cardiology: Adipose-Derived Stem Cells for Myocardial Repair.
November 28, 2009 at 9:29 am

Aesthetic Cardiology: Adipose-Derived Stem Cells for Myocardial Repair.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Palpant NJ, Metzger JM

Stem cell biology has increasingly gained scientific and public interest in recent years. In particular, the use of stem cells for treatment of heart disease has been strongly pursued within the scientific and medical communities. Significant effort has gone into the use of adult tissue-derived stem cells for cardiac repair including bone marrow, blood, and cardiac-derived cell populations. Significant interest in this area has been balanced by the difficulties of understanding stem cells, cardiac injury, and the amalgamation of these areas of investigation in translational medicine. Recent studies have emerged on adipose-derived stem cells which show the potential for cardiac lineage development in vitro and may have application in cell-mediated in vivo therapy for the diseased heart. This review provides a summary of current findings within the field of adipose-derived stem cell biology regarding their cardiac differentiation potential.

PMID: 19941452 [PubMed - as supplied by publisher]


Perspectives on Adipose-Derived Stem/Stromal Cells as Potential Treatment for Scarred Vocal Folds: Opportunity and Challenges.
November 28, 2009 at 9:29 am

Perspectives on Adipose-Derived Stem/Stromal Cells as Potential Treatment for Scarred Vocal Folds: Opportunity and Challenges.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Kumai Y, Kobler JB, Herrera VL, Zeitels SM

Regenerative therapy using stem cells for the treatment of vocal fold wound healing and fibrosis is a very active area of research in Otolaryngology. Although modern phonosurgical methods can deal with many types of vocal fold pathology, vocal fold scar remains a clinical challenge. Trauma (e.g. vocal abuse, phonosurgery) and inflammation (e.g. laryngitis) are the two main causes of the vocal fold scarring. Several recent reviews detail the problem of vocal fold scarring and the array of possible solutions under investigation. The search for solutions includes autologous tissues, biomaterial implants, growth factors, anti-fibrotic agents and stem cells. This review focuses on emerging research on stem cells for vocal fold regeneration and our own studies of interactions between adipose-derived stem/stromal cells and vocal fold fibroblasts using an in vitro model. While clearly an opportunity, the challenging approach of treating vocal scarring using ASCs has just started. For future in vivo studies, improvements in cell viability and markers of stem-cell differentiation into normal fibroblasts are needed. The roles of stem cell-derived cytokines in paracrine signaling need to be further explored at a cellular level in vitro, and then extended to in vivo experiments.

PMID: 19941448 [PubMed - as supplied by publisher]


Adipose Tissue Derived Stem Cells for Regeneration and Differentiation into Insulin-Producing Cells.
November 28, 2009 at 9:29 am

Adipose Tissue Derived Stem Cells for Regeneration and Differentiation into Insulin-Producing Cells.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: Kim SC, Han DJ, Lee JY

Stem cells are considered an ideal tool for the supply of insulin-producing cells or repairing damaged pancreatic tissues to treat diabetes mellitus, with the possibility of unlimited sources. This cell population includes embryonic, adult bone marrow, pancreatic stem cells, extra pancreatic (such as hepatic cells) and adipose-derived stem cells. Multipotent adipose tissue-derived stem cells (ADSCs) are abundant in the human body, and thus are an ideal donor source for autologous transplantation to generate insulin-producing cells. Moreover these cells are better sources than bone marrow stem cells (BMSCs) for clinical applications, owing to minimal invasive procedures, high proliferation and multi-differentiation potential. Human adipose tissue-derived stem cells (hADSCs) may thus provide an alternative stem cell source, replacing BM-MSCs or embryonic stem cells (ESCs) for future clinical use in diabetes mellitus treatment.

PMID: 19941446 [PubMed - as supplied by publisher]


Cornea and Ocular Surface Treatment.
November 28, 2009 at 9:29 am

Cornea and Ocular Surface Treatment.

Curr Stem Cell Res Ther. 2009 Nov 26;

Authors: De Miguel MP, Alio JL, Arnalich-Montiel F, Fuentes-Julian S, de Benito-Llopis L, Amparo F, Bataille L

In addition to being a protective shield, the cornea represents two thirds of the eye's refractive power. Corneal pathology can affect one or all of the corneal layers, producing corneal opacity. Although full corneal thickness keratoplasty has been the standard procedure, the ideal strategy would be to replace only the damaged layer. Current difficulties in corneal transplantation, mainly immune rejection and shortage of organ supply, place more emphasis on the development of artificial corneas. Bioengineered corneas range from prosthetic devices that solely address the replacement of the corneal function, to tissue-engineered hydrogels that allow regeneration of the tissue. Recently, major advances in the biology of corneal stem cells have been achieved. However, the therapeutic use of these stem cell types has the disadvantage of needing an intact stem cell compartment, which is usually damaged. In addition, long ex vivo culture is needed to generate enough cell numbers for transplantation. In the near future, combination of advanced biomaterials with cells from abundant outer sources will allow advances in the field. For the former, magnetically aligned collagen is one of the most promising ones. For the latter, different cell types will be optimal: 1) for epithelial replacement: oral mucosal epithelium, ear epidermis, or bone marrow- mesenchymal stem cells, 2) for stromal regeneration: adipose-derived stem cells and 3) for endothelial replacement, the possibility of in vitro directed differentiation of adipose-derived stem cells towards endothelial cells provides an exciting new approach.

PMID: 19941445 [PubMed - as supplied by publisher]

 

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