| CIRM Approves $300,000 More for Tech Help, Including Grant Management
December 3, 2009 at 8:51 pm
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| | The Governance Subcommittee of the California stem cell agency yesterday approved spending an additional $300,000 for technology assistance as it wrestles with its $1.2 million – and growing – grants management system.A $100,000 increase was okayed for Turner Consulting Group of Washington, D.C., and a $200,000 extension for 25by7 of Santa Monica, Ca., according to a CIRM spokesman. Turner began |
| UCSB, UCL scientists rescue visual function in rats using induced pluripotent stem cells
December 3, 2009 at 4:33 pm
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| StemCells, Inc. Welcomes Approval of First Embryonic Stem Cell Lines Under New NIH Guidelines
December 3, 2009 at 1:15 pm
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| Gladstone scientists identify strategies to protect new brain cells against Alzheimer's disease
December 3, 2009 at 1:15 pm
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| Beike Biotechnology CSO Speaks on Role of Stem Cells in Treating Diabetic Foot Disease at IPA Diabetic Foot Care Conference, India
December 3, 2009 at 11:13 am
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| Allos Therapeutics to Launch Global Registry for Patients with Peripheral T-Cell Lymphoma at the American Society of Hematology Annual Meeting
December 3, 2009 at 9:13 am
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| Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge.
December 3, 2009 at 8:50 am
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| | Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge. Ear Hear. 2009 Nov 25; Authors: McCall AA, Swan EE, Borenstein JT, Sewell WF, Kujawa SG, McKenna MJ Delivery of medications to the inner ear has been an area of considerable growth in both the research and clinical realms during the past several decades. Systemic delivery of medication destined for treatment of the inner ear is the foundation on which newer delivery techniques have been developed. Because of systemic side effects, investigators and clinicians have begun developing and using techniques to deliver therapeutic agents locally. Alongside the now commonplace use of intratympanic gentamicin for Meniere's disease and the emerging use of intratympanic steroids for sudden sensorineural hearing loss, novel technologies, such as hydrogels and nanoparticles, are being explored. At the horizon of inner ear drug-delivery techniques, intracochlear devices that leverage recent advances in microsystems technology are being developed to apply medications directly into the inner ear. Potential uses for such devices include neurotrophic factor and steroid delivery with cochlear implantation, RNA interference technologies, and stem-cell therapy. The historical, current, and future delivery techniques and uses of drug delivery for treatment of inner ear disease serve as the basis for this review. PMID: 19952751 [PubMed - as supplied by publisher] |
| On-demand three-dimensional freeform fabrication of multi-layered hydrogel scaffold with fluidic channels.
December 3, 2009 at 6:54 am
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| | On-demand three-dimensional freeform fabrication of multi-layered hydrogel scaffold with fluidic channels. Biotechnol Bioeng. 2009 Dec 1; Authors: Lee W, Lee V, Polio S, Keegan P, Lee JH, Fischer K, Park JK, Yoo SS One of the challenges in tissue engineering is to provide adequate supplies of oxygen and nutrients to cells within the engineered tissue construct. Soft-lithographic techniques have allowed the generation of hydrogel scaffolds containing a network of fluidic channels, but at the cost of complicated and often time-consuming manufacturing steps. We report a three-dimensional (3D) direct printing technique to construct hydrogel scaffolds containing fluidic channels. Cells can also be printed on to and embedded in the scaffold with this technique. Collagen hydrogel precursor was printed and subsequently crosslinked via nebulized sodium bicarbonate solution. A heated gelatin solution, which served as a sacrificial element for the fluidic channels, was printed between the collagen layers. The process was repeated layer-by-layer to form a 3D hydrogel block. The printed hydrogel block was heated to 37 degrees C, which allowed the gelatin to be selectively liquefied and drained, generating a hollow channel within the collagen scaffold. The dermal fibroblasts grown in a scaffold containing fluidic channels showed significantly elevated cell viability compared to the ones without any channels. The on-demand capability to print fluidic channel structures and cells in a 3D hydrogel scaffold offers flexibility in generating perfusable 3D artificial tissue composites. (c) 2009 Wiley Periodicals, Inc. PMID: 19953677 [PubMed - as supplied by publisher] |
| Effect of Buguzhi (Psoralea corylifolia fruit) extract on bone formation.
December 3, 2009 at 6:54 am
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| | Effect of Buguzhi (Psoralea corylifolia fruit) extract on bone formation. Phytother Res. 2009 Dec 1; Authors: Wong RW, Rabie AB The objective of the study is to compare the amount of new bone produced by Buguzhi (Psoralea corylifolia fruit) extract in collagen matrix to that produced and collagen matrix in vivo. Eighteen bone defects, 5 mm by 10 mm, were created in the parietal bone of 9 New Zealand white rabbits. Six defects were grafted with Buguzhi extract mixed with collagen matrix. Six defects were grafted with collagen matrix alone (positive control) and 6 were left empty (negative control). Animals were sacrificed on day 14 and the defects were dissected and prepared for histological assessment. Quantitative analysis of new bone formation and bone cells was made on 100 sections (50 sections for each group) using image analysis. A total of 275% more new bone was present in defects grafted with Buguzhi extract in collagen matrix than those grafted with collagen matrix. No bone was formed in the negative control group. The amount of bone cells was also significantly greater in the Buguzhi group than in the positive control group. To conclude, Buguzhi extract in collagen matrix has the effect of increasing new bone formation locally in vivo. Buguzhi extract in collagen matrix can be used as a bone graft material. Copyright (c) 2009 John Wiley & Sons, Ltd. PMID: 19953524 [PubMed - as supplied by publisher] |
| Flexor Tendon Tissue Engineering: Temporal Distribution of Donor Tenocytes versus Recipient Cells.
December 3, 2009 at 6:54 am
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| | Flexor Tendon Tissue Engineering: Temporal Distribution of Donor Tenocytes versus Recipient Cells. Plast Reconstr Surg. 2009 Dec;124(6):2019-26 Authors: Thorfinn J, Saber S, Angelidis IK, Ki SH, Zhang AY, Chong AK, Pham HM, Lee GK, Chang J BACKGROUND:: Tissue-engineered tendon material may address tendon shortages in mutilating hand injuries. Tenocytes from rabbit flexor tendon can be successfully seeded onto acellularized tendons that are used as tendon constructs. These constructs in vivo exhibit a population of tenocyte-like cells; however, it is not known to what extent these cells are of donor or recipient origin. Furthermore, the temporal distribution is also not known. METHODS:: Tenocytes from New Zealand male rabbits were cultured and seeded onto acellularized rabbit forepaw flexor tendons (n = 48). These tendon constructs were transplanted into female recipients. Tendons were examined after 3, 6, 12, and 30 weeks using fluorescent in situ hybridization to detect the Y chromosome in the male donor cells. One unseeded, acellularized allograft in each animal was used as a control. RESULTS:: The donor male tenocytes populate the epitenon and endotenon of the grafts at greater numbers than the recipient female tenocytes at 3 and 6 weeks. The donor and recipient tenocytes are present jointly in the grafts until 12 weeks. At 30 weeks, nearly all cells are recipient tenocyte-like cells. CONCLUSIONS:: Donor male cells survive in decreasing numbers over time until 30 weeks. The presence of cells in tissue-engineered tendon grafts has been shown in prior studies to add to the strength of the constructs in vitro. This study shows that recipient cells can migrate into and repopulate the tendon construct. Cell seeding onto tendon material may create stronger constructs that will allow the initiation of motion earlier. PMID: 19952658 [PubMed - in process] |
| Human and mouse osteoprogenitor cells exhibit distinct patterns of osteogenesis in three-dimensional tissue engineering scaffolds.
December 3, 2009 at 6:54 am
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| | Human and mouse osteoprogenitor cells exhibit distinct patterns of osteogenesis in three-dimensional tissue engineering scaffolds. Plast Reconstr Surg. 2009 Dec;124(6):1869-79 Authors: Pereira CT, Huang W, Jarrahy R, Rudkin G, Yamaguchi DT, Miller TA BACKGROUND:: Understanding interspecies variation between animal models and humans is essential to develop tissue-engineered bone. The authors studied osteogenic and angiogenic marker expression in human and murine osteoblasts and mesenchymal stem cells. METHODS:: Three human cells (human mesenchymal stem cells, multilineage progenitor cells, and normal human osteoblasts) and three murine cells (MC3T3-E1, C3H10T1/2, and M2-10B4) were used. Cells were seeded onto poly-lactide-glycolic acid-coated tissue culture plates or three-dimensional poly-lactide-glycolic acid scaffolds, incubated in osteogenic medium, and harvested at 1, 4, and 7 days. mRNA expression was analyzed using quantitative real-time reverse-transcriptase polymerase chain reaction for osteogenic markers, including alkaline phosphatase, osteocalcin, bone sialoprotein, and core-binding factor alpha-1, and angiogenic markers, including vascular endothelial growth factor and interleukin-8. Data were analyzed using analysis of variance. RESULTS:: All human cells had significantly increased expression of osteogenic markers in three dimensions compared with two dimensions (alkaline phosphatase by 220 percent, osteocalcin by 323 percent, bone sialoprotein by 534 percent, and core-binding factor alpha-1 by 357 percent). However, all murine cells exhibited significant decreases in the expression of osteogenic markers in three-dimensional compared with two-dimensional cultures (alkaline phosphatase by 89 percent, osteocalcin by 64 percent, bone sialoprotein by 76 percent, and core-binding factor alpha-1 by 73 percent). In contrast, all human and murine cells showed markedly elevated expression of angiogenic factors interleukin-8 and vascular endothelial growth factor in three-dimensional compared with two-dimensional cultures. Measurement of alkaline phosphatase activity confirmed this pattern of osteogenic differentiation. CONCLUSIONS:: In three-dimensional versus two-dimensional cultures, osteogenesis increased significantly in human cells but decreased in murine cells; angiogenesis increased regardless of species. Since three-dimensional cultures represent in vivo conditions more closely, this species variation has important translational implications to tissue-engineered bone research. PMID: 19952643 [PubMed - in process] |
| Skin permeation and transdermal delivery systems of drugs: history to overcome barrier function in the stratum corneum.
December 3, 2009 at 6:54 am
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| | Skin permeation and transdermal delivery systems of drugs: history to overcome barrier function in the stratum corneum. Yakugaku Zasshi. 2009 Dec;129(12):1453-8 Authors: Sugino M, Todo H, Sugibayashi K Transdermal Drug Delivery Systems (TDDS), where active drugs must be absorbed into the systemic circulation after penetrating the skin barrier, were first launched in 1979, and about 10 TDDS containing different kinds of drugs were developed during the initial decade. Interestingly, a developmental rush has come again in the present century. Various penetration-enhancing approaches to improve drug permeation of the skin (stratum corneum) have been attempted. These approaches are of two types: chemical and physical. Examples of the chemical approach are enhancers such as alcohol, monoterpenes and fatty acid esters, as well as chemical modification of prodrugs. In contrast, physical approaches include the use of electrical-, thermal- and mechanical-energy, as well as microneedles, needle-free injectors or electroporation to completely or partially evade the barrier function in the stratum corneum. The chemical approaches are mainly effective in increasing the skin permeation of low-molecular chemicals, whereas physical means are effective for these chemicals but also high-molecules like peptides, proteins and nucleotides (DNA or RNA). Marked development has been observed in these physical means in the past decade. In addition, recent developments in tissue engineering technologies enables the use of cultured skin containing keratinocytes and fibroblasts as a TDDS. An effective "cell delivery system" may be a reality in the near future. This paper will look back on the 30-year history of TDDS and evaluate the feasibility of a new generation of these systems. PMID: 19952520 [PubMed - in process] |
| Mending the failing heart with a vascularized cardiac patch.
December 3, 2009 at 6:54 am
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| | Mending the failing heart with a vascularized cardiac patch. Cell Stem Cell. 2009 Dec 4;5(6):575-6 Authors: Hanjaya-Putra D, Gerecht S Functional, stem-cell-containing cardiac grafts will require vascularized myocardial constructs to support their survival and integration into the host vasculature. Recently in Tissue Engineering, Part A, Lesman et al. (2009) reported the successful integration of vascular cells and hESC-derived cardiomyoctyes into stable grafts in rat recipients. PMID: 19951684 [PubMed - in process] |
| A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering.
December 3, 2009 at 6:54 am
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| | A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Ambrose WM, Schein O, Elisseeff J Laboratory investigations of stems cells in regenerative medicine have generated considerable interest within recent years, however some of this excitement is yet to be matched in the clinical arena. Two fields that are well poised to make significant clinical impact in the coming years are those of cartilage and corneal regeneration. In the case of cornea, it is widely acknowledged that corneal epithelium is derived from an adult stem cell type resident within the cornea. These cells, known as limbal stem cells (LSC's), have been widely investigated for their ex-vivo culture and subsequent transplantation efficacy, with some techniques already enjoying limited clinical application. Thus far however, only preliminary evidence currently exists to suggest that there is a population of adult stem cells which gives rise to stromal keratocytes or to the corneal endothelium. A handful of reports have discussed studies in which non-LSC adult stem cells such as mesenchymal stems cells (MSCs) or embryonic stem cells (ESCs) are being applied to corneal regeneration. Though adult stem cells have been shown to exist in articular cartilage, they have proven elusive, which corroborates the limited ability of this tissue to self-repair. Rather, MSCs, ESCs as well as adipose-derived, periosteum-derived, muscle-derived and synovium-derived stem cells (ADCs, PDCs, MDCs and SDCs respectively) are being extensively explored for cartilage regeneration. This review discusses emerging trends in the applications of both adult and embryonic stem cells to cartilage and corneal regeneration, with an emphasis on those techniques that have been applied clinically or which show significant potential for clinical translation. PMID: 19951256 [PubMed - as supplied by publisher] |
| Multilineage potential of Bone Marrow Derived Mesenchymal Stem Cell Cell-Sheets: Implications for Tissue Engineering.
December 3, 2009 at 6:54 am
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| | Multilineage potential of Bone Marrow Derived Mesenchymal Stem Cell Cell-Sheets: Implications for Tissue Engineering. Tissue Eng Part A. 2009 Dec 1; Authors: See EY, Toh SL, Goh JC Bone marrow derived Mesenchymal Stromal Cells (BMSC) is a promising source of cells for tissue engineering due to their multilineage mesenchymal differentiation potential. Their ability to proliferate and differentiate into the osteogenic, chondrogenic and adipogenic lineage make them an attractive cell source as compared to the terminally differentiated cells. In tissue engineering, use of cell-sheet technology is gaining popularity. It is based on culturing cells until hyperconfluence and it has resulted in the reduction of the number of cells lost when seeding onto scaffolds. Thus, formation of cell-sheets with multipotent cells, such as BMSC would be a promising alternative to the conventional method of cell seeding, ie single-cell suspension. However, the multilineage potential of BMSC cell-sheets has yet to be verified. Therefore, the aim of this study was to characterize the formation of a hyperconfluent BMSC cell-sheet as well as the effects of the hyperconfluent culture conditions on the multipotentiality of BMSC. Our results showed that the BMSC cell-sheets remain viable. The cell-sheets were rich with type I collagen and were shown to have retained their multipotentiality. Hence, the use BMSC cell-sheets for tissue engineering application seem promising. PMID: 19951089 [PubMed - as supplied by publisher] |
| A Cascade Biodegradable Polymer Based on Alternating Cyclization and Elimination Reactions.
December 3, 2009 at 6:54 am
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| | A Cascade Biodegradable Polymer Based on Alternating Cyclization and Elimination Reactions. J Am Chem Soc. 2009 Dec 1; Authors: Dewit MA, Gillies ER Polymers that depolymerize by a cascade of intramolecular reactions in response to the removal of a stabilizing end-cap can allow for an unprecedented degree of control over the polymer degradation process. Described here is the development of polymers comprising N,N'-dimethylethylenediamine and 4-hydroxybenzyl alcohol linked by carbamate linkages. The polycarbamate backbone is stable in aqueous solution, but removal of a protective end-cap from the amine terminus allows the diamine to cyclize, forming N,N'-dimethylimidazolidinone and releasing the phenol, which undergoes a 1,6-elimination followed by the release of CO(2) to reveal the next amine to continue the cascade. These polymers therefore degrade by alternating cyclization and elimination reactions. First, a tert-butylcarbamate (Boc) group was introduced as a cleavable end-cap, and the degradation kinetics and mechanism were studied by (1)H nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography. Next, to demonstrate the degradability of these polymers under biologically relevant conditions, poly(ethylene oxide) was introduced as an end-cap via an ester linkage, to provide an amphiphilic block copolymer. This copolymer was found to assemble into cascade degradable nanoparticles that were capable of encapsulating and subsequently releasing a fluorescent dye in aqueous solution. This new class of polymers therefore provides highly promising materials that can be used for the development of medical devices, drug delivery vehicles, and tissue engineering scaffolds with unique biodegradation properties. PMID: 19950931 [PubMed - as supplied by publisher] |
| A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering.
December 3, 2009 at 6:12 am
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| | A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Ambrose WM, Schein O, Elisseeff J Laboratory investigations of stems cells in regenerative medicine have generated considerable interest within recent years, however some of this excitement is yet to be matched in the clinical arena. Two fields that are well poised to make significant clinical impact in the coming years are those of cartilage and corneal regeneration. In the case of cornea, it is widely acknowledged that corneal epithelium is derived from an adult stem cell type resident within the cornea. These cells, known as limbal stem cells (LSC's), have been widely investigated for their ex-vivo culture and subsequent transplantation efficacy, with some techniques already enjoying limited clinical application. Thus far however, only preliminary evidence currently exists to suggest that there is a population of adult stem cells which gives rise to stromal keratocytes or to the corneal endothelium. A handful of reports have discussed studies in which non-LSC adult stem cells such as mesenchymal stems cells (MSCs) or embryonic stem cells (ESCs) are being applied to corneal regeneration. Though adult stem cells have been shown to exist in articular cartilage, they have proven elusive, which corroborates the limited ability of this tissue to self-repair. Rather, MSCs, ESCs as well as adipose-derived, periosteum-derived, muscle-derived and synovium-derived stem cells (ADCs, PDCs, MDCs and SDCs respectively) are being extensively explored for cartilage regeneration. This review discusses emerging trends in the applications of both adult and embryonic stem cells to cartilage and corneal regeneration, with an emphasis on those techniques that have been applied clinically or which show significant potential for clinical translation. PMID: 19951256 [PubMed - as supplied by publisher] |
| Inflammatory biomarkers in combat wound healing.
December 3, 2009 at 6:11 am
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| | Inflammatory biomarkers in combat wound healing. Ann Surg. 2009 Dec;250(6):1002-7 Authors: Hawksworth JS, Stojadinovic A, Gage FA, Tadaki DK, Perdue PW, Forsberg J, Davis TA, Dunne JR, Denobile JW, Brown TS, Elster EA BACKGROUND: Modern war ballistics and blast injuries inflict devastating extremity injuries, violating soft tissue, bone, and neurovascular structures. Despite advances in complex wound management, appropriate timing of war wound closure remains subjective. In addition, the pathophysiology of acute wound failure is poorly defined. METHODS: Patients with penetrating extremity wounds sustained during combat were prospectively studied and followed for 30 days after definitive wound closure. The primary outcome was wound healing. Wound dehiscence was defined as spontaneous partial or complete wound disruption after closure. Serum, wound effluent, and wound bed tissue biopsy were collected at each surgical wound debridement. Serum and wound effluent were analyzed with a multiplex array of 22 cytokines and chemokines, and wound tissue for corresponding gene transcript expression. RESULTS: Fifty-two penetrating extremity war wounds in 33 male patients were investigated. Nine (17%) wounds dehisced. Concomitant vascular injury, increased wound size, and higher injury severity score correlated with wound dehiscence. Both serum and wound effluent cytokine and chemokine protein profiles were statistically associated with healing outcome at various time points. Wound biopsy gene transcript expression demonstrated increased tissue inflammation associated with wound failure. Multiple protein and gene transcript biomarkers predictive of wound healing were identified. CONCLUSIONS: The cytokine and chemokine protein and gene transcript expression patterns demonstrate a condition of inflammatory dysregulation associated with war wound failure. A molecular biomarker panel may predict combat wound healing outcome and warrants prospective validation. PMID: 19953718 [PubMed - in process] |
| Regulating MCP-1 Diffusion in Affinity Hydrogels for Enhancing Immuno-isolation.
December 3, 2009 at 6:11 am
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| | Regulating MCP-1 Diffusion in Affinity Hydrogels for Enhancing Immuno-isolation. J Control Release. 2009 Nov 28; Authors: Lin CC, Boyer PD, Aimetti AA, Anseth KS Delivering cells using semi-permeable hydrogels is becoming an increasingly important direction in cell based therapies and regenerative medicine applications. Synthetic hydrogels have been functionalized with bioactive motifs to render otherwise inert polymer networks responsive. However, little effort has been focused on creating immuno-isolating materials capable of retarding the transport of small antigenic molecules secreted from the cells delivered with the synthetic carriers. Toward the goal of developing a complete immuno-isolation polymeric barrier, affinity peptide-functionalized PEG hydrogels were developed with the ability to sequester monocyte chemotactic protein 1 (MCP-1), a chemokine known to induce the chemotaxis of monocytes, dendritic cells, and memory T-cells. Affinity peptides capable of sequestering MCP-1 were identified from CCR2 (a G protein-coupled receptor for MCP-1) and incorporated within PEG hydrogels via a thiol-acrylate photopolymerization. The release of encapsulated recombinant MCP-1 from PEG hydrogels is readily tuned by: (1) incorporating affinity peptides within the network; and/or (2) altering the spacer distance between the affinity peptide and the crosslinking site. Furthermore, when pancreatic beta-cells were encapsulated within these novel peptide-functionalized hydrogels, the release of cell-secreted MCP-1 was significantly reduced, demonstrating the potential of this new gel formulation to reduce the host innate immune response to transplanted cells by decreasing the recruitment and activation of host monocytes and other immune cells. PMID: 19951731 [PubMed - as supplied by publisher] |
| [Proangiogenic cell-based therapy for treatment of ischemic diseases.]
December 3, 2009 at 6:11 am
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| | [Proangiogenic cell-based therapy for treatment of ischemic diseases.] Med Sci (Paris). 2009 Nov;25(11):931-8 Authors: Silvestre JS The application of endothelial progenitor cells (EPC) cell-based therapy for regenerative medicine constitutes a promising therapeutic avenue for the treatment of cardiovascular diseases. Based on experimental studies demonstrating that bone marrow-, blood- or tissue-derived stem/progenitor cells improve the functional recovery after ischemia, clinical trials were initiated to address this new therapeutic concept. Although autolougous cell therapy was shown to improve perfusion and function of ischemic tissues, a number of issues remain to be adressed. The nature of the mobilizing, migratory and homing signals, and the mechanisms of action need to be identified and further defined. In addition, strategies to enhance homing, survival and therapeutic potential of EPC need to be developped to improve therapeutic effect and counteract EPC dysfunction in aged patients with cardiovascular risk factors. The present review article will discuss the mechanisms of action of different types of adult stem cells and several approaches to improve their therapeutic efficiency. PMID: 19951667 [PubMed - in process] |
| A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering.
December 3, 2009 at 6:11 am
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| | A Tale of Two Tissues: Stem Cells in Cartilage and Corneal Tissue Engineering. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Ambrose WM, Schein O, Elisseeff J Laboratory investigations of stems cells in regenerative medicine have generated considerable interest within recent years, however some of this excitement is yet to be matched in the clinical arena. Two fields that are well poised to make significant clinical impact in the coming years are those of cartilage and corneal regeneration. In the case of cornea, it is widely acknowledged that corneal epithelium is derived from an adult stem cell type resident within the cornea. These cells, known as limbal stem cells (LSC's), have been widely investigated for their ex-vivo culture and subsequent transplantation efficacy, with some techniques already enjoying limited clinical application. Thus far however, only preliminary evidence currently exists to suggest that there is a population of adult stem cells which gives rise to stromal keratocytes or to the corneal endothelium. A handful of reports have discussed studies in which non-LSC adult stem cells such as mesenchymal stems cells (MSCs) or embryonic stem cells (ESCs) are being applied to corneal regeneration. Though adult stem cells have been shown to exist in articular cartilage, they have proven elusive, which corroborates the limited ability of this tissue to self-repair. Rather, MSCs, ESCs as well as adipose-derived, periosteum-derived, muscle-derived and synovium-derived stem cells (ADCs, PDCs, MDCs and SDCs respectively) are being extensively explored for cartilage regeneration. This review discusses emerging trends in the applications of both adult and embryonic stem cells to cartilage and corneal regeneration, with an emphasis on those techniques that have been applied clinically or which show significant potential for clinical translation. PMID: 19951256 [PubMed - as supplied by publisher] |
| Rho Kinase Inhibitor Y27632 Alters the Balance Between Pluripotency and Early Differentiation Events in Human Embryonic Stem Cells.
December 3, 2009 at 6:11 am
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| | Rho Kinase Inhibitor Y27632 Alters the Balance Between Pluripotency and Early Differentiation Events in Human Embryonic Stem Cells. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Sivasubramaniyan K, Pal R, Totey S, Bhat VS, Totey S Human embryonic stem cells (hESC) differentiate spontaneously in culture and develop a complex microenvironment comprising of autologously derived niche that in turn supports their pluripotency. The basic hypothesis that we deal with is that hESCs undergoing differentiation, sequentially generate trophectoderm and endoderm lineages and thereafter influence further events through the production of growth factors. These factors control the fate of hESCs either by promoting or retarding the recruitment of new cells in the differentiation program. This scenario therefore represents an analog of the in vivo situation in which extra-embryonic tissues influence the behavior of the inner cell mass (ICM). The premise of the paper is the Rho kinase inhibitor Y27632 that can spatiotemporally alter this balance between pluripotency and differentiation. To evaluate the composition and inclination of lineage specification during spontaneous differentiation, we have studied the hESC colonies and their surrounding niche as interdependent entities. We show that the population of fibroblastic niche that surrounds hESC colonies co-expresses trophectoderm and niche cell markers including SSEA1, hCG, progesterone, HAND1, pSmad1 and FGFR1 as early as day 4. A sudden increase in the expression of GATA4 and AFP secretion indicated putative endoderm formation on day 6 in both control and Y27632 treated cultures. On day 6, 20 microM of Y27632 supplementation significantly reduced the trophectoderm-like niche population without affecting endoderm formation, enhanced the average size and number of hESC colonies, decreased IGF1 secretion thereby improving the pluripotency. Overall our findings support the afore mentioned hypothesis and demonstrate that closely packed epithelial trophectoderm-like cells bordering the hESC colonies present an initial and imminent localized niche which is spatiotemporally regulated. Such advances in understanding the behavior and modulation of hESC and its surrounding niche would facilitate better differentiation protocols for applications in regenerative medicine and drug screening. PMID: 19951253 [PubMed - as supplied by publisher] |
| Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique.
December 3, 2009 at 6:11 am
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| | Safety and Complications Reporting on the Re-implantation of Culture-Expanded Mesenchymal Stem Cells using Autologous Platelet Lysate Technique. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Centeno CJ, Schultz JR, Cheever M, Robinson B, Freeman M, Marasco W Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the complication rate for autologous MSC therapy is only now beginning to be reported. Methods: Between 2005 and 2009, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=45; group 2: n=182). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints (n=213) or into intervertebral discs (n=13) with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. Results: Mean follow-up from the time of the re-implant procedure was 10.6 +/- 7.3 months. Serial MRI's at 3 months, 6 months, 1 year and 2 years failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented 7 cases of probable procedure-related complications (thought to be associated with the re-implant procedure itself) and three cases of possible stem cell complications, all of which were either self-limited or were remedied with simple therapeutic measures. One patient was diagnosed with cancer; however, this was almost certainly unrelated to the MSC therapy. Conclusions: Using both high field MRI tracking and general surveillance in 227 patients, no neoplastic complications were detected at any stem cell re-implantation site. These findings are consistent with other reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs that were expanded in vitro for limited periods. PMID: 19951252 [PubMed - as supplied by publisher] |
| Clinical Applications of Mesenchymal Stem Cells in Laryngotracheal Reconstruction.
December 3, 2009 at 6:11 am
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| | Clinical Applications of Mesenchymal Stem Cells in Laryngotracheal Reconstruction. Curr Stem Cell Res Ther. 2009 Dec 2; Authors: Hanson S, Thibeault SL, Hematti P During the past several years, mesenchymal stem cells (MSCs) derived from adult tissue have rapidly moved from in vitro and animal studies into clinical trials as a therapeutic modality for a diverse group of clinical applications, including head and neck reconstruction. For many diseases, cell therapy could affect the underlying pathophysiologic processes through multiple pathways providing an advantage over current treatment modalities. There is an emerging body of evidence that MSCs have unique immunomodulatory properties in addition to the ability to differentiate into multiple tissue lineages which make them even more attractive for regenerative medicine. A variety of pre-clinical and clinical studies have shown that MSCs may have a useful role in tissue repair as well as engineering strategies in head and neck reconstructive surgery. Clinically, this has ranged from injection laryngoplasty to the implantation of a tracheal construct seeded with MSC-derived chondrocytes. Recent advances in stem cell immunobiology can offer insight to the multiple mechanisms through which MSCs could affect underlying pathophysiologic processes ranging from vocal fold scarring to composite tissue defects. Thorough evaluation of the current literature is necessary in understanding how MSCs could potentially revolutionize our approach to head and neck defects. The purpose of this review is to highlight the advances in MSC-based therapies in head and neck surgery, specifically laryngotracheal reconstruction. The clinical role of tissue-derived MSCs, though not well understood, holds promise for many therapeutic applications in regenerative medicine and reconstruction. PMID: 19951250 [PubMed - as supplied by publisher] | | | 
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