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| California Lawmakers to Weigh Stem Cell Agency Reform
February 17, 2010 at 4:48 PM
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| Just a few weeks after a key state panel recommended more accountability and transparency at the $3 billion California stem cell agency, a leading California lawmaker has proposed far-reaching changes in the five-year-old organization.
The measure – SB1064 by Sen. Elaine Alquist, D-San Jose – would require performance audits and thorough financial and leadership transition planning at CIRM. | | |
| Emerging gene and stem cell therapies for the treatment of erectile dysfunction.
February 17, 2010 at 8:43 AM
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| | Emerging gene and stem cell therapies for the treatment of erectile dysfunction. Nat Rev Urol. 2010 Feb 16; Authors: Harraz A, Shindel AW, Lue TF Erectile dysfunction is a prevalent condition that leads to significant morbidity and distress, not just for affected men but also for their partners. Very few currently available treatments ameliorate the underlying causes of the disorder and 'cure' the disease state. Much recent effort has been focused on the development of gene and cell-based approaches to rectify the molecular and tissue defects responsible for ED. Gene therapy has been investigated in animal models as a means to restore normal function to the penis; at this time, however, only one human trial has been published in the peer-reviewed literature. Recent gene therapy studies have focused on the modulation of enzymes associated with the NOS/cGMP pathway, and supplementation of trophic factors, peptides and potassium channels. Stem cell therapy has been a topic of interest in more recent years but there are currently very few published reports in animal models and none in human men. Although stem c! ell therapy offers the potential for restoration of functional tissues, legitimate concerns remain regarding the long-term fate of stem cells. The long-term safety of both gene and stem cell therapy must be thoroughly investigated before large-scale human studies can be considered. PMID: 20157303 [PubMed - as supplied by publisher] | | |
| Pluripotency maintenance mechanism of embryonic stem cells and reprogramming.
February 17, 2010 at 6:39 AM
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| | Pluripotency maintenance mechanism of embryonic stem cells and reprogramming. Int J Hematol. 2010 Feb 16; Authors: Masui S Embryonic stem (ES) cells are derived from blastocysts and are pluripotent. This pluripotency has attracted the interest of numerous researchers, both to expand our fundamental understanding of developmental biology and also because of potential applications in regenerative medicine. Systems biological studies have demonstrated that the pivotal transcription factors form a network. There they activate pluripotency-associated genes, including themselves, while repressing the developmentally regulated genes through co-occupation with various protein complexes. The chromatin structure characteristic of ES cells also contributes to the maintenance of the network. In this review, I focus on recent advances in our understanding of the transcriptional network that maintains pluripotency in mouse ES cells. PMID: 20157790 [PubMed - as supplied by publisher] | | |
| TAp63: The fountain of youth.
February 17, 2010 at 6:39 AM
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| | TAp63: The fountain of youth. Aging (Albany NY). 2009;1(10):866-9 Authors: Su X, Flores ER The mechanisms controlling organismal aging have yet to be clearly defined. In our recent paper [1], we revealed thatTAp63, the p53 family member, is a critical gene in preventing organismal aging by controlling the maintenance of dermal and epidermal precursor and stem cells critical for wound healing and hair growth. In the absence of TAp63, dermal stem cells (skin-derived precursors or SKPs) in young mice are hyperproliferative. As early as one month of age, SKPs and epidermal precursor cells exhibit signs of premature aging including a marked increase in senescence, DNA damage, and genomic instability resulting in an exhaustion of these cells and an overall acceleration in aging. Here, we discuss our findings and its relevance to longevity, regenerative medicine, and tumorigenesis. PMID: 20157559 [PubMed - in process] | | |
| A 3-dimensional extracellular matrix as a delivery system for the transplantation of glioma-targeting neural stem/progenitor cells.
February 17, 2010 at 6:39 AM
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| | A 3-dimensional extracellular matrix as a delivery system for the transplantation of glioma-targeting neural stem/progenitor cells. Neuro Oncol. 2010 Feb 14; Authors: Hansen K, Müller FJ, Messing M, Zeigler F, Loring JF, Lamszus K, Westphal M, Schmidt NO Neural stem/progenitor cells (NSPCs) display inherent pathotropic properties that can be exploited for targeted delivery of therapeutic genes to invasive malignancies in the central nervous system. Optimizing transplantation efficiency will be essential for developing relevant NSPC-based brain tumor therapies. To date, the real-world issue of handling and affixing NSPCs in the context of the neurosurgical resection cavity has not been addressed. Stem cell transplantation using biocompatible devices is a promising approach to counteract poor NSPC graft survival and integration in various types of neurological disorders. Here, we report the development of a 3-dimensional substrate that is based on extracellular matrix purified from tissue-engineered skin cultures (3DECM). 3DECM enables the expansion of embedded NSPCs in vitro while retaining their uncommitted differentiation status. When implanted in intracerebral glioma models, NSPCs were able to migrate out of the! 3DECM to targeted glioma growing in the contralateral hemisphere, and this was more efficient than the delivery of NSPC by intracerebral injection of cell suspensions. Direct application of a 3DECM implant into a tumor resection cavity led to a marked NSPC infiltration of recurrent glioma. The semisolid consistency of the 3DECM implants allowed simple handling during the surgical procedure of intracerebral and intracavitary application and ensured continuous contact with the surrounding brain parenchyma. Here, we demonstrate proof-of-concept of a matrix-supported transplantation of tumor-targeting NSPC. The semisolid 3DECM as a delivery system for NSPC has the potential to increase transplantation efficiency by reducing metabolic stress and providing mechanical support, especially when administered to the surgical resection cavity after brain tumor removal. PMID: 20156807 [PubMed - as supplied by publisher] | | |
| Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery.
February 17, 2010 at 6:39 AM
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| | Impacts of recent advances in cardiovascular regenerative medicine on clinical therapies and drug discovery. Pharmacol Ther. 2010 Feb 12; Authors: Murata M, Tohyama S, Fukuda K Although stem cell technology holds great promise for the treatment of degenerative diseases and the development of new drugs, progress has been hindered by immune and ethical problems in association with the use of embryonic stem cells (ESCs). The recent development of reprogramming of differentiated human somatic cells to pluripotent stem cells (iPSCs) should overcome these obstacles and facilitate clinical applications of stem cells. One of the advantages of reprogramming is that it allows the establishment of patient- and disease-specific in vitro models of human hereditary diseases for pathophysiologic and developmental studies. These in vitro models can be used for drug development and testing, moving us a step closer to personalized therapies. This review outlines the current status of pluripotent stem cells and focuses on the potential applications of stem-cell derived cardiomyocytes for clinical therapies, as well as for drug development and testing. PMID: 20156482 [PubMed - as supplied by publisher] | | |
| Recents Patents for Isolating, Delivering and Tracking Adult Stem Cells in Regenerative Medicine.
February 17, 2010 at 6:39 AM
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| | Recents Patents for Isolating, Delivering and Tracking Adult Stem Cells in Regenerative Medicine. Recent Pat Drug Deliv Formul. 2010 Feb 16; Authors: Fierabracci A The field of regenerative medicine offers nowadays the potential to significantly impact a wide spectrum of healthcare issues, from insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering biomaterials, biological factors, regeneration competent cells are used in the process of creating functional tissue. Regarding the type of stem or progenitor cells which represents the best candidate for therapy, embryonic stem cells have been considered the master cells capable of differentiating into every type of cells either in vitro or in vivo, in spite of serious ethical concerns. Nevertheless experimental evidence suggests that adult stem cells and even terminally differentiated somatic cells under appropriate microenvironmental treatments can be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. One of the main goals is to exploit novel technologies aiming to isol! ate, expand and enrich sources of regeneration competent cells, expecially adult somatic stem cells. Researchers are also trying to develop innovative strategies for effectively delivering regenerative cell populations and to implement 'tracking' tools to verify their engraftment and destiny in vivo. Here we review recent patents on the field issued over the past five years. PMID: 20156176 [PubMed - as supplied by publisher] | | |
| Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering.
February 17, 2010 at 6:39 AM
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| | Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering. Tissue Eng Part A. 2010 Feb 16; Authors: Nakayama KH, Batchelder CA, Lee CC, Tarantal A The goal of this study was the production of a decellularized kidney scaffold with structural, mechanical, and physiological properties necessary for engineering basic renal structures <i>in vitro</i>. Fetal, infant, juvenile, and adult rhesus monkey kidney sections were treated with either 1% (v/v) sodium dodecyl sulfate (SDS) or Triton X-100 followed by quantitative and qualitative analysis. Comparison of decellularization agents and incubation temperatures demonstrated SDS at 4 degrees C to be most effective in preserving the native architecture. Hematoxylin and eosin staining confirmed the removal of cellular material and immunohistochemistry demonstrated preservation of native expression patterns of extracellular matrix (ECM) proteins including heparan sulfate proteoglycan, fibronectin, collagen types I and IV, and laminin. Biomechanical testing revealed a decrease in the compressive modulus of decellularized compared to fresh kidneys. Layering of! fetal kidney explants on age-matched decellularized kidney scaffolds demonstrated the capacity of the scaffold to support Pax2+/vimentin+ cell attachment and migration to recellularize the scaffold. These findings demonstrate that decellularized kidney sections retains critical structural and functional properties necessary for use as a three-dimensional scaffold and promotes cellular repopulation. Furthermore, this study provides the initial steps in developing new regenerative medicine strategies for renal tissue engineering and repair. PMID: 20156112 [PubMed - as supplied by publisher] | | |
| Bio-interfaces-Interaction of PLL/HA Thick Films with Nanoparticles and Microcapsules.
February 17, 2010 at 6:21 AM
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| | Bio-interfaces-Interaction of PLL/HA Thick Films with Nanoparticles and Microcapsules. Chemphyschem. 2010 Feb 15; Authors: Skirtach AG, Volodkin DV, Möhwald H The interaction of biocompatible, exponentially grown films composed of poly-L-lysine (PLL) and hyaluronic acid (HA) polymers with gold nanoparticles and microcapsules is studied. Both aggregated and non-aggregated nanoparticle states are achieved; desorption of PLL accounts for aggregation of nanoparticles. The presence of aggregates of gold nanoparticles on films enables remote activation by near-infrared irradiation due to local, nanometer confined heating. Thermally shrunk microcapsules, which are remarkably monodisperse upon preparation but gain polydispersity after months of storage, are also adsorbed onto films. PLL polymers desorbed from films interact with microcapsules introducing a charge imbalance which leads to an increase of the microcapsule size, thus films amplify this effect. Multifunctional, biocompatible, thick gel films with remote activation and release capabilities are targeted for cell cultures in biology and tissue engineering in medicine. PMID: 20157913 [PubMed - as supplied by publisher] | | |
| Nanomaterials for in situ cell delivery and tissue regeneration.
February 17, 2010 at 6:21 AM
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| | Nanomaterials for in situ cell delivery and tissue regeneration. Adv Drug Deliv Rev. 2010 Feb 12; Authors: Wan AC, Ying JY Nanomaterials can be defined as materials that possess clearly defined features of less than 100 nm, and whose nanostructured features confer characteristics crucial to the material's bulk property. The nanostructured features can be an intermediate or final state of the material in its synthesis process. The field of nanomaterials as applied to in situ cell delivery and tissue engineering is rapidly expanding. Nanomaterials that include peptide amphiphiles, self-assembling peptides, electrospun scaffolds, layer-by-layer complexes, nanotubes and nanocomposites have been applied to cell culture, encapsulation and delivery with promising results. As compared to scaffold-free cell delivery, nanomaterials are advantageous in terms of providing a means to control the biochemical and mechanical microenvironment of the cells. Nanomaterials are amenable to a bottom-up approach in functionalization and mechanical tuning, as illustrated in the examples presented this review! . Furthermore, nanomaterials such as DNA polyplexes and carbon nanotubes can also be incorporated into the cell delivery vehicle to improve the regenerative outcome. Lastly, while nanomaterials harbor much potential for cell delivery and tissue regeneration, further characterization is required in terms of clinical safety before these materials can be employed towards therapeutic applications. PMID: 20156499 [PubMed - as supplied by publisher] | | |
| Induction of tumoricidal activity in mouse peritoneal macrophages by ginseng polysaccharide.
February 17, 2010 at 6:21 AM
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| | Induction of tumoricidal activity in mouse peritoneal macrophages by ginseng polysaccharide. Int J Biol Macromol. 2010 Feb 12; Authors: Wang J, Zuo G, Li J, Guan T, Li C, Jiang R, Xie B, Lin X, Li F, Wang Y, Chen D This study examined the effects of ginseng polysaccharide (GPS) on mouse peritoneal macrophage(PM)-mediated cytotoxicity towards K562, HL-60, or KG1alpha cells. GPS had no direct effect on killing of tumor cells. However, when mouse PMs were treated with GPS, cytotoxic activity against K562, HL-60, or KG1alpha cells was significantly induced. In addition, phagocytic activity was enhanced in GPS-treated mouse PMs compared to the control. The expressions of CD(68), ACP and alpha-ANE in mouse PMs were increased by the treatment with GPS. Moreover, the levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), IL-6 were increased and the production of nitric oxide (NO) was enhanced. Taken together, these results suggest that GPS possess a potent anti-tumor activity by stimulating macrophage and a potentiality as an immunomodulator against diseases such as cancer. PMID: 20156477 [PubMed - as supplied by publisher] | | |
| Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity.
February 17, 2010 at 6:21 AM
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| | Mechanosensitivity of dental pulp stem cells is related to their osteogenic maturity. Eur J Oral Sci. 2010 Feb;118(1):29-38 Authors: Kraft DC, Bindslev DA, Melsen B, Abdallah BM, Kassem M, Klein-Nulend J For engineering bone tissue, mechanosensitive cells are needed for bone (re)modelling. Local bone mass and architecture are affected by mechanical loading, which provokes a cellular response via loading-induced interstitial fluid flow. We studied whether human dental pulp-derived mesenchymal stem cells (PDSCs) portraying mature (PDSC-mature) or immature (PDSC-immature) bone cell characteristics are responsive to pulsating fluid flow (PFF) in vitro. We also assessed bone formation by PDSCs on hydroxyapatite-tricalcium phosphate granules after subcutaneous implantation in mice. Cultured PDSC-mature exhibited higher osteocalcin and alkaline phosphatase gene expression and activity than PDSC-immature. Pulsating fluid flow (PFF) stimulated nitric oxide production within 5 min by PDSC-mature but not by PDSC-immature. In PDSC-mature, PFF induced prostaglandin E(2) production, and cyclooxygenase 2 gene expression was higher than in PDSC-immature. Implantation of PDSC-matu! re resulted in more osteoid deposition and lamellar bone formation than PDSC-immature. We conclude that PDSCs with a mature osteogenic phenotype are more responsive to pulsating fluid shear stress than osteogenically immature PDSCs and produce more bone in vivo. These data suggest that PDSCs with a mature osteogenic phenotype might be preferable for bone tissue engineering to restore, for example, maxillofacial defects, because they might be able to perform mature bone cell-specific functions during bone adaptation to mechanical loading in vivo. PMID: 20156262 [PubMed - in process] | | |
| Recents Patents for Isolating, Delivering and Tracking Adult Stem Cells in Regenerative Medicine.
February 17, 2010 at 6:21 AM
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| | Recents Patents for Isolating, Delivering and Tracking Adult Stem Cells in Regenerative Medicine. Recent Pat Drug Deliv Formul. 2010 Feb 16; Authors: Fierabracci A The field of regenerative medicine offers nowadays the potential to significantly impact a wide spectrum of healthcare issues, from insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) to cardiovascular disease. In tissue engineering biomaterials, biological factors, regeneration competent cells are used in the process of creating functional tissue. Regarding the type of stem or progenitor cells which represents the best candidate for therapy, embryonic stem cells have been considered the master cells capable of differentiating into every type of cells either in vitro or in vivo, in spite of serious ethical concerns. Nevertheless experimental evidence suggests that adult stem cells and even terminally differentiated somatic cells under appropriate microenvironmental treatments can be reprogrammed and contribute to a much wider spectrum of differentiated progeny than previously anticipated. One of the main goals is to exploit novel technologies aiming to isol! ate, expand and enrich sources of regeneration competent cells, expecially adult somatic stem cells. Researchers are also trying to develop innovative strategies for effectively delivering regenerative cell populations and to implement 'tracking' tools to verify their engraftment and destiny in vivo. Here we review recent patents on the field issued over the past five years. PMID: 20156176 [PubMed - as supplied by publisher] | | |
| Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering.
February 17, 2010 at 6:21 AM
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| | Decellularized Rhesus Monkey Kidney as a Three-Dimensional Scaffold for Renal Tissue Engineering. Tissue Eng Part A. 2010 Feb 16; Authors: Nakayama KH, Batchelder CA, Lee CC, Tarantal A The goal of this study was the production of a decellularized kidney scaffold with structural, mechanical, and physiological properties necessary for engineering basic renal structures <i>in vitro</i>. Fetal, infant, juvenile, and adult rhesus monkey kidney sections were treated with either 1% (v/v) sodium dodecyl sulfate (SDS) or Triton X-100 followed by quantitative and qualitative analysis. Comparison of decellularization agents and incubation temperatures demonstrated SDS at 4 degrees C to be most effective in preserving the native architecture. Hematoxylin and eosin staining confirmed the removal of cellular material and immunohistochemistry demonstrated preservation of native expression patterns of extracellular matrix (ECM) proteins including heparan sulfate proteoglycan, fibronectin, collagen types I and IV, and laminin. Biomechanical testing revealed a decrease in the compressive modulus of decellularized compared to fresh kidneys. Layering of! fetal kidney explants on age-matched decellularized kidney scaffolds demonstrated the capacity of the scaffold to support Pax2+/vimentin+ cell attachment and migration to recellularize the scaffold. These findings demonstrate that decellularized kidney sections retains critical structural and functional properties necessary for use as a three-dimensional scaffold and promotes cellular repopulation. Furthermore, this study provides the initial steps in developing new regenerative medicine strategies for renal tissue engineering and repair. PMID: 20156112 [PubMed - as supplied by publisher] | | |
| [Repair alveolar cleft bone defects with bone marrow stromal cells]
February 17, 2010 at 6:21 AM
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| | [Repair alveolar cleft bone defects with bone marrow stromal cells] Zhonghua Zheng Xing Wai Ke Za Zhi. 2006 Nov;22(6):409-11 Authors: Chai G, Zhang Y, Hu XJ, Wang M, Liu W, Cui L, Cao YL OBJECTIVE: To explore the feasibility of repairing alveolar cleft bone defects with bone marrow stromal cells. METHODS: Total 7 patients of alveolar cleft were included in this study. The hBMSCs were isolated by percoll gradient centrifugation from patient's bone marrow aspirated from iliac crest. The hBMSCs were cultured in vitro and induced to become osteogenic cells in the DMEM medium containing 10% self-serum, beta-glycerophosphate (10 nmol/L) dexamethasone (10(-8) mol/L) , L-2-ascorbic acid(50 micromol/L), and 1, 25 (OH)2 VD3 (10 nmol/L). Induced hBMSCs of passage 3 were harvested and seeded onto partly demineralized allogenic bone matrix (pDBM) to form a cell-scaffold construct and in vitro co-culture for 1 week. The defects were repaired with the cell-scaffold construct. All cases were followed up for 3, 6 months post-operation as short-term evaluation and 1 to 3 years post-operation as long-term evaluation by three-dimensional computerized tomography (3D-C! T) and clinical examination. RESULTS: 3D-CT demonstrated that engineered bone was formed in 3 months post-operation. Additionally, formed bone maintained stable up to 1 - 3 years without absorption. CONCLUSIONS: Engineered bone can be used to repair clinical alveolar cleft bone defects. PMID: 17285993 [PubMed - indexed for MEDLINE] | | |
| [Effects of BMP-2 gene therapy on vascularization in repairing bone defects]
February 17, 2010 at 6:21 AM
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| | [Effects of BMP-2 gene therapy on vascularization in repairing bone defects] Zhonghua Zheng Xing Wai Ke Za Zhi. 2006 Jul;22(4):303-5 Authors: Li JJ, Zhao Q, Sun HB, Han D, Han D, Xu XX OBJECTIVE: To study the effects of BMP-2 gene therapy on vascularization in repairing bone defects. METHODS: The isolated rabbit mesenchymal stem cells (rBMSC), after being transfected by adenovirus carrying BMP-2 gene (Ad-BMP-2) and seeded on xenogeneic bone scaffolds, were used to repair 1.5 cm-long radius bone defects. Five methods were in use in the experiments: Ad-BMP-2 infected rBMSC plus antigen-free bovine cancellous bone (BCB, Group A), rBMSC-BCB plus reconstructed hBMP-2 (Group B1), Ad-LacZ infected rBMSC-BCB (Group C), rBMSC-BCB (Group D) and only BCB scaffolds (Group E). After 4, 8, and 12 weeks of the operations, capillary vessel ink infusion, vascular endothelial growth factor ( VEGF) immunohistochemical staining and histological examination were conducted. RESULTS: After 4 weeks of the operations, usually in Group A one newly formed artery was found in every pore between the trabeculae of the BCB. The density of these intraosseous vessels was high i! n the periphery and decreasing towards the center of the grafts; by transmission electron microscopy, osteoblasts were always next to vascular endothelial cells and gradually developed into osteocytes with the increase of capillary vessel; VEGF expression were apparently enhanced in mesenchymocytes. CONCLUSIONS: BMP-2 gene therapy, by up-regulating VEGF expression, indirectly induces vascularization of grafts and is of great value to the treatment of bone in union and bone defects. PMID: 17017149 [PubMed - indexed for MEDLINE] | | |
| [Implantation of neonatal cardiomyocytes plus artificial matrix improve heart function in a rat infarct model]
February 17, 2010 at 6:21 AM
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| | [Implantation of neonatal cardiomyocytes plus artificial matrix improve heart function in a rat infarct model] Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Oct;33(10):922-6 Authors: Zhang PC, Zhang H, Hu SS, Wang H, Wei YJ OBJECTIVE: To investigate whether injectable engineering heart tissue (EHT) can survive and improve heart function after transplantation into infarct area. METHODS: Ventricular cardiomyocytes from 1-3 day-old Sprague-Dawley (SD) rats were isolated by using trypsin method, and then labeled and cultured. The left coronary of female SD rats was ligated to create a myocardial infarct model. Three weeks later, the qualified animals were randomized into four groups: EHT group (n = 12), which were transplanted with both cardiomyocytes and matrix; cell transplantation group (n = 12); matrix group (n = 12), control (n = 11). Four weeks after implantation, echocardiography and Langendorff model were used to assess heart function, and then the hearts were harvested for pathological examination. Meanwhile polymerase chain reaction (PCR) was performed to detect SRY gene on Y chromosome. RESULTS: The grafted cells were identified in both EHT and cell transplantation group by ei! ther pathology or PCR. But in EHT group, transplanted cells formed more condensed tissue, and produced definite connected protein. Data of fraction shortness from echocardiography are showed as follows: EHT group, (22.82 +/- 3.44)%; cell transplantation group, (20.55 +/- 4.11)%, matrix group, (17.05 +/- 4.57)%; control, (19.80 +/- 3.98)% (P = 0.012). Langendorff examination revealed significant differences among four groups when left ventricular balloon volume was at the level of 0.06 ml, 0.08 ml and 0.10 ml, in which EHT group had the highest developed pressure and dp/dt. CONCLUSION: It is feasible to fabricate injectable EHT in vitro. The fabricated EHT could survive in the myocardial infarct area after transplantation in a rat model and improve heart function due to better histological configuration. PMID: 16266483 [PubMed - indexed for MEDLINE] | | | | 
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