Friday, October 16, 2009

10/17 TE-RegenMed-StemCell feed

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Square 1 Wins CIRM Biotech Loan Pilot Project
October 16, 2009 at 5:11 pm

The California stem cell agency has signed a $250,000 contract with Square 1 bank to perform a financial review of the firms seeking the first-ever CIRM loans in a program that could reach $500 million or so.In response to a query, Don Gibbons, chief communications officer for CIRM, said today that the fee-for-service arrangement covered only this year's $210 million disease team round, which is

New findings on the formation of body pigment
October 16, 2009 at 12:54 pm


Scientists demonstrate link between genetic defect and brain changes in schizophrenia
October 16, 2009 at 11:54 am


Internationally highly visible
October 16, 2009 at 9:49 am


Papers from the Second International Conference on the Mechanics of Biomaterials and Tissues, 2007.
October 16, 2009 at 6:53 am

Papers from the Second International Conference on the Mechanics of Biomaterials and Tissues, 2007.

J Mech Behav Biomed Mater. 2009 Apr;2(2):129-216

Authors:

PMID: 19830905 [PubMed - indexed for MEDLINE]


Conductive Core-Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering.
October 16, 2009 at 6:53 am

Conductive Core-Sheath Nanofibers and Their Potential Application in Neural Tissue Engineering.

Adv Funct Mater. 2009 Jul 24;19(14):2312-2318

Authors: Xie J, Macewan MR, Willerth SM, Li X, Moran DW, Sakiyama-Elbert SE, Xia Y

We have prepared conductive core-sheath nanofibers via a combination of electrospinning and aqueous polymerization. Specifically, nanofibers electrospun from poly(epsilon-caprolactone) (PCL) and poly((L)-lactide) (PLA) were employed as templates to generate uniform sheaths of polypyrrole (PPy) via in situ polymerization. These conductive core-sheath nanofibers offer a unique system for studying the synergistic effect of different cues on neurite outgrowth in vitro. We found that explanted dorsal root ganglia (DRG) adhered well to the conductive core-sheath nanofibers and generated neurites across the surface when there was a nerve growth factor in the medium. Furthermore, the neurites could be oriented along one direction and enhanced by 82% in terms of maximum length when uniaxially aligned conductive core-sheath nanofibers are compared with their random counterparts. Electrical stimulation, when applied through the mats of conductive core-sheath nanofibers, was found to further increase the maximum length of neurite for random and aligned samples by 83% and 47%, respectively, relative to the controls without electrical stimulation. Combined together, these results suggest the potential use of the conductive core-sheath nanofibers as scaffolds in applications such as neural tissue engineering.

PMID: 19830261 [PubMed - as supplied by publisher]


Tissue engineering in urology.
October 16, 2009 at 6:53 am

Tissue engineering in urology.

Can Urol Assoc J. 2009 Oct;3(5):403-408

Authors: Matoka DJ, Cheng EY

Tissue engineering encompasses a multidisciplinary approach geared toward the development of biological substitutes designed to restore and maintain normal function in diseased or injured tissues. This article reviews the basic technology that is used to generate implantable tissue-engineered grafts in vitro that will exhibit characteristics in vivo consistent with the physiology and function of the equivalent healthy tissue. We also examine the current trends in tissue engineering designed to tailor scaffold construction, promote angiogenesis and identify an optimal seeded cell source. Finally, we describe several currently applied therapeutic modalities that use a tissue-engineered construct. While notable progress has clearly been demonstrated in this emerging field, these efforts have not yet translated into widespread clinical applicability. With continued development and innovation, there is optimism that the tremendous potential of this field will be realized.

PMID: 19829737 [PubMed - as supplied by publisher]


Nanostructure-Biomolecule Interactions: Implications for Tissue Regeneration and Nanomedicine.
October 16, 2009 at 6:53 am

Nanostructure-Biomolecule Interactions: Implications for Tissue Regeneration and Nanomedicine.

Tissue Eng Part A. 2009 Oct 14;

Authors: Nuffer J, Siegel R

Great strides are being made worldwide in our ability to synthesize and assemble nanoscale building blocks to create advanced materials with novel properties and functionalities. The novel properties of nanostructures are derived from their confined sizes and their very large surface-to-volume ratios. Nanostructured surfaces have also been shown to elicit more favorable and selective biomolecule and cellular responses than surfaces at coarser length scales. In the case of nanoscale ceramics and osteoblasts, for example, the benefit results from protein (vitronectin) unfolding at the nanostructured surface. These nanoscale attributes are enabling a variety of nanostructures to form the bases for a new field - nanomedicine. A fundamental issue in much of nanomedicine, and especially tissue regeneration, is to understand and to eventually control nanostructure-biomolecule interactions. In order to elucidate the fundamental bases for changes of protein conformation and function on nanostructured surfaces, and hence select responses including those of stem cells, a number of model experiments have been carried out. The results of these studies are presented and discussed in the context of the fundamental driving forces for protein conformation changes associated with nanostructures, their relationship to modified cell responses and tissue engineering, and our present knowledge regarding nanostructure properties.

PMID: 19827941 [PubMed - as supplied by publisher]


Isolating Osteogenic Progenitor Cells From Trabecular Bone For Bone Tissue Engineering.
October 16, 2009 at 6:53 am

Isolating Osteogenic Progenitor Cells From Trabecular Bone For Bone Tissue Engineering.

Tissue Eng Part A. 2009 Oct 14;

Authors: Yoshii T, Sotome S, Torigoe I, Maehara H, Sugata Y, Yamada T, Shinomiya K, Okawa A

Trabecular bone fragments can be percutaneously harvested from the ilium using methods that are similar in invasiveness to aspiration of bone marrow. In this study, we investigated the use of the trabecular bone as a cell source for bone tissue engineering. Trabecular bone derived progenitor cells (TB cells) were isolated with a simple method in which trabecular fragments were first cultured as explants, and then the cells were released by trypsin digestion and advanced to a monolayer culture. The properties of TB cells prepared in this procedure were compared with bone marrow derived progenitor cells (BM cells). A large number of TB cells could be obtained with less variation among donors, compared to BM cells. In multiple harvests of donor tissue through the same aspiration hole at the cortex, TB cells could be more consistently obtained in primary culture. The proliferative potential of BM and TB cells was similar in serial subculture. TB cells showed a higher ALP expression in the surface marker analysis and greater in vitro osteogenic abilities than BM cells after the initial 14 days of culture. In in vivo bone formation studies, TB cells also showed a higher osteogenic potential than BM cells. The results of this study suggest that TB cells can be considered an attractive source for clinical bone regeneration.

PMID: 19827915 [PubMed - as supplied by publisher]


On the road to iPS cell cardiovascular applications.
October 16, 2009 at 6:53 am

Related Articles

On the road to iPS cell cardiovascular applications.

Circ Res. 2009 Sep 25;105(7):617-9

Authors: Kamp TJ, Lyons GE

PMID: 19797193 [PubMed - indexed for MEDLINE]


iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism.
October 16, 2009 at 6:53 am

iPS programmed without c-MYC yield proficient cardiogenesis for functional heart chimerism.

Circ Res. 2009 Sep 25;105(7):648-56

Authors: Martinez-Fernandez A, Nelson TJ, Yamada S, Reyes S, Alekseev AE, Perez-Terzic C, Ikeda Y, Terzic A

RATIONALE: Induced pluripotent stem cells (iPS) allow derivation of pluripotent progenitors from somatic sources. Originally, iPS were induced by a stemness-related gene set that included the c-MYC oncogene. OBJECTIVE: Here, we determined from embryo to adult the cardiogenic proficiency of iPS programmed without c-MYC, a cardiogenicity-associated transcription factor. METHODS AND RESULTS: Transgenic expression of 3 human stemness factors SOX2, OCT4, and KLF4 here reset murine fibroblasts to the pluripotent ground state. Transduction without c-MYC reversed cellular ultrastructure into a primitive archetype and induced stem cell markers generating 3-germ layers, all qualifiers of acquired pluripotency. Three-factor induced iPS (3F-iPS) clones reproducibly demonstrated cardiac differentiation properties characterized by vigorous beating activity of embryoid bodies and robust expression of cardiac Mef2c, alpha-actinin, connexin43, MLC2a, and troponin I. In vitro isolated iPS-derived cardiomyocytes demonstrated functional excitation-contraction coupling. Chimerism with 3F-iPS derived by morula-stage diploid aggregation was sustained during prenatal heart organogenesis and contributed in vivo to normal cardiac structure and overall performance in adult tumor-free offspring. CONCLUSIONS: Thus, 3F-iPS bioengineered without c-MYC achieve highest stringency criteria for bona fide cardiogenesis enabling reprogrammed fibroblasts to yield de novo heart tissue compatible with native counterpart throughout embryological development and into adulthood.

PMID: 19696409 [PubMed - indexed for MEDLINE]


Encapsulation of living cells in small ( approximately 100 microm) alginate microcapsules by electrostatic spraying: a parametric study.
October 16, 2009 at 6:53 am

Related Articles

Encapsulation of living cells in small ( approximately 100 microm) alginate microcapsules by electrostatic spraying: a parametric study.

J Biomech Eng. 2009 Jul;131(7):074515

Authors: Zhang W, He X

A parametric study was performed to understand the effect of preparation parameters on size, morphology, and encapsulation efficiency (i.e., cells/microcapsule) of alginate microcapsules prepared using the electrostatic spray method. The preparation parameters studied include sodium alginate concentration, spray voltage, flow rate, and cell density. It was found that both the flow rate and spray voltage have a significant impact on microcapsule size while the microcapsule morphology is greatly influenced by both the sodium alginate concentration and spray voltage. To obtain small ( approximately 100 mum) cell-loaded microcapsules with good morphology (i.e., round in shape and uniform in size) and high encapsulation efficiency (>5 cells/microcapsule), the optimal ranges of spray voltage, flow rate, alginate concentration, and cell density are from 1.6-1.8 kV, 1.5-3 ml/h, >1.5% (w/v), and (3-5)x10(6) cells/ml, respectively. Under optimal preparation conditions, cells were found to survive the microencapsulation process well.

PMID: 19640151 [PubMed - indexed for MEDLINE]


Clinical Center of Serbia, Institute for Cardiovascular Diseases Treats First Patient in Trial of Pioneering Stem Cell-Derived Therapy for Heart Failure
October 16, 2009 at 6:48 am


Stem Cells with Neural Crest Characteristics Derived from the Bulge Region of Cultured Human Hair Follicles.
October 16, 2009 at 6:45 am

Stem Cells with Neural Crest Characteristics Derived from the Bulge Region of Cultured Human Hair Follicles.

J Invest Dermatol. 2009 Oct 15;

Authors: Yu H, Kumar SM, Kossenkov AV, Showe L, Xu X

In this study, we demonstrate that we can isolate stem cells (SCs) with neural crest characteristics from the bulge area of cultured human hair follicles (HFs). These SCs can proliferate in situ and form spheroid structures attached to the bulge area of HFs, and they express immature neural crest cell markers but not differentiation markers. An expression profiling study showed that they share a similar gene expression pattern with murine skin immature neural crest cells. These human SCs are label-retaining cells and are capable of self-renewal through asymmetric cell division in vitro. They exhibit clonal multipotency that can give rise to myogenic, melanocytic, and neuronal cell lineages after in vitro clonal single cell culture. In addition, these SCs show differentiation potential toward mesenchymal lineages, and they can be differentiated into adipocyte, chondrocyte, and osteocyte lineages. Neuronal differentiation of these cells induces global gene expression changes with a significantly increased expression of neuron-associated genes. Differentiated neuronal cells can persist in mouse brain and retain neuronal differentiation markers. The presence of SCs with neural crest characteristics in HFs may offer new opportunities for the use of these cells in regenerative medicine.Journal of Investigative Dermatology advance online publication, 15 October 2009; doi:10.1038/jid.2009.322.

PMID: 19829300 [PubMed - as supplied by publisher]


Fetal-maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease.
October 16, 2009 at 6:45 am

Fetal-maternal exchange of multipotent stem/progenitor cells: microchimerism in diagnosis and disease.

Trends Mol Med. 2009 Oct 12;

Authors: Klonisch T, Drouin R

The biological concept of microchimerism, the bidirectional trafficking and stable long-term persistence of small numbers of allogeneic (fetal and maternal) cells in a genetically different organ, has gained considerable attention. Microchimerism is a common phenomenon in many species, including humans, and microchimeric cells can modify immunological recognition or tolerance, affect the course and outcome of various diseases and demonstrate stem cell-like or regenerative potential. Here, we review current knowledge of the biology of microchimerism and show how long-term allogeneic co-existence within an organism can impact on existing paradigms in chronic disease, cancer biology, regenerative medicine and fetal-maternal immunology. We discuss diagnostic challenges, clinical applications and future research directions in this exciting and rapidly emerging field of allogeneic fetal-maternal cell exchange.

PMID: 19828378 [PubMed - as supplied by publisher]


How does inflammation cause Barrett's metaplasia?
October 16, 2009 at 6:45 am

How does inflammation cause Barrett's metaplasia?

Curr Opin Pharmacol. 2009 Oct 12;

Authors: Colleypriest BJ, Ward SG, Tosh D

Oesophageal adenocarcinoma conveys a poor prognosis and has a rapidly increasing incidence. Similarly, Barrett's metaplasia (a precursor lesion for oesophageal adenocarcinoma) has an increasing incidence. Both oesophageal adenocarcinoma and Barrett's metaplasia are more common in the context of inflammation as a result of acid and bile reflux. The cytokine profile of Barrett's metaplasia is predominantly a T-helper 2 response that contrasts with the T-helper 1 response in normal and inflamed oesophagus and normal intestine. A key transcription factor in the development of Barrett's metaplasia, CDX2, has recently been shown to be induced in response to inflammatory mediators. The mechanism for induction of CDX2 is dependent on nuclear factor kappa B, a crucial transcription factor in the inflammatory response. Understanding the role of oesophageal inflammation will provide important insight into the development of Barrett's metaplasia and oesophageal cancer.

PMID: 19828375 [PubMed - as supplied by publisher]


Surface characterization of extracellular matrix scaffolds.
October 16, 2009 at 6:45 am

Surface characterization of extracellular matrix scaffolds.

Biomaterials. 2009 Oct 12;

Authors: Brown BN, Barnes CA, Kasick RT, Michel R, Gilbert TW, Beer-Stolz D, Castner DG, Ratner BD, Badylak SF

Extracellular matrix (ECM) scaffolds prepared from different tissue sources or using different methods have been demonstrated to have distinctive effects upon cell adhesion patterns and the ability to support and maintain differentiated phenotypes. It is unknown whether the molecular composition or the ultrastructure of the ECM plays a greater role in determining the phenotype of the cells with which it comes into contact. However, when implanted, the topology and ligand landscape of the material will determine the host molecules that bind and the type and behavior of cells that mediate the host response. Therefore, a comprehensive understanding of surface characteristics is essential in the design of scaffolds for specific clinical applications. The surface characteristics of ECM scaffolds derived from porcine urinary bladder, small intestine, and liver as well as the effects of two commonly used methods of chemical cross-linking upon UBM were investigated. Electron microscopy and time of flight secondary ion mass spectroscopy were used to examine the surface characteristics of the scaffolds. The results show that ECM scaffolds have unique morphologic and structural properties which are dependant on the organ or tissue from which the scaffold is harvested. Furthermore, the results show that the surface characteristics of an ECM scaffold are changed through chemical cross-linking.

PMID: 19828192 [PubMed - as supplied by publisher]


Innate immunity of the ocular surface.
October 16, 2009 at 6:45 am

Innate immunity of the ocular surface.

Brain Res Bull. 2009 Oct 11;

Authors: Ueta M, Kinoshita S

The ocular surface epithelium serves a critical function as the defensive front line of the innate immune system. While the detection of microbes is arguably its most important task, an exaggerated host defense reaction to endogenous bacterial flora may initiate and perpetuate inflammatory mucosal responses. The ability of cells to recognize pathogen-associated molecular patterns (PAMPs) mainly depends on the expression of a family of Toll-like receptors (TLRs). A healthy ocular surface is not inflammatory, even though ocular surface epithelium is in constant contact with bacteria and bacterial products. In this study, we show that human ocular surface epithelial cells, both corneal and conjuctival epithelial cells, respond to viral double-stranded RNA mimic polyI:C to produce pro-inflammatory cytokines through TLR3, while they fail to respond functionally to lipopolysaccharide, a TLR4 ligand. Moreover, human ocular surface epithelium responds to flagellins from ocular pathogenic, but not ocular non-pathogenic bacteria, to produce pro-inflammatory cytokines through TLR5. Thus, ocular surface epithelial cells selectively respond to microbial components and induce limited inflammation; immune-competent cells can recognize microbial components through TLRs and induce the inflammation. The unique innate immune response of the ocular surface epithelium may contribute to its coexistence with commensal bacteria.Inflammatory bowel disease is thought to result from an abnormal response to the gut microbiota. Thus, we also considered the possibility of an association between ocular surface inflammation and a disordered innate immune response. IkappaBzeta is important for TLR signaling, In mice, its knock-out produced severe, spontaneous ocular surface inflammation, the eventual loss of goblet cells, and spontaneous perioral inflammation, suggesting that dysfunction/abnormality of innate immunity can lead to ocular surface inflammation.

PMID: 19828129 [PubMed - as supplied by publisher]


Role of hypoxia in stem cell development and functioning.
October 16, 2009 at 6:45 am

Role of hypoxia in stem cell development and functioning.

Fiziol Zh. 2009;55(4):116-30

Authors: Nikolsky I, Serebrovska TV

The response of stem cells (SC) to hypoxia is one of the main mechanisms of an organism's adaptation to changing terms of external and internal environment. This review describes the role of hypoxia in functioning of various stem cell, types--embryonic, hematopoietic, nmesenchvmal and neural, paying special attention to the very limited data concerning intermittent hypoxia (IH) effects. All stem cells and their precursors exist in microenvironment named stem cell niches. The most crucial factor for their normal functioning is hypoxia. which contributes to maintaining the SC in quiescent state with necessary rate of self-renewal. The key element qf these mechanisms is a complex of hypoxia-inducible transcription factors. An additional exogenous hypoxic impact leads to activation of SC system. Very scant information on IH effects on SC that was obtained generally in cell culture models, reveals that intermittent hypoxia at certain duration and intensity is a more potent trigger of transcription activation than constant hypoxia. In the future a method of IH training/treatment could be effectively used for correction of physiological changes and pathological disorders in art organism.

PMID: 19827638 [PubMed - in process]


[Cord blood banking]
October 16, 2009 at 6:45 am

[Cord blood banking]

Acta Med Croatica. 2009 Jun;63(3):245-50

Authors: Cepulić BG, Bojanić I, Mazić S

Transplantation of cord blood stem cells is a new and rapidly developing area. It has been used as a treatment for many diseases such as hematologic malignancies, primary immune deficiencies and metabolic diseases. Recently, stem cells have been used in regenerative medicine, particularly in neurodegenerative and cardiovascular diseases. For these reasons interest has been growing in banking cord blood. To be able to find an acceptable donor for any recipient in need, it is necessary to have on stock a great diversity of cells with different genetic types from different populations. Networks of banks and registries have been created around the world in order to share and exchange transplants. Public banks organize collection for altruistic donor of cord blood for unrelated hematopoietic stem cell transplantation and for directed donation in families at risk. But there are increasing numbers of families that are requesting storage of cord blood for possible future therapeutic use in the family. Establishment of cord blood banks has raised a number of important scientific, legal, ethical and political issues, which are discussed in this paper.

PMID: 19827353 [PubMed - in process]


[Trends in stem cell manipulation ex vivo]
October 16, 2009 at 6:45 am

[Trends in stem cell manipulation ex vivo]

Acta Med Croatica. 2009 Jun;63(3):231-6

Authors: Batinić D

Hematopoietic stem cell transplantation (HSCT) is nowadays a standard procedure for the treatment of malignant and non-malignant diseases of bone marrow and immune system as well as of malignant solid tumors. However, HSCT is often complicated by serious and often fatal conditions, which initiated development of a number of techniques of cell manipulation ex vivo in the last two decades, with the aim of improving the graft quality and thus the outcome of transplantation. The subject of this brief review is graft manipulation in autologous and allogeneic HSCT, with emphasis on the future directions in cell therapy and regenerative medicine.

PMID: 19827351 [PubMed - in process]


Strategies for future histocompatible stem cell therapy.
October 16, 2009 at 6:45 am

Related Articles

Strategies for future histocompatible stem cell therapy.

Biogerontology. 2009 Aug;10(4):339-76

Authors: Nehlin JO, Barington T

Stem cell therapy based on the safe and unlimited self-renewal of human pluripotent stem cells is envisioned for future use in tissue or organ replacement after injury or disease. A gradual decline of regenerative capacity has been documented among the adult stem cell population in some body organs during the aging process. Recent progress in human somatic cell nuclear transfer and inducible pluripotent stem cell technologies has shown that patient-derived nuclei or somatic cells can be reprogrammed in vitro to become pluripotent stem cells, from which the three germ layer lineages can be generated, genetically identical to the recipient. Once differentiation protocols and culture conditions can be defined and optimized, patient-histocompatible pluripotent stem cells could be directed towards virtually every cell type in the human body. Harnessing this capability to enrich for given cells within a developmental lineage, would facilitate the transplantation of organ/tissue-specific adult stem cells or terminally differentiated somatic cells to improve the function of diseased organs or tissues in an individual. Here, we present an overview of various experimental cell therapy technologies based on the use of patient-histocompatible stem cells, the pending issues needed to be dealt with before clinical trials can be initiated, evidence for the loss and/or aging of the stem cell pool and some of the possible uses of human pluripotent stem cell-derivatives aimed at curing disease and improving health.

PMID: 19219637 [PubMed - indexed for MEDLINE]

 

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