Saturday, December 19, 2009

12/20 TE-RegenMed-StemCell feed

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Stem Cell Transplants at Childbirth.
December 19, 2009 at 7:56 am

Stem Cell Transplants at Childbirth.

Stem Cell Rev. 2009 Dec 18;

Authors: Sanberg PR, Park DH, Borlongan CV

Autologous transplantation of stem cells is a natural phenomenon at birth in mammals via the umbilical cord. Here, we discuss that a delay in the cord clamping may increase stem cell supply to the baby, thereby allowing an innate stem cell therapy that can render acute benefits in the case of neonatal disease, as well as long-term benefits against age-related diseases.

PMID: 20020331 [PubMed - as supplied by publisher]


Generation of functional hepatocytes from mouse induced pluripotent stem cells.
December 19, 2009 at 6:08 am

Generation of functional hepatocytes from mouse induced pluripotent stem cells.

J Cell Physiol. 2009 Dec 17;

Authors: Li W, Wang D, Qin J, Liu C, Zhang Q, Zhang X, Yu X, Lahn BT, Mao FF, Xiang AP

Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 20020528 [PubMed - as supplied by publisher]


Tissue engineering toward organ replacement: a promising approach in airway transplant.
December 19, 2009 at 6:08 am

Tissue engineering toward organ replacement: a promising approach in airway transplant.

Int J Artif Organs. 2009 Nov;32(11):763-8

Authors: Asnaghi A, Macchiarini P, Mantero S

Autologous tissue transfer, allografts and prosthetic replacements have so far failed to offer functional solutions for the treatment of long circumferential tracheal defects. Because of the shortcomings related with these strategies, interest has turned increasingly to the field of tissue engineering which applies the principles of engineering and life sciences in an effort to develop in vitro biological substitutes able to restore, maintain, or improve tissue and organ function. The advances in this field during the past decade have thus provided a new attractive approach toward the concept of functional substitutes and may represent an alternative to the shortage of suitable grafts for reconstructive airway surgery. This article gives an overview of the tissue engineering approach and of the encouraging strategies attempted so far in trachea regeneration.

PMID: 20020407 [PubMed - in process]


Monitoring cellular behaviour using Raman spectroscopy for tissue engineering and regenerative medicine applications.
December 19, 2009 at 6:08 am

Monitoring cellular behaviour using Raman spectroscopy for tissue engineering and regenerative medicine applications.

J Mater Sci Mater Med. 2009 Dec 18;

Authors: Boyd AR, Burke GA, Meenan BJ

Raman spectroscopy has been used to determine the chemical composition of materials for over 70 years. Recent spectacular advances in laser and CCD camera technology creating instruments with higher sensitivity and lower cost have initiated a strong resurgence in the technique, ranging from fundamental research to process control methodology. One such area of increased potential is in tissue engineering and regenerative medicine (TERM), where autologous cell culture, stem cell biology and growth of human cells on biomaterial scaffolds are of high importance. Traditional techniques for the in vitro analysis of biochemical cell processes involves cell techniques such as fixation, lysis or the use of radioactive or chemical labels which are time consuming and can involve the perpetuation of artefacts. Several studies have already shown the potential of Raman spectroscopy to provide useful information on key biochemical markers within cells, however, many of these studies have utilised micro- or confocal Raman to do this, which are not suited to the rapid and non-invasive monitoring of cells. For this study a versatile fit-for-purpose Raman spectrometer was used, employing a macro-sampling optical platform (laser spot size 100 mum at focus on the sample) to discriminate between different TERM relevant cell types and viable and non-viable cells. The results clearly show that the technique is capable of obtaining Raman spectra from live cells in a non-destructive, rapid and non-invasive manner, however, in these experiments it was not possible to discriminate between different cell lines. Despite this, notable differences were observed in the spectra obtained from viable and non-viable cells, showing significant changes in the spectral profiles of protein, DNA/RNA and lipid cell constituents after cell death. It is evident that the method employed here shows significant potential for further utilisation in TERM, providing data directly from live cells that fits within a quality assurance framework and provides the opportunity to analyse cells in a non-destructive manner.

PMID: 20020185 [PubMed - as supplied by publisher]


Porous diopside (CaMgSi(2)O(6)) scaffold: a promising bioactive material for bone tissue engineering.
December 19, 2009 at 6:08 am

Porous diopside (CaMgSi(2)O(6)) scaffold: a promising bioactive material for bone tissue engineering.

Acta Biomater. 2009 Dec 14;

Authors: Wu C, Ramaswamy Y, Zreiqat H

Diopside (CaMgSi(2)O(6)) powders and dense ceramics have been shown to be bioactive biomaterial for bone repair. The aim of this study is to prepare bioactive diopside scaffolds and examine their physicochemical and biological properties. X-ray diffraction (XRD), scanning electron microscopy (SEM), Micro-CT (mu-CT) and energy dispersive spectrometer (EDS) were used to analyse the composition, microstructure, pore size and interconnectivity of the diopside scaffolds. The mechanical strength and stability as well as the degradation of the scaffolds were investigated by testing the compressive strength, modulus and silicon (Si) ions released, respectively. Results showed that highly porous diopside scaffolds with varying porosity and high interconnectivity of 97%, were successfully prepared with improved compressive strength and mechanical stability, compared to the bioglass and CaSiO(3) scaffolds. The bioactivity of the diopside scaffolds was assessed using apatite-formation ability in simulated body fluids (SBF) and by their support to human osteoblastic-like cells (HOB) attachment, proliferation and differentiation using SEM, MTS and alkaline phosphate activity (ALP) assays, respectively. Results showed that diopside scaffolds possessed apatite-formation ability in SBF and supported HOB attachment proliferation and differentiation. Taken together, bioactive diopside scaffolds were prepared with excellent pore/structure art, improved mechanical strength and mechanical stability, suggesting their possible applications for bone tissue engineering regeneration.

PMID: 20018260 [PubMed - as supplied by publisher]


Tissue Engineering in Wound Repair: The three "R"s-Repair, Replace, Regenerate.
December 19, 2009 at 6:08 am

Tissue Engineering in Wound Repair: The three "R"s-Repair, Replace, Regenerate.

Vet Surg. 2009 Dec;38(8):905-13

Authors: Theoret C

Horses are predisposed to traumatic wounds that can be labor intensive and expensive to manage. Skin has a considerable potential for efficient and functional repair however, while cutaneous repair is a regenerative process in the fetus, this capability declines in late gestation as inflammation and scarring alter the outcome of healing. The historical gold standard for replacement of lost skin is the autologous skin graft. However, the horse's lack of redundant donor skin limits the practicality of full-thickness grafting to smaller wounds; moreover, graft failure is relatively common in equine patients as a result of infection, inflammation, fluid accumulation beneath the graft, and motion. Tissue engineering has emerged as an interdisciplinary field with the aim to regenerate new biological material for replacing diseased or damaged tissues or organs. In the case of skin, the ultimate goal is to rapidly create a construct that effects the complete regeneration of functional skin, including all its layers and appendages. Moreover, an operational vascular and nervous network, with scar-free integration within the surrounding host tissue, is desirable. For this to be achieved, not only is an appropriate source of cells required, but also a scaffold designed from natural or synthetic polymers. The newly created tissue might finally meet the numerous needs and expectations of practitioners and surgeons managing a catastrophic wound in a horse.

PMID: 20017846 [PubMed - in process]


Biomaterials for vascular tissue engineering.
December 19, 2009 at 6:08 am

Biomaterials for vascular tissue engineering.

Regen Med. 2010 Jan;5(1):107-20

Authors: Ravi S, Chaikof EL

Cardiovascular disease is the leading cause of mortality in the USA. The limited availability of healthy autologous vessels for bypass grafting procedures has led to the fabrication of prosthetic vascular conduits. While synthetic polymers have been extensively studied as substitutes in vascular engineering, they fall short of meeting the biological challenges at the blood-material interface. Various tissue engineering strategies have emerged to address these flaws and increase long-term patency of vascular grafts. Vascular cell seeding of scaffolds and the design of bioactive polymers for in situ arterial regeneration have yielded promising results. This article describes the advances made in biomaterials design to generate suitable materials that not only match the mechanical properties of native vasculature, but also promote cell growth, facilitate extracellular matrix production and inhibit thrombogenicity.

PMID: 20017698 [PubMed - in process]


Institutional Profile: McGowan Institute for Regenerative Medicine.
December 19, 2009 at 6:08 am

Institutional Profile: McGowan Institute for Regenerative Medicine.

Regen Med. 2010 Jan;5(1):23-5

Authors: Russell A

The McGowan Institute was launched in 2001 as a joint program between the University of Pittsburgh and the University of Pittsburgh Medical Center. Building from the success of the McGowan Center for Artificial Organs, the McGowan Institute employs three main pillars of research from which to accelerate research and development in regenerative medicine. It is the coalescence of these main foci - tissue engineering and biomaterials, cellular therapy, and medical devices and artificial organs - which enable McGowan to thrive in such a competitive field.

PMID: 20017691 [PubMed - in process]


Selective Nanofiber Deposition Using a Microfluidic Confinement Approach.
December 19, 2009 at 6:08 am

Selective Nanofiber Deposition Using a Microfluidic Confinement Approach.

Langmuir. 2009 Dec 17;

Authors: Yang H, Dong L

The ability to create structurally complex, accurate micropatterns in biocompatible and biodegradable nanofiber mats is important in maximally mimicking the natural extracellular matrix (ECM) for cell biology and tissue engineering. We present a simple, versatile method for the selective deposition of nanofibers with high definition using a unique microfluidic fiber collector. The collector contains fiber etching solutions that are selectively confined to defined regions by means of photocleavable self-assembled monolayer technology and microfluidic capillary filling. The presented approach achieves arbitrarily shaped, microsized, structurally accurate architectures in both random and aligned nanofibers.

PMID: 20017512 [PubMed - as supplied by publisher]


Generation of functional hepatocytes from mouse induced pluripotent stem cells.
December 19, 2009 at 6:06 am

Generation of functional hepatocytes from mouse induced pluripotent stem cells.

J Cell Physiol. 2009 Dec 17;

Authors: Li W, Wang D, Qin J, Liu C, Zhang Q, Zhang X, Yu X, Lahn BT, Mao FF, Xiang AP

Induced pluripotent stem cells are derived from somatic cells by forced expression of several transcriptional factors. Induced pluripotent stem cells resemble embryonic stem cells in many aspects, such as the expression of certain stem cell markers, chromatin methylation patterns, embryoid body formation and teratoma formation. Therefore, induced pluripotent stem cells provide a powerful tool for study of developmental biology and unlimited resources for transplantation therapy. Here we reported the successful induction of mouse induced pluripotent stem cells and a simple and efficient process for generation of functional hepatocytes from mouse induced pluripotent stem cells by sequential addition of inducing factors. These induced pluripotent stem cell-derived hepatocytes, just as mouse embryonic stem cell-derived hepatocytes, expressed hepatic lineage markers including CK7, CK8, CK18, CK19, alpha-fetoprotein, albumin, Cyp7a1, and exhibited functional hepatic characteristics, including glycogen storage, indocyanine green (ICG) uptake and release, low-density lipoprotein (LDL) uptake and urea secretion. Although we observed some variations in the efficiency of hepatic differentiation between induced pluripotent stem cells and common mouse embryonic stem cell lines, our results indicate that mouse induced pluripotent stem cells can efficiently differentiate into functional hepatocytes in vitro, which may be helpful for the study of liver development and regenerative medicine. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 20020528 [PubMed - as supplied by publisher]


Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury?
December 19, 2009 at 6:06 am

Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury?

J Cell Physiol. 2009 Dec 17;

Authors: Salewski RP, Eftekharpour E, Fehlings MG

Despite advances in medical and surgical care, current clinical therapies for spinal cord injury (SCI) are limited. During the last two decades, the search for new therapies has been revolutionized by the discovery of stem cells, inspiring scientists and clinicians to search for stem cell-based reparative approaches for many disorders, including neurotrauma. Cell-based therapies using embryonic and adult stem cells in animal models of these disorders have provided positive outcome results. However, the availability of clinically suitable cell sources for human application has been hindered by both technical and ethical issues. The recent discovery of induced pluripotent stem (iPS) cells holds the potential to revolutionize the field of regenerative medicine by offering the option of autologous transplantation, thus eliminating the issue of host rejection. Herein, we will provide the rationale for the use of iPS cells in SCI therapies. In this review, we will evaluate the recent advancements in the field of iPS cells including their capacity for differentiation toward neural lineages that may allow iPS cells transplantation in cell-based therapy for spinal cord repair. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 20020443 [PubMed - as supplied by publisher]


Monitoring cellular behaviour using Raman spectroscopy for tissue engineering and regenerative medicine applications.
December 19, 2009 at 6:06 am

Monitoring cellular behaviour using Raman spectroscopy for tissue engineering and regenerative medicine applications.

J Mater Sci Mater Med. 2009 Dec 18;

Authors: Boyd AR, Burke GA, Meenan BJ

Raman spectroscopy has been used to determine the chemical composition of materials for over 70 years. Recent spectacular advances in laser and CCD camera technology creating instruments with higher sensitivity and lower cost have initiated a strong resurgence in the technique, ranging from fundamental research to process control methodology. One such area of increased potential is in tissue engineering and regenerative medicine (TERM), where autologous cell culture, stem cell biology and growth of human cells on biomaterial scaffolds are of high importance. Traditional techniques for the in vitro analysis of biochemical cell processes involves cell techniques such as fixation, lysis or the use of radioactive or chemical labels which are time consuming and can involve the perpetuation of artefacts. Several studies have already shown the potential of Raman spectroscopy to provide useful information on key biochemical markers within cells, however, many of these studies have utilised micro- or confocal Raman to do this, which are not suited to the rapid and non-invasive monitoring of cells. For this study a versatile fit-for-purpose Raman spectrometer was used, employing a macro-sampling optical platform (laser spot size 100 mum at focus on the sample) to discriminate between different TERM relevant cell types and viable and non-viable cells. The results clearly show that the technique is capable of obtaining Raman spectra from live cells in a non-destructive, rapid and non-invasive manner, however, in these experiments it was not possible to discriminate between different cell lines. Despite this, notable differences were observed in the spectra obtained from viable and non-viable cells, showing significant changes in the spectral profiles of protein, DNA/RNA and lipid cell constituents after cell death. It is evident that the method employed here shows significant potential for further utilisation in TERM, providing data directly from live cells that fits within a quality assurance framework and provides the opportunity to analyse cells in a non-destructive manner.

PMID: 20020185 [PubMed - as supplied by publisher]


Application of Drag-Reducing Polymer Solutions as Test Fluids for In Vitro Evaluation of Potential Blood Damage in Blood Pumps.
December 19, 2009 at 6:06 am

Application of Drag-Reducing Polymer Solutions as Test Fluids for In Vitro Evaluation of Potential Blood Damage in Blood Pumps.

ASAIO J. 2009 Dec 16;

Authors: Daly AR, Sobajima H, Olia SE, Takatani S, Kameneva MV

In vitro evaluation of the potential of a circulatory-assist device to damage blood cells has generally been performed using blood from various species. Problems with this approach include the variability of blood sensitivity to mechanical stress in different species, preparation of blood including the adjustment of hematocrit to a standard value, changes in the mechanical properties of blood that occur during storage, and necessity to pool blood samples to obtain an adequate amount of blood for In vitro circulating systems. We investigated whether the mechanical degradation of a drag-reducing polymer (DRP) solution resulting in the loss of drag-reducing ability can indicate the degree of shear-induced blood damage within blood pumps. DRP solution (polyethylene oxide, 4,500 kDa, 1,000 ppm) or porcine blood were driven through a turbulent flow system by a centrifugal pump, either the Bio-Pump BPX-80 (Medtronic, Inc.) or CentriMag (Levitronix LLC) at a constant pressure gradient of 300 mm Hg for 120 minutes. DRP mechanical degradation was evaluated by reduction of flow rate and solution viscosity. A proposed index of DRP mechanical degradation (PDI) is similar to the normalized index of hemolysis (NIH) typically used to quantify the results of In vitro testing of blood pumps. Results indicate that the mechanical degradation of DRP solutions may provide a sensitive standard method for the evaluation of potential blood trauma produced by blood pumps without the use of blood.

PMID: 20019596 [PubMed - as supplied by publisher]


Liver Regeneration after Partial Hepatectomy. Critical Analysis of Mechanistic Dilemmas.
December 19, 2009 at 6:06 am

Liver Regeneration after Partial Hepatectomy. Critical Analysis of Mechanistic Dilemmas.

Am J Pathol. 2009 Dec 17;

Authors: Michalopoulos GK

Liver regeneration after partial hepatectomy is one of the most studied models of cell, organ, and tissue regeneration. The complexity of the signaling pathways initiating and terminating this process have provided paradigms for regenerative medicine. Many aspects of the signaling mechanisms involved in hepatic regeneration are under active investigation. The purpose of this review is to focus on the areas still not well understood. The review also aims to provide insights into the ways by which current concepts of liver regeneration can provide understanding regarding malfunction of the regenerative process in liver diseases, such as acute liver failure.

PMID: 20019184 [PubMed - as supplied by publisher]


Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas.
December 19, 2009 at 6:06 am

Isolation and characterization of centroacinar/terminal ductal progenitor cells in adult mouse pancreas.

Proc Natl Acad Sci U S A. 2009 Dec 15;

Authors: Rovira M, Scott SG, Liss AS, Jensen J, Thayer SP, Leach SD

The question of whether dedicated progenitor cells exist in adult vertebrate pancreas remains controversial. Centroacinar cells and terminal duct (CA/TD) cells lie at the junction between peripheral acinar cells and the adjacent ductal epithelium, and are frequently included among cell types proposed as candidate pancreatic progenitors. However these cells have not previously been isolated in a manner that allows formal assessment of their progenitor capacities. We have found that a subset of adult CA/TD cells are characterized by high levels of ALDH1 enzymatic activity, related to high-level expression of both Aldh1a1 and Aldh1a7. This allows their isolation by FACS using a fluorogenic ALDH1 substrate. FACS-isolated CA/TD cells are relatively depleted of transcripts associated with differentiated pancreatic cell types. In contrast, they are markedly enriched for transcripts encoding Sca1, Sdf1, c-Met, Nestin, and Sox9, markers previously associated with progenitor populations in embryonic pancreas and other tissues. FACS-sorted CA/TD cells are uniquely able to form self-renewing "pancreatospheres" in suspension culture, even when plated at clonal density. These spheres display a capacity for spontaneous endocrine and exocrine differentiation, as well as glucose-responsive insulin secretion. In addition, when injected into cultured embryonic dorsal pancreatic buds, these adult cells display a unique capacity to contribute to both the embryonic endocrine and exocrine lineages. Finally, these cells demonstrate dramatic expansion in the setting of chronic epithelial injury. These findings suggest that CA/TD cells are indeed capable of progenitor function and may contribute to the maintenance of tissue homeostasis in adult mouse pancreas.

PMID: 20018761 [PubMed - as supplied by publisher]


Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: Current impact and future directions.
December 19, 2009 at 6:06 am

Regenerative stromal cell therapy in allogeneic hematopoietic stem cell transplantation: Current impact and future directions.

Biol Blood Marrow Transplant. 2009 Dec 14;

Authors: Auletta JJ, Cooke KR, Solchaga LA, Deans RJ, Van't Hof W

Regenerative stromal cell therapy (RSCT) has the potential to become a novel therapy for preventing and treating acute graft-versus-host disease (GVHD) in the allogeneic hematopoietic stem cell transplant (HSCT) recipient. However, enthusiasm for using RSCT in allogeneic HSCT has been tempered by limited clinical data and poorly-defined in vivo mechanisms of action. As a result, the full clinical potential of RSCT in supporting hematopoietic reconstitution and as treatment for GVHD remains to be determined. This manuscript reviews the immunomodulatory activity of regenerative stromal cells in pre-clinical models of allogeneic HSCT and emphasizes an emerging literature suggesting that microenvironment influences RSC activation and function. Understanding this key finding may ultimately define the proper niche for RSCT in allogeneic HSCT. In particular, mechanistic studies are needed to delineate the in vivo effects of RSCT in response to inflammation and injury associated with allogeneic HSCT and to define the relevant sites of RSC interaction with immune cells in the transplant recipient. Furthermore, development of in vivo imaging technology to correlate biodistribution patterns, desired RSC effect, and clinical outcome will be crucial to establishing dose-response effects and minimal biologic-dose thresholds needed to advance translational treatment strategies for complications like GVHD.

PMID: 20018250 [PubMed - as supplied by publisher]


Erratum.
December 19, 2009 at 6:06 am

Erratum.

Regen Med. 2010 Jan;5(1):151-2

Authors:

PMID: 20017702 [PubMed - in process]


Corrigendum.
December 19, 2009 at 6:06 am

Corrigendum.

Regen Med. 2010 Jan;5(1):150

Authors:

PMID: 20017701 [PubMed - in process]


Acknowledgements.
December 19, 2009 at 6:06 am

Acknowledgements.

Regen Med. 2010 Jan;5(1):148

Authors:

PMID: 20017700 [PubMed - in process]


Stem cell paracrine actions and tissue regeneration.
December 19, 2009 at 6:06 am

Stem cell paracrine actions and tissue regeneration.

Regen Med. 2010 Jan;5(1):121-43

Authors: Baraniak PR, McDevitt TC

Stem cells have emerged as a key element of regenerative medicine therapies due to their inherent ability to differentiate into a variety of cell phenotypes, thereby providing numerous potential cell therapies to treat an array of degenerative diseases and traumatic injuries. A recent paradigm shift has emerged suggesting that the beneficial effects of stem cells may not be restricted to cell restoration alone, but also due to their transient paracrine actions. Stem cells can secrete potent combinations of trophic factors that modulate the molecular composition of the environment to evoke responses from resident cells. Based on this new insight, current research directions include efforts to elucidate, augment and harness stem cell paracrine mechanisms for tissue regeneration. This article discusses the existing studies on stem/progenitor cell trophic factor production, implications for tissue regeneration and cancer therapies, and development of novel strategies to use stem cell paracrine delivery for regenerative medicine.

PMID: 20017699 [PubMed - in process]

 

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