Wednesday, November 4, 2009

11/5 pubmed: "regenerative medici...

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A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response.
November 4, 2009 at 6:27 am

A Review of the Biocompatibility of Implantable Devices: Current Challenges to Overcome Foreign Body Response.

J Diabetes Sci Technol. 2008 Nov;2(6):1003-1015

Authors: Onuki Y, Bhardwaj U, Papadimitrakopoulos F, Burgess DJ

In recent years, a variety of devices (drug-eluting stents, artificial organs, biosensors, catheters, scaffolds for tissue engineering, heart valves, etc.) have been developed for implantation into patients. However, when such devices are implanted into the body, the body can react to these in a number of different ways. These reactions can result in an unexpected risk for patients. Therefore, it is important to assess and optimize the biocompatibility of implantable devices. To date, numerous strategies have been investigated to overcome body reactions induced by the implantation of devices. This review focuses on the foreign body response and the approaches that have been taken to overcome this. The biological response following device implantation and the methods for biocompatibility evaluation are summarized. Then the risks of implantable devices and the challenges to overcome these problems are introduced. Specifically, the challenges used to overcome the functional loss of glucose sensors, restenosis after stent implantation, and calcification induced by implantable devices are discussed.

PMID: 19885290 [PubMed - as supplied by publisher]


Stem cells in gastroenterology and hepatology.
November 4, 2009 at 6:27 am

Stem cells in gastroenterology and hepatology.

Nat Rev Gastroenterol Hepatol. 2009 Nov 3;

Authors: Quante M, Wang TC

Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use of stem cells in regenerative medicine and treatments for disease. Embryonic stem cells and induced pluripotent stem cells have the potential to give rise to any cell type in the human body, but their therapeutic application remains challenging. The use of adult or tissue-restricted stem cells is emerging as another possible approach for the treatment of gastrointestinal diseases. The same self-renewal properties that allow stem cells to remain immortal and generate any tissue can occasionally make their proliferation difficult to control and make them susceptible to malignant transformation. This Review provides an overview of the different types of stem cell, focusing on tissue-restricted adult stem cells in the fields of gastroenterology and hepatology and summarizing the potential benefits and risks of using stems cells to treat gastroenterological and liver disorders.

PMID: 19884893 [PubMed - as supplied by publisher]


Regenerative Medicine Special Feature: Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury.
November 4, 2009 at 6:27 am

Regenerative Medicine Special Feature: Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury.

Proc Natl Acad Sci U S A. 2009 Nov 2;

Authors: Lee H, McKeon RJ, Bellamkonda RV

Chondroitin sulfate proteoglycans (CSPGs) are a major class of axon growth inhibitors that are up-regulated after spinal cord injury (SCI) and contribute to regenerative failure. Chondroitinase ABC (chABC) digests glycosaminoglycan chains on CSPGs and can thereby overcome CSPG-mediated inhibition. But chABC loses its enzymatic activity rapidly at 37 degrees C, necessitating the use of repeated injections or local infusions for a period of days to weeks. These infusion systems are invasive, infection-prone, and clinically problematic. To overcome this limitation, we have thermostabilized chABC and developed a system for its sustained local delivery in vivo, obviating the need for chronically implanted catheters and pumps. Thermostabilized chABC remained active at 37 degrees C in vitro for up to 4 weeks. CSPG levels remained low in vivo up to 6 weeks post-SCI when thermostabilized chABC was delivered by a hydrogel-microtube scaffold system. Axonal growth and functional recovery following the sustained local release of thermostabilized chABC versus a single treatment of unstabilized chABC demonstrated significant differences in CSPG digestion. Animals treated with thermostabilized chABC in combination with sustained neurotrophin-3 delivery showed significant improvement in locomotor function and enhanced growth of cholera toxin B subunit-positive sensory axons and sprouting of serotonergic fibers. Therefore, improving chABC thermostability facilitates minimally invasive, sustained, local delivery of chABC that is potentially effective in overcoming CSPG-mediated regenerative failure. Combination therapy with thermostabilized chABC with neurotrophic factors enhances axonal regrowth, sprouting, and functional recovery after SCI.

PMID: 19884507 [PubMed - as supplied by publisher]


What's New in Orthopaedic Research.
November 4, 2009 at 6:27 am

What's New in Orthopaedic Research.

J Bone Joint Surg Am. 2009 Nov;91-A(11):2756-2770

Authors: Hidaka C, Maher S, Packer J, Gasinu S, Cunningham ME, Rodeo S

PMID: 19884457 [PubMed - as supplied by publisher]


Commitment of stem cells into functional hepatocytes.
November 4, 2009 at 6:27 am

Commitment of stem cells into functional hepatocytes.

Differentiation. 2009 Oct 31;

Authors: Ochiya T, Yamamoto Y, Banas A

Liver transplants represent the only way to treat patients suffering from terminal liver failure, but they are associated with numerous problems, including a chronic shortage of donors, high cost, rejection, and side effects for the donor. It is anticipated that regenerative medicine will provide an alternative to liver transplants for such patients. Regenerative medicine refers to the academic field of eliciting the inherent capacity of organisms for self-regeneration to the greatest possible extent in order to develop new methods of treatment for intractable disorders. From this perspective, much is expected from the use of human embryonic stem cells (ES cells) or induced pluripotent stem cells (iPS cells), and the vigorous development of technology to induce the differentiation of such stem cells into cells possessing hepatic functions is underway. Clinical applications of these human stem cells, however, have yet to reach even the earliest stages of implementation. Facing off against these versatile ES cells are stem cells derived from somatic cells present within organisms, which are attracting attention owing to their superiority in terms of ethics and safety, with many research institutes now in the process of elucidating the details of stem cell separation and identification as well as their plasticity and pluripotency. Bone marrow cells are the best-known somatic-cell-derived stem cells, but the use of mesenchymal stem cells (MSCs) found in adipose tissue has also recently attracted attention. This paper will review the differentiation ability and mechanisms of these various stem cell types to hepatocytes and their application to liver regeneration and the future outlook.

PMID: 19883970 [PubMed - as supplied by publisher]


Endothelial Differentiation of Adipose-Derived Stem Cells: Effects of Endothelial Cell Growth Supplement and Shear Force.
November 4, 2009 at 6:27 am

Endothelial Differentiation of Adipose-Derived Stem Cells: Effects of Endothelial Cell Growth Supplement and Shear Force.

J Surg Res. 2009 Mar;152(1):157-166

Authors: Fischer LJ, McIlhenny S, Tulenko T, Golesorkhi N, Zhang P, Larson R, Lombardi J, Shapiro I, Dimuzio PJ

BACKGROUND: Adipose tissue is a readily available source of multipotent adult stem cells for use in tissue engineering/regenerative medicine. Various growth factors have been used to stimulate acquisition of endothelial characteristics by adipose-derived stem cells (ASC). Herein we study the effects of endothelial cell growth supplement (ECGS) and physiological shear force on the differentiation of ASC into endothelial cells. MATERIALS AND METHODS: Human ASC (CD13(+)29(+)90(+)31(-)45(-)) were isolated from periumbilical fat, cultured in ECGS media (for up to 3 wk), and exposed to physiological shear force (12 dynes for up to 8 d) in vitro. Endothelial phenotype was defined by cord formation on Matrigel, acetylated-low density lipoprotein (acLDL) uptake, and expression of nitric oxide synthase (eNOS), von Willebrand factor (vWF), and CD31 (platelet endothelial cell adhesion molecule, PECAM). Additionally, cell thrombogenicity was evaluated by seeding canine autologous ASC onto vascular grafts implanted within the canine arterial circulation for 2 wk. RESULTS: We found that undifferentiated ASC did not display any of the noted endothelial characteristics. After culture in ECGS, ASC formed cords in Matrigel but failed to take up acLDL or express the molecular markers. Subsequent exposure to shear resulted in stem cell realignment, acLDL uptake, and expression of CD31; eNOS and vWF expression was still not observed. Grafts seeded with cells grown in ECGS (+/- shear) remained patent (six of seven) at 2 wk but had a thin coat of fibrin along the luminal surfaces. CONCLUSIONS: This study suggests that (1) ECGS and shear promote the expression of several endothelial characteristics in human adipose-derived stem cells, but not eNOS or vWF; (2) their combined effects appear synergistic; and (3) stem cells differentiated in ECGS appear mildly thrombogenic in vitro, possibly related, in part, to insufficient eNOS expression. Thus, while the acquisition of several endothelial characteristics by adult stem cells derived from adipose tissue suggests these cells are a viable source of autologous cells for cardiovascular regeneration, further stimulation/modifications are necessary prior to using them as a true endothelial cell replacement.

PMID: 19883577 [PubMed - as supplied by publisher]


Laser Printing of Skin Cells and Human Stem Cells.
November 4, 2009 at 6:27 am

Laser Printing of Skin Cells and Human Stem Cells.

Tissue Eng Part C Methods. 2009 Nov 2;

Authors: Koch L, Kuhn S, Sorg H, Gruene M, Schlie S, Gaebel R, Polchow B, Reimers K, Stoelting S, Ma N, Vogt P, Steinhoff G, Chichkov BN

Laser printing based on laser-induced forward transfer (LIFT) is a new biofabrication technique for the arrangement of biological materials or living cells in well-defined patterns. In the current study, skin cell lines (fibroblasts/keratinocytes) and human mesenchymal stem cells (hMSC) were chosen for laser printing experiments due to their high potential in regeneration of human skin and new application possibilities of stem cell therapy. To evaluate the influence of LIFT on the cells, their survival rate, their proliferation and apoptotic activity, as well as DNA damages and modifications of their cell surface markers, were assessed and statistically evaluated over several days. The cells survived the transfer procedure with a rate of 98% +/- 1% SEM (skin cells) and 90% +/- 10% (hMSC), respectively. All used cell types maintain their ability to proliferate after LIFT. Furthermore, skin cells and hMSC did not show an increase of apoptosis or DNA fragmentation. In addition, the hMSC keep their phenotype as proven by FACS analysis. This study demonstrates LIFT as a suitable technique for unharmed computer-controlled positioning of different cell types and a promising tool for future applications in the ex vivo generation of tissue replacements.

PMID: 19883209 [PubMed - as supplied by publisher]


[Stem cell therapy: an update]
November 4, 2009 at 6:27 am

[Stem cell therapy: an update]

Bull Acad Natl Med. 2009 Mar;193(3):535-6

Authors: Coulombel L

Medicine will be faced with a major challenge in coming years, namely how to treat for tissue dysfunction due to disease and aging There are two basic options: drug therapy and cell therapy. Stem cells have been the subject of intense speculation and controversy for several years, as they open up radically new therapeutic possibilities. Classical drugs can only smoothen consequences of tissue dysfunction, whereas cell therapy has the potential to restore tissue function by providing fresh cells. Cell therapy is totally different from organ transplantation, which can only benefit a limited number of patients. The use of the generic term "stem cells" to designate a whole variety of cell types that are present throughout life, is a source of confusion and ambiguity. It will take years of cognitive research to unravel the molecular mechanisms that govern a stem cell's multi- or totipotent status before we can fully exploit this therapeutic tool to the full. The younger a stem cell the greater its potential and, probably, the more durable its benefits, but the use of embryonic stem cells raises ethical issues. The redundancy or equivalence of diferent categories of cells is another source of controversy, yet researchers must be able to study stem cells in all their diversity, as complementary rather than competitive alternatives, in an acceptable ethical and regulatory environment. We briefly describe the three types of stem cells: pluripotent embryonic stem cells, fetal and adult stem cells, and pluripotent reprogrammed adult somatic cells. Only the former two categories have physiological functions: the first gives rise to tissues and organs while the second maintains tissue function during adulthood

PMID: 19883007 [PubMed - in process]

 

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