Wednesday, March 10, 2010

3/11 pubmed: "regenerative medici...

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SnapShot: Bioreactors systems in tissue engineering (TE) & regenerative medicine (RM).
March 10, 2010 at 6:32 AM

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SnapShot: Bioreactors systems in tissue engineering (TE) & regenerative medicine (RM).

Biomaterials. 2010 Apr;31(11):3114-5

Authors: Martin I, Riboldi SA, Jakob M, Wendt D

PMID: 20213922 [PubMed - in process]

 

Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: From fabrication to preclinical validation.
March 10, 2010 at 6:32 AM

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Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: From fabrication to preclinical validation.

J Biomed Mater Res A. 2010 Mar 8;

Authors: Mondalek FG, Ashley RA, Roth CC, Kibar Y, Shakir N, Ihnat MA, Fung KM, Grady BP, Kropp BP, Lin HK

Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane angiogenesis model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-! PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

PMID: 20213816 [PubMed - as supplied by publisher]

 

Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.
March 10, 2010 at 6:32 AM

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Microsphere size effects on embryoid body incorporation and embryonic stem cell differentiation.

J Biomed Mater Res A. 2010 Mar 8;

Authors: Carpenedo RL, Seaman SA, McDevitt TC

Differentiation of pluripotent embryonic stem cells (ESCs) in vitro via multicellular spheroids called embryoid bodies (EBs) is commonly performed to model aspects of early mammalian development and initiate differentiation of cells for regenerative medicine technologies. However, the three-dimensional nature of EBs poses unique challenges for directed ESC differentiation, including limited diffusion into EBs of morphogenic molecules capable of specifying cell fate. Degradable polymer microspheres incorporated within EBs can present morphogenic molecules to ESCs in a spatiotemporally controlled manner to more efficiently direct differentiation. In this study, the effect of microsphere size on incorporation into EBs and ESC differentiation in response to microsphere- mediated morphogen delivery were assessed. PLGA microspheres with mean diameters of 1, 3, or 11 mum were fabricated and mixed with ESCs during EB formation. Smaller microspheres were incorporated more ! efficiently throughout EBs than larger microspheres, and regardless of size, retained for at least 10 days of differentiation. Retinoic acid release from incorporated microspheres induced EB cavitation in a size-dependent manner, with smaller microspheres triggering accelerated and more complete cavitation than larger particles. These results demonstrate that engineering the size of microsphere delivery vehicles incorporated within stem cell environments can be used to modulate the course of differentiation. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

PMID: 20213812 [PubMed - as supplied by publisher]

 

Biocompatibility of synthetic poly(ester urethane)/polyhedral oligomeric silsesquioxane matrices with embryonic stem cell proliferation and differentiation.
March 10, 2010 at 6:32 AM

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Biocompatibility of synthetic poly(ester urethane)/polyhedral oligomeric silsesquioxane matrices with embryonic stem cell proliferation and differentiation.

J Tissue Eng Regen Med. 2010 Mar 8;

Authors: Guo YL, Wang W, Otaigbe JU

Incorporation of polyhedral oligomeric silsesquioxanes (POSS) into poly(ester urethanes) (PEU) as a building block results in a PEU/POSS hybrid polymer with increased mechanical strength and thermostability. An attractive feature of the new polymer is that it forms a porous matrix when cast in the form of a thin film, making it potentially useful in tissue engineering. In this study, we present detailed microscopic analysis of the PEU/POSS matrix and demonstrate its biocompatibility with cell culture. The PEU/POSS polymer forms a continuous porous matrix with open pores and interconnected grooves. From SEM image analysis, it is calculated that there are about 950 pores/mm(2) of the matrix area with pore diameter size in the range 1-15 microm. The area occupied by the pores represents approximately 7.6% of the matrix area. Using mouse embryonic stem cells (ESCs), we demonstrate that the PEU/POSS matrix provides excellent support for cell proliferation and different! iation. Under the cell culture condition optimized to maintain self-renewal, ESCs grown on a PEU/POSS matrix exhibit undifferentiated morphology, express pluripotency markers and have a similar growth rate to cells grown on gelatin. When induced for differentiation, ESCs underwent dramatic morphological change, characterized by the loss of clonogenecity and increased cell size, with well-expanded cytoskeleton networks. Differentiated cells are able to form a continuous monolayer that is closely embedded in the matrix. The excellent compatibility between the PEU/POSS matrix and ESC proliferation/differentiation demonstrates the potential of using PEU/POSS polymers in future ESC-based tissue engineering. Copyright (c) 2010 John Wiley & Sons, Ltd.

PMID: 20213627 [PubMed - as supplied by publisher]

 

Prominin-1: a distinct cholesterol-binding membrane protein and the organisation of the apical plasma membrane of epithelial cells.
March 10, 2010 at 6:32 AM

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Prominin-1: a distinct cholesterol-binding membrane protein and the organisation of the apical plasma membrane of epithelial cells.

Subcell Biochem. 2010;51:399-423

Authors: Corbeil D, Marzesco AM, Fargeas CA, Huttner WB

The apical plasma membrane of polarized epithelial cells is composed of distinct subdomains, that is, planar regions and protrusions (microvilli, primary cilium), each of which are constructed from specific membrane microdomains. Assemblies containing the pentaspan glycoprotein prominin-1 and certain membrane lipids, notably cholesterol, are characteristic features of these microdomains in apical membrane protrusions. Here we highlight the recent findings concerning the molecular architecture of the apical plasma membrane of epithelial cells and its dynamics. The latter is illustrated by the budding and fission of prominin-1-containing membrane vesicles from apical plasma membrane protrusions, which is controlled, at least in part, by the level of membrane cholesterol and the cholesterol-dependent organization of membrane microdomains.

PMID: 20213552 [PubMed - in process]

 

Does ciprofloxacin have an obverse and a reverse?
March 10, 2010 at 6:32 AM

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Does ciprofloxacin have an obverse and a reverse?

Pulm Pharmacol Ther. 2010 Mar 4;

Authors: Kloskowski T, Gurtowska N, Drewa T

Ciprofloxacin is an antibiotic that belongs to fluoroquinoles, characterized by broad spectrum of action against pathogens, especially Gram(-) aerobic bacilli. For a long time, it has been thought that ciprofloxacin has an effect only on bacterial cells. Now it is known, that this drug can significantly affect eukaryotic cells including human cancer cells. Its bactericidal action relay on inhibition of topoisomerase II, enzyme responsible for alterations in 3D structure of DNA during replication, transcription and chromatin condensation. Thanks to that, ciprofloxacin can induce cell cycle arrest and apoptosis of cancer cells. The effectiveness of ciprofloxacin was confirmed in several in vitro studies on tumor cell lines such as: human bladder cells, leukaemic cell lines, human osteosarcoma cells, human prostate cancer cells, human colorectal carcinoma cells and human non-small cell lung cancer cell line. Ciprofloxacin is particularly effective against non-small c! ell lung cancer mainly due to accumulation of ciprofloxacin in lung tissue after intravenous administration and its toxicity against lung cancer lines in vitro in a concentration and time dependent manner.

PMID: 20211752 [PubMed - as supplied by publisher]

 

Bone Morphogenetic Proteins And Articular Cartilage To serve and protect or a wolf in sheep clothing's?
March 10, 2010 at 6:32 AM

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Bone Morphogenetic Proteins And Articular Cartilage To serve and protect or a wolf in sheep clothing's?

Osteoarthritis Cartilage. 2010 Mar 4;

Authors: van der Kraan PM, Davidson EN, van den Berg WB

OBJECTIVE: Alterations in chondrocyte differentiation and matrix remodeling play a central role in osteoarthritis. Chondrocyte differentiation and remodeling is amongst others regulated by the so-called Bone Morphogenetic Proteins (BMPs). Although BMPs are considered protective for articular cartilage these factors can also be involved in chondrocyte hypertrophy and matrix degradation. This review is focused on these opposed roles of BMPs in osteoarthritis (OA) development and progression. METHODS: Peer reviewed publications published prior to August 2009 were searched in the Pubmed database. Articles that were relevant for the role of endogenous BMPs in OA were selected. Since good quality reviews on the application of BMP supplementation in cartilage tissue engineering have been described this subject has not been covered in this review. RESULTS: BMPs can stimulate both chondrocyte matrix synthesis and chondrocyte terminal differentiation. The latter results in ! elevated MMP13 production. Stimulation of matrix synthesis will be protective for cartilage while elevated MMP13 activity will drive matrix degradation. What action of BMPs is dominant in OA is not yet elucidated and their role might different in patient subgroups. CONCLUSION: BMPs can be protective for articular cartilage but can, due to their effect on chondrocyte differentiation, have harmful effects on articular cartilage and contribute to OA progression.

PMID: 20211748 [PubMed - as supplied by publisher]

 

Editorial comment.
March 10, 2010 at 6:32 AM

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Editorial comment.

Urology. 2010 Mar;75(3):670

Authors: Atala A

PMID: 20211376 [PubMed - in process]

 

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction.
March 10, 2010 at 6:32 AM

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Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction.

Am J Cardiol. 2010 Mar 15;105(6):804-812

Authors: Wöhrle J, Merkle N, Mailänder V, Nusser T, Schauwecker P, von Scheidt F, Schwarz K, Bommer M, Wiesneth M, Schrezenmeier H, Hombach V

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42! patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

PMID: 20211323 [PubMed - as supplied by publisher]

 

Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture.
March 10, 2010 at 6:32 AM

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Bio-printing of collagen and VEGF-releasing fibrin gel scaffolds for neural stem cell culture.

Exp Neurol. 2010 Mar 5;

Authors: Lee YB, Polio S, Lee W, Dai G, Menon L, Carroll RS, Yoo SS

Time-released delivery of soluble growth factors (GFs) in engineered hydrogel tissue constructs promotes the migration and proliferation of embedded cells, which is an important factor for designing scaffolds that ultimately aim for neural tissue regeneration. We report a tissue engineering technique to print murine neural stem cells (C17.2), collagen hydrogel, and GF (vascular endothelial growth factor: VEGF)-releasing fibrin gel to construct an artificial neural tissue. We examined the morphological changes of the printed C17.2 cells embedded in the collagen and its migration toward the fibrin gel. The cells showed high viability (92.89+/-2.32%) after printing, which was equivalent to that of manually-plated cells. C17.2 cells printed within 1mm from the border of VEGF-releasing fibrin gel showed GF-induced changes in their morphology. The cells printed in this range also migrated toward the fibrin gel, with the total migration distance of 102.4+/-76.1microm ove! r 3days. The cells in the control samples (fibrin without the VEGF or VEGF printed directly in collagen) neither proliferated nor migrated. The results demonstrated that bio-printing of VEGF-containing fibrin gel supported sustained release of the GF in the collagen scaffold. The presented method can be gainfully used in the development of three-dimensional (3D) artificial tissue assays and neural tissue regeneration applications.

PMID: 20211178 [PubMed - as supplied by publisher]

 

Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells.
March 10, 2010 at 6:32 AM

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Portal venous endothelium in developing human liver contains haematopoietic and epithelial progenitor cells.

Exp Cell Res. 2010 Mar 5;

Authors: Terrace JD, Hay DC, Samuel K, Anderson RA, Currie IS, Parks RW, Forbes SJ, Ross JA

Future treatments for chronic liver disease are likely to involve manipulation of liver progenitor cells (LPCs). In the human, data characterising the regenerative response is limited and the origin of adult LPCs is unknown. However, these remain critical factors in the design of cell-based liver therapies. The developing human liver provides an ideal model to study cell lineage derivation from progenitors and to understand how foetal haematopoiesis and liver development might explain the nature of the adult LPC population. In 1st trimester human liver, portal venous endothelium (PVE) expressed adult LPC markers and markers of haematopoietic progenitor cells (HPCs) shared with haemogenic endothelium found in the embryonic dorsal aorta. Sorted PVE cells were able to generate hepatoblast-like cells co-expressing CK18 and CK19 in addition to Dlk/pref-1, E-cadherin, albumin and fibrinogen in vitro. Furthermore, PVE cells could initiate haematopoiesis. These data sugge! st that PVE shares phenotypical and functional similarities both with adult LPCs and embryonic haemogenic endothelium. This indicates that a temporal relationship might exist between progenitor cells in foetal liver development and adult liver regeneration, which may involve progeny of PVE.

PMID: 20211168 [PubMed - as supplied by publisher]

 

FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures.
March 10, 2010 at 6:32 AM

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FGF but not EGF induces phosphorylation of the cAMP response element binding protein in olfactory mucosa-derived cell cultures.

Exp Cell Res. 2010 Mar 5;

Authors: Barraud P, He X, Zhao C, Caldwell MA, Franklin RJ

The stem/progenitor cells of the olfactory epithelium are potentially useful cells for autologous cell-based therapy because of their relative accessibility compared to other sources of neural stem cells. However, they have very limited potential to self-renew in vitro under growth factor stimulation compared to central nervous system-derived stem/progenitor cells. Using a sphere-forming assay and immunocytochemistry to identify cells that contained phosphorylated cAMP response element binding protein (pCREB) as an indicator of cell responsiveness to growth factor activation, we found that olfactory-spheres primed with FGF2 responded to FGF2 and EGF stimulation. In contrast, olfactory-spheres primed with EGF failed to respond to FGF2 or EGF stimulation despite the detection of FGFR1 and EGFR and their transcripts. These data demonstrate that FGF2 but not EGF permit the maintenance of a subset of cells responsive to FGF2 and EGF whereas EGF induces unresponsive to ! either growth factor possibly via intrinsic mechanisms of regulation.

PMID: 20211167 [PubMed - as supplied by publisher]

 

Regulation of cell shape, wing hair initiation and the actin cytoskeleton by Trc/Fry and Wts/Mats complexes.
March 10, 2010 at 6:32 AM

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Regulation of cell shape, wing hair initiation and the actin cytoskeleton by Trc/Fry and Wts/Mats complexes.

Dev Biol. 2010 Mar 5;

Authors: Fang X, Adler PN

The two NDR kinase family genes in Drosophila are tricornered (trc) and warts (wts). Previous studies on trc have focused on its role in the morphogenesis of extensions of epidermal cells and in dendrite branching and tiling. Studies on wts have focused on its roles as a tumor suppressor, in controlling photoreceptor type and in the maintenance of dendrites. Here we examine and compare the function of these genes in wing cells prior to their terminal differentiation. Mutations in these genes lead to changes in cell shape, cellular levels of F-actin, the timing of differentiation, and the expression of multiple wing hairs and DE-Cadherin. We showed that the effects of wts on all of these processes appear to be mediated by its regulation of the Yorkie transcription factor. We also provide evidence that trc regulates the expression of DE-cadherin and mwh. In addition, we showed that the effects on cell shape and the timing of differentiation appear to not be linked t! o changes in relative growth rate of cells compared to their neighbors.

PMID: 20211163 [PubMed - as supplied by publisher]

 

Acknowledgements.
March 10, 2010 at 6:32 AM

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Acknowledgements.

Regen Med. 2010 Mar;5(2):305

Authors:

PMID: 20210589 [PubMed - in process]

 

In vitro human bone marrow analog: clinical potential.
March 10, 2010 at 6:32 AM

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In vitro human bone marrow analog: clinical potential.

Regen Med. 2010 Mar;5(2):289-98

Authors: Nichols JE, Niles J, Walls S, Cortiella J

Bone marrow is the primary site of hematopoiesis in adult humans. Bone marrow can be cultured in vitro but few simple culture systems fully support hematopoiesis beyond a few months. Human bone marrow analogs are long-term in vitro cultures of marrow stromal and hematopoietic stem cells that can be used to produce cells and products normally harvested from human donors. Bone marrow analog systems should exhibit confluence of the stromal cell populations, persistence of hematopoietic progenitor cells, presence of active regions of hematopoiesis and capacity to produce mature cell types for extended periods of time. Although we are still years away from realizing clinical application of products formed by artificial bone marrow analogs, the process of transitioning this research tool from bench to bedside should be fairly straightforward. The most obvious application of artificial marrow would be for production of autologous hematopoietic CD34(+) stem cells as a ste! m cell therapy for individuals experiencing bone marrow failure due to disease or injury. Another logical application is for 'blood farming', a process for large-scale in vitro production of red blood cells, white blood cells or platelets, for transfusion or treatment. Other possibilities include production of nonhematopoietic stem cells such as osteogenic stromal cells, osteoblasts and rare pluripotent stem cells. Bone marrow analogs also have great potential as ex vivo human test systems and could play a critical role in drug discovery, drug development and toxicity testing in the future.

PMID: 20210588 [PubMed - in process]

 

Autobionics: a new paradigm in regenerative medicine and surgery.
March 10, 2010 at 6:32 AM

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Autobionics: a new paradigm in regenerative medicine and surgery.

Regen Med. 2010 Mar;5(2):279-88

Authors: Ashrafian H, Darzi A, Athanasiou T

The concept of bionics was developed 50 years ago and represented the development of engineering and technology based on natural biological systems. Traditional applications of bionics in healthcare include artificial bionic organs that apply engineering principles to replace or augment physiological functions by integrating electronic, mechanical or electromechanical components to inherent body tissues/organs (we term this as 'exobionics'). Recently, there has been a new wave of bio-inspired treatments that act through the reorganization of the existing biological organs in an individual to enhance physiology. Here, the technology does not replace biological tissue, but rather applies engineering principles to replace or augment physiological functions by the rearrangement and manipulation of inherent tissue/organs; we term this autobionics. Examples include: dynamic cardiomyoplasty (artificial heart pump using skeletal muscle), the Ross procedure (pulmonary auto! graft), dynamic graciloplasty (artificial sphincter) and metabolic gastric bypass (rearranging the gastrointestinal tract to modify gut- and pancreatic-hormone release). Autobionic therapies can be classified into dynamic, static and metabolic procedures. This results in tissue redesignation (one tissue used in place of another), tissue replacement and systems reorganization (rearranging inherent organ/tissue anatomy). In some cases autobionic procedures can enhance physiological function beyond normality and represents a new era in bio-inspired versatility.

PMID: 20210587 [PubMed - in process]

 

Stem cell-derived dopamine neurons for brain repair in Parkinson's disease.
March 10, 2010 at 6:32 AM

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Stem cell-derived dopamine neurons for brain repair in Parkinson's disease.

Regen Med. 2010 Mar;5(2):267-78

Authors: Fricker-Gates RA, Gates MA

One of the prospects for a curative treatment for Parkinson's disease is to replace the lost dopaminergic neurons. Preclinical and clinical trials have demonstrated that dissected fetal dopaminergic neurons have the potential to markedly improve motor function in animal models and Parkinson's disease patients. However, this source of cells will never be sufficient to use as a widespread therapy. Over the last 20 years, scientists have been searching for other reliable sources of midbrain dopamine neurons, and stem cells appear to be strong candidates. This article reviews the potential of different types of stem cells, from embryonic to adult to induced pluripotent stem cells, to see how well the cells can be differentiated into fully functional dopamine neurons, which cells might be the best candidates and how much more research is required before stem cell technology might be translated to a clinical therapy for Parkinson's disease.

PMID: 20210586 [PubMed - in process]

 

Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges.
March 10, 2010 at 6:32 AM

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Efficient isolation and chondrogenic differentiation of adult mesenchymal stem cells with fibrin microbeads and micronized collagen sponges.

Regen Med. 2010 Mar;5(2):255-65

Authors: Shainer R, Gaberman E, Levdansky L, Gorodetsky R

Background: Mesenchymal stem cells (MSCs) have been demonstrated to potentially undergo chondrogenic differentiation. We propose a new matrix for stem cell-based chondrogenesis using dense fibrin microbeads (FMBs) combined with grounded dehydrothermally crosslinked collagen sponges (micronized collagen). Methods: In this study, MSCs were isolated from bone marrow of transgenic green fluorescent protein C57/Bl mice by FMBs in high yield. After 48 h in slowly rotating suspension culture, micronized collagen was added. Results: The cells on the FMBs migrated to the collagen pieces and formed aggregates that developed into cartilage-like structures. Following chondrogenic differentiation, alcian blue staining and collagen type II immunohistochemistry demonstrated the presence of chondrocytes in the 3D structures. PCR for the expression of aggrecan and collagen type II genes supported these findings. The in vitro structures that formed were used for ectopic subdermal i! mplantation in wild-type C57/Bl mice. However, the chondrogenic markers faded relative to the pre-implant in vitro structures. Conclusion: We propose that FMBs with micronized collagen could serve as a simple technology for MSC isolation and chondrogenesis as a basis for implantation.

PMID: 20210585 [PubMed - in process]

 

Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels.
March 10, 2010 at 6:32 AM

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Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels.

Regen Med. 2010 Mar;5(2):245-53

Authors: Gu H, Yue Z, Leong WS, Nugraha B, Tan LP

Background: Mesenchymal stem cells (MSCs) are multipotent cells that can be induced to differentiate into multiple cell lineages, including neural cells. They are a good cell source for neural tissue-engineering applications. Cultivation of human (h)MSCs in 3D scaffolds is an effective means for the development of novel neural tissue-engineered constructs, and may serve as a promising strategy in the treatment of nerve injury. Aim: This study presents the in vitro growth and neural differentiation of hMSCs in 3D macroporous, cellulosic hydrogels. Results: The number of hMSCs cultivated in the 3D scaffolds increased by more than 14-fold after 7 days. After 2 days induction, most of the hMSCs in the 3D scaffolds were positive for nestin, a marker of neural stem cells. After 7 days induction, most of the hMSCs in the 3D scaffolds showed glial fibrillary acidic protein, tubulin or neurofilament M-positive reaction and a few hMSCs were positive for nestin. After 14 day! s induction, hMSCs in the 3D scaffolds could completely differentiate into neurons and glial cells. The neural differentiation of hMSCs in the 3D scaffolds was further demonstrated by real-time PCR. Conclusion: These results show that the 3D macroporous cellulosic hydrogel could be an appropriate substrate for neural differentiation of hMSCs and its possible applications in neural tissue engineering are discussed.

PMID: 20210584 [PubMed - in process]

 

Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133(+) endothelial progenitor cells for cardiac repair.
March 10, 2010 at 6:32 AM

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Therapeutic angiogenesis by transplantation of human embryonic stem cell-derived CD133(+) endothelial progenitor cells for cardiac repair.

Regen Med. 2010 Mar;5(2):231-44

Authors: Rufaihah AJ, Haider HK, Heng BC, Ye L, Tan RS, Toh WS, Tian XF, Sim EK, Cao T

Objective: This study aim to enhance endothelial differentiation of human embryonic stem cells (hESCs) by transduction of an adenovirus (Ad) vector expressing hVEGF(165) gene (Ad-hVEGF(165) ). Purified hESC-derived CD133(+) endothelial progenitors were transplanted into a rat myocardial infarct model to assess their ability to contribute to heart regeneration. Methods: Optimal transduction efficiency with high cell viability was achieved by exposing differentiating hESCs to viral particles at a ratio of 1:500 for 4 h on three consecutive days. Results: Reverse transcription-PCR analysis showed positive upregulation of VEGF, Ang-1, Flt-1, Tie-2, CD34, CD31, CD133 and Flk-1 gene expression in Ad-hVEGF(165) -transduced cells. Additionally, flow cytometric analysis of CD133, a cell surface marker, revealed an approximately fivefold increase of CD133 marker expression in Ad-hVEGF(165) -transduced cells compared with the nontransduced control. Within a rat myocardial in! farct model, transplanted CD133(+) endothelial progenitor cells survived and participated, both actively and passively, in the regeneration of the infarcted myocardium, as seen by an approximately threefold increase in mature blood vessel density (13.62 +/- 1.56 vs 5.11 +/- 1.23; p < 0.01), as well as significantly reduced infarct size (28% +/- 8.2% vs 76% +/- 5.6%; p < 0.01) in the transplanted group compared with the culture medium-injected control. There was significant improvement in heart function 6 weeks post-transplantation, as confirmed by regional blood-flow analysis (1.72 +/- 0.612 ml/min/g vs 0.8 +/- 0.256 ml/min/g; p < 0.05), as well as echocardiography assessment of left ventricular ejection fraction (60.855% +/- 7.7% vs 38.22 +/- 8.6%; p < 0.05) and fractional shortening (38.63% +/- 9.3% vs 25.2% +/- 7.11%; p < 0.05). Conclusion: hESC-derived CD133(+) endothelial progenitor cells can be utilized to regenerate the infarcted heart.

PMID: 20210583 [PubMed - in process]

 

In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.
March 10, 2010 at 6:32 AM

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In vitro study of stem cell communication via gap junctions for fibrocartilage regeneration at entheses.

Regen Med. 2010 Mar;5(2):221-9

Authors: Prasad Nayak B, Hong Goh JC, Toh SL, Satpathy GR

Background: Entheses are fibrocartilaginous organs that bridge ligament with bone at their interface and add significant insertional strength. To replace a severely damaged ligament, a tissue-engineered graft preinstalled with interfacial fibrocartilage, which is being regenerated from stem cells, appears to be more promising than ligament-alone graft. Such a concept can be realized by a biomimetic approach of establishing a dynamic communication of stem cells with bone cells and/or ligament fibroblasts in vitro. Aim: The current study has two objectives. The first objective is to demonstrate functional coculture of bone marrow-derived stem cells (BMSCs) with mature bone cells/ligament fibroblasts as evidenced by gap-junctional communication in vitro. The second objective is to investigate the role of BMSCs in the regeneration of fibrocartilage within the coculture. Materials & methods: Rabbit bone/ligament fibroblasts were dual-stained with DiI-Red and calcei! n (gap-junction permeable dye), and cocultured with unlabeled BMSCs at fixed ratio (1:10). The functional gap junction was demonstrated by the transfer of calcein from donor to recipient cells that was confirmed and quantified by flow cytometry. Type 2 collagen (cartilage extracellular matrix-specific protein) expressed by the mixed cell lines in the cocultures were estimated by real-time reverse transcription PCR and compared with that of the ligament-bone coculture (control). Results: Significant transfer of calcein into BMSCs was observed and flow cytometry analyses showed a gradual increase in the percentage of BMSCs acquiring calcein with time. Cocultures that included BMSCs expressed significantly more type 2 collagen compared with the control. Conclusion: The current study, for the first time, reported the expression of gap-junctional communication of BMSCs with two adherent cell lines of musculoskeletal system in vitro and also confirmed that incorporation of stem c! ells augments fibrocartilage regeneration. The results open up! a path to envisage a composite graft preinstalled with enthesial fibrocartilage using a stem cell-based coculture system.

PMID: 20210582 [PubMed - in process]

 

The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.
March 10, 2010 at 6:32 AM

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The effects of DNA methyltransferase inhibitors and histone deacetylase inhibitors on digit regeneration in mice.

Regen Med. 2010 Mar;5(2):201-20

Authors: Wang G, Badylak SF, Heber-Katz E, Braunhut SJ, Gudas LJ

Method: We injected two drugs that modify the epigenome, the DNA methyltransferase inhibitor 5-aza-2 -deoxycytidine (5-aza-dC) and the histone deacetylase inhibitor trichostatin A (TSA), alone or in combination, into C57Bl/6 mice subjected to amputation through the mid-second phalanx of the third digit. Wound-site tissue was collected. Results: We observed increased staining of the stem cell markers Rex1 (Zfp42) and stem cell antigen-1 at digit amputation sites from drug-treated mice. Samples from 5-aza-dC plus TSA and TSA treated mice also showed increased proliferating cell nuclear antigen staining, a measure of cell proliferation. Drug treatments increased Msx1, but not Cyp26a1 or ALDH1a2 (RALDH2) mRNA. Conclusion: 5-aza-dC and TSA treatments stimulated cell proliferation at the amputation site, possibly via increased expression of genes involved in digit development and regeneration.

PMID: 20210581 [PubMed - in process]

 

Conference Scene: Emerging themes in the stem cells space.
March 10, 2010 at 6:32 AM

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Conference Scene: Emerging themes in the stem cells space.

Regen Med. 2010 Mar;5(2):197-200

Authors: Razvi ES

The focus of this article is to present and highlight some selected topics and emerging trends from this excellent annual conference hosted by Select Biosciences Ltd. at the Embassy Suites San Francisco Airport Hotel, CA, USA. This conference attracted a worldwide audience of more than 100 delegates representing a number of different areas - basic researchers involved with stem cells, representatives from pharmaceutical, biotechnology and vendor companies, a diverse array of industry participants from the stem cell therapeutics space, as well as stem cell clinics from around the world. The scope of industry coverage presented at this conference included stem cells in cellular therapy and regenerative medicine, pluripotency/induced pluripotent stem cells, and stem cells for drug discovery and development. These categories represented the major themes into which the bulk of the presentations at this conference were organized. The major thrust of this conference was ! on the application of stem cells for cellular therapy - in this regard, it is important to note that mesenchymal stem cells are the most promising types of adult stem cells for regenerative medicine and cellular therapy. Many presentations at this conference were focused around mesenchymal stem cells for cellular therapy in a number of different disease areas.

PMID: 20210580 [PubMed - in process]

 

Company Profile: Biocompatibles International plc: local drug delivery for targeted therapies.
March 10, 2010 at 6:32 AM

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Company Profile: Biocompatibles International plc: local drug delivery for targeted therapies.

Regen Med. 2010 Mar;5(2):189-95

Authors: Coppen D

Biocompatibles International plc is focused on the development of targeted therapies for a range of indications, including oncology, neurology and cardiology. By delivering the therapy directly to the site of a localized disease numerous benefits can be achieved, including the targeting of a very high therapeutic dose to the required location and reduced systemic toxicity. As part of this strategy the company is now a leader in the field of using locally placed stem cells to make and deliver therapeutically active peptide drugs. The encapsulated cells (CellBeads((R))), modified to produce a potent anti-apoptotic peptide, CM1, are currently being evaluated in a Phase I/IIa study for the treatment of stroke and in preclinical models of acute myocardial infarction.

PMID: 20210579 [PubMed - in process]

 

Company Profile: Tissue regeneration for diabetes and neurological diseases at Living Cell Technologies.
March 10, 2010 at 6:32 AM

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Company Profile: Tissue regeneration for diabetes and neurological diseases at Living Cell Technologies.

Regen Med. 2010 Mar;5(2):181-7

Authors: Tan PLj

Living Cell Technologies' (LCT's) cell-based therapeutic for Type 1 diabetes, DIABECELL((R)), comprises encapsulated porcine insulin-producing cells. DIABECELL is presently in a Phase II clinical trial in New Zealand following positive early results. The cells are implanted into the abdomen to replace the patient's pancreatic beta-islet cells that have been lost as a result of autoimmune disease. LCT is also developing brain choroid plexus cells for the treatment of neurologic diseases. The aim is to enhance the brain's natural repair mechanism by implanting cells releasing neurotrophins. Choroid plexus cell implants alleviate disease in animal models of Parkinson's disease, Huntington's disease and stroke. LCT encapsulates all cells in alginate, permitting implantation without using immunosuppressive drugs.

PMID: 20210578 [PubMed - in process]

 

Research highlights.
March 10, 2010 at 6:32 AM

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Research highlights.

Regen Med. 2010 Mar;5(2):175-9

Authors: Kerstetter AE, Miller RH

PMID: 20210577 [PubMed - in process]

 

Industry Update: Latest developments in stem cell research and regenerative medicine.
March 10, 2010 at 6:32 AM

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Industry Update: Latest developments in stem cell research and regenerative medicine.

Regen Med. 2010 Mar;5(2):165-73

Authors: Ilic D

PMID: 20210576 [PubMed - in process]

 

News & views in ... Regenerative medicine.
March 10, 2010 at 6:32 AM

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News & views in ... Regenerative medicine.

Regen Med. 2010 Mar;5(2):161-4

Authors:

PMID: 20210575 [PubMed - in process]

 

Epidermis grafting: from adult to embryonic stem cells.
March 10, 2010 at 6:32 AM

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Epidermis grafting: from adult to embryonic stem cells.

Regen Med. 2010 Mar;5(2):157-9

Authors: Peschanski M, Lemaitre G, Nissan X, Baldeschi C

PMID: 20210574 [PubMed - in process]

 

The Translation Cycle: round and round in cycles is the only way forward for regenerative medicine.
March 10, 2010 at 6:32 AM

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The Translation Cycle: round and round in cycles is the only way forward for regenerative medicine.

Regen Med. 2010 Mar;5(2):153-5

Authors: Mason C, Manzotti E

PMID: 20210573 [PubMed - in process]

 

Nanotechnology and bone healing.
March 10, 2010 at 6:32 AM

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Nanotechnology and bone healing.

J Orthop Trauma. 2010 Mar;24 Suppl 1:S25-30

Authors: Harvey EJ, Henderson JE, Vengallatore ST

Nanotechnology and its attendant techniques have yet to make a significant impact on the science of bone healing. However, the potential benefits are immediately obvious with the result that hundreds of researchers and firms are performing the basic research needed to mature this nascent, yet soon to be fruitful niche. Together with genomics and proteomics, and combined with tissue engineering, this is the new face of orthopaedic technology. The concepts that orthopaedic surgeons recognize are fabrication processes that have resulted in porous implant substrates as bone defect augmentation and medication-carrier devices. However, there are dozens of applications in orthopaedic traumatology and bone healing for nanometer-sized entities, structures, surfaces, and devices with characteristic lengths ranging from 10s of nanometers to a few micrometers. Examples include scaffolds, delivery mechanisms, controlled modification of surface topography and composition, and b! iomicroelectromechanical systems. We review the basic science, clinical implications, and early applications of the nanotechnology revolution and emphasize the rich possibilities that exist at the crossover region between micro- and nanotechnology for developing new treatments for bone healing.

PMID: 20182231 [PubMed - in process]

 

Application of drag-reducing polymer solutions as test fluids for in vitro evaluation of potential blood damage in blood pumps.
March 10, 2010 at 6:32 AM

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Application of drag-reducing polymer solutions as test fluids for in vitro evaluation of potential blood damage in blood pumps.

ASAIO J. 2010 Jan-Feb;56(1):6-11

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 pres! sure 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 - indexed for MEDLINE]

 

Immunofluorescence microscopy for imaging of nuclear p63 in human primary keratinocytes: a comparison of antibodies and fixation methods.
March 10, 2010 at 6:32 AM

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Immunofluorescence microscopy for imaging of nuclear p63 in human primary keratinocytes: a comparison of antibodies and fixation methods.

J Immunol Methods. 2010 Jan 31;352(1-2):174-7

Authors: Markert CD, Bharadwaj S, Zhang Y, Childers MK, Furth ME

The ability of an experimental treatment to induce primitive, undifferentiated stem cells towards an epidermal fate may be tested by comparing the treated stem cells with a positive control, such as primary keratinocytes. In an effort to perfect methods used for this comparison, we tested two commercially available antibodies and three fixation methods to determine which antibody/fixation interaction produced the best immunofluorescent images of the nuclear localization of p63, a canonical marker of epidermal fate, in keratinocytes. Here, we report the methods used, and the experimental outcome.

PMID: 19925805 [PubMed - indexed for MEDLINE]

 

The cardiovascular unit as a dynamic player in disease and regeneration.
March 10, 2010 at 6:32 AM

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The cardiovascular unit as a dynamic player in disease and regeneration.

Trends Mol Med. 2009 Dec;15(12):543-52

Authors: Ausoni S, Sartore S

Cell-mediated cardiac regeneration remains a challenge as a therapeutic option in heart failure, but modest success using experimental models suggests that a better understanding of normal histogenesis will be needed to make progress towards cardiac regeneration. Recent studies of the heart show that the interstitium informs organogenesis and responsiveness to pathological stimuli through continuous bidirectional cross-talk between cardiomyocytes and non-cardiac cells. Here, we introduce the concept of the "cardiovascular unit" (CVU) as a building block of the heart, which includes cardiomyocytes and adjacent capillaries and fibroblasts. We discuss how the CVU might be used as a tool for re-interpreting degenerative changes of the myocardium during aging and hypertrophy, and might represent the hallmark for successful cell therapy strategies in cardiac regeneration.

PMID: 19913457 [PubMed - indexed for MEDLINE]

 

Optimized aerosol delivery to a mechanically ventilated rodent.
March 10, 2010 at 6:32 AM

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Optimized aerosol delivery to a mechanically ventilated rodent.

J Aerosol Med Pulm Drug Deliv. 2009 Dec;22(4):323-32

Authors: MacLoughlin RJ, Higgins BD, Laffey JG, O'Brien T

BACKGROUND: Aerosol delivery through an endotracheal tube during mechanical ventilation of small animals, simulating neonates and small infants, has shown to be influenced by a variety of factors including aerosol generator type, droplet/particle size, ventilator circuitry and ventilation regime. A review of the literature indicates that reported aerosol deposition rates in rodents are quite low, with lung deposition in anesthetized, mechanically ventilated rats reported to be approximately 3.9 and approximately 8% in anesthetized, spontaneously breathing rats. The optimization of aerosol delivery to both in vitro and in vivo models of anesthetized mechanically ventilated rodents is described in this study. METHODS: Characterization and optimization of the in vitro system performance relied on gravimetric analysis, laser diffraction droplet sizing, and spectrophotometric analysis of drug mass on inspiratory filters. The optimized setup was subsequently employed in! vivo to determine deposition of a tracer aerosol in the rat lung. RESULTS: In vitro testing confirmed that droplet size, ventilation regimen, breath actuation setting, and the inclusion of a drug recycling step had the greatest effect on inhaled mass. During testing, improvements of up to 41% were seen in inhaled mass values between runs with the addition of a recycling step. The negative effects of the aerosolization process on albuterol sulphate were minimal. In vitro deposition rates of 29.95 +/- 1.54% of the original dose were recorded (n = 3). In vivo deposition rates of Evans blue were highly comparable (30.88 +/- 5.73%) (n = 6). Intratracheal instillation of the tracer dye resulted in deposition of 87.34 +/- 6.23% of the original dose. CONCLUSIONS: This optimized experimental setup allows for greater inhaled mass than previously reported. The addition of a recycling step may prove to be a significant improvement in achieving higher deposition in mechanically ventila! ted lungs; however, the suitability of the test agent for repe! ated neb ulization needs assessment.

PMID: 19415985 [PubMed - indexed for MEDLINE]

 

Extraction and separation of proteoglycans.
March 10, 2010 at 6:32 AM

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Extraction and separation of proteoglycans.

Glycoconj J. 2009 Nov;26(8):953-9

Authors: Yanagishita M, Podyma-Inoue KA, Yokoyama M

Proteoglycans contain a unique carbohydrate component, glycosaminoglycan, which consists of repeating, typically sulfated disaccharides, and is capable of interacting with diverse molecules. Specific, clustered arrangements of sulfate on the glycosaminoglycan backbone form binding sites for many biologically important ligands such as extracellular matrix molecules and growth factors. Core proteins of proteoglycans also show molecular interactions necessary for organizing scaffolds in the extracellular matrix or for anchoring proteoglycans to the plasma membrane. Experimental protocols aiming at extracting maximal amounts of proteoglycans from tissues or cells require disruption of molecular interactions involving proteoglycans by denaturing solvents. Among many of the proteoglycan separation procedures, anion exchange chromatography, which takes advantage of the presence of highly negatively charged glycosaminoglycans in all proteoglycans, serves one of the most c! onvenient general separation techniques.

PMID: 18493850 [PubMed - indexed for MEDLINE]

 

[PDGF-BB initiates vascular smooth muscle-like phenotype differentiation of human bone marrow mesenchymal stem cells in vitro]
March 10, 2010 at 6:32 AM

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[PDGF-BB initiates vascular smooth muscle-like phenotype differentiation of human bone marrow mesenchymal stem cells in vitro]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 Jul;23(4):335-9

Authors: Wu YC, Cui L, Li G, Yin S, Gao YJ, Cao YL

OBJECTIVE: To investigate the feasibility of human bone marrow mesenchymal stem cells (hBMSCs) in vitro differentiation into vascular smooth muscle cells with induction of platelet-derived growth Factor BB (PDGF-BB). METHODS: Bone marrow mesenchymal stem cells of adult healthy donors were separated from iliac crest aspiration and expanded in DMEM-LG medium. Cells at passage 1 were transferred to EGM-2 medium containing PDGF-BB (20 ng/ml) and cultured for 14 days. The expression of SM alpha-actin, SM calponin, SMMHC and SM 22alpha were detected by immunofluorescence and observed with fluorescence microscope. mRNA expression of SMalpha-actin, SM calponin, SMMHC as well as SM 22alpha was analyzed by RT-PCR. The method of Western-Blot was applied to determine protein expression of SM 22alpha. Cells with induction were observed for the expression of SM alpha-actin,SM calponin,SMMHC by FACs analysis. RESULTS: With the induction of PDGF-BB, the morphology of cells change! d to a spindle fibroblastic appearance. By fluorescence microscope observation, expression of SM alpha-actin, SM calponin and SMMHC was found intracellularly in PDGF-BB treated hBMSCs at 14 days. Western-Blot detection confirmed SM 22alpha expression by 14 days induction. RT-PCR of characteristic vascular smooth muscle cells related genes, such as SM alpha-actin, SM calponin, SMMHC and SM 22alpha revealed differentiation of vascular smooth muscle cells phenotype in monolayer culture upon stimulation with PDGF-BB for 14 days. The positive expression of SM alpha-actin, SM calponin and SMMHC in induced cells was significantly higher than that in non-induced cells (P < 0.05, n=3). CONCLUSION: These results suggested hBMSCs could be differentiated into vascular smooth muscle cell phenotype with PDGF-BB induction in vitro.

PMID: 17926862 [PubMed - indexed for MEDLINE]

 

[Microarray analysis of dedifferentiation related gene expression of human chondrocytes cultured in vitro]
March 10, 2010 at 6:32 AM

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[Microarray analysis of dedifferentiation related gene expression of human chondrocytes cultured in vitro]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 Jul;23(4):331-4

Authors: Zhang Y, Chai G, Liu W, Zhou GD, Cui L, Cao YL

OBJECTIVE: Dedifferentiation of chondrocytes during in vitro expansion is the major cause that limits the potential of chondrocytes for cartilage engineering. This study dissected dedifferentiation mechanism of in vitro cultured human chondrocytes by microarray analysis of gene expression changes. METHODS: Spare human costal cartilage from ear reconstruction patients (n=3, aged 10-20) were digested with collagenase II to isolate human chondrocytes(HCC) and were expanded from P1 to P4. For microarray, RNA was isolated from the P1 and P4 cells and labeled with cy3 and cy5 fluorescence respectively as probes to hybridize a cDNA microarray( about 8300 genes). Those genes with 2-fold difference of expression were selected. RESULTS: Microarray results showed that 56 genes were up-regulated at P4, including proteases, inflammatory factors, growth suppressor and apoptosis genes. Down-regulated 84 genes at P4 include extracellular matrices, protein anabolism, growth factor! s, cell cycle and cytoskeleton related genes. CONCLUSIONS: These results provide insight into the mechanism of chondrocytes dedifferentiation. The characteristic appearance of dedifferentiation related genes expression includes increased level of stress response and inflammation. The down-regulation of anabolic metabolism related genes and up-regulation of proteases genes leaded to extra cellular matrix decrease. Decreased production of growth factors and increased apoptosis cause decreased cell proliferation of dedifferentiation chondrocytes.

PMID: 17926861 [PubMed - indexed for MEDLINE]

 

[Biocompatibility of decellularized canine carotid artery allograft cross-linked by carbodiimide]
March 10, 2010 at 6:32 AM

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[Biocompatibility of decellularized canine carotid artery allograft cross-linked by carbodiimide]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 May;23(3):244-7

Authors: Hao CG, Yang DP, Ma H, Han XF, Guo TF

OBJECTIVE Crosslink decellularized canine carotid artery allograft by EDC [1-3-(dimethylamino)propyl-3-ethylcarbodiimide methiodide] and evaluate the biocompatibility of it. METHODS: Use the multi-step detergent-enzyme method to construct decellularized canine carotid artery allograft and cross-link it by EDC with the weight ratio of decellularized artery to EDC 1:1 and 1:2. Evaluate the biocompatibility of it by the cytotoxical MTT test and the rat subdermal bury test. RESULTS: Decellularized canine carotid artery cross-linked by EDC has a lower degradation rate treated by collagenase type II, the result of MTT test show that the EDC cross-linked decellularized artery has no cytotoxity and the rat subdermal bury test show that crosslinking greatly enhance the ability of decellularize artery to resist the enzyme degradation and lower the immune reaction. The more the artery was cross-linked , the more effects it has. CONCLUSIONS: Decellularized canine carotid arte! ry cross-linked by EDC has fairly good biocompatibility and ability to resist the collagenase degradation.

PMID: 17649951 [PubMed - indexed for MEDLINE]

 

[Pilot study of using autologous bone marrow stromal cells and coral to repair canine segmental mandibular defects]
March 10, 2010 at 6:32 AM

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[Pilot study of using autologous bone marrow stromal cells and coral to repair canine segmental mandibular defects]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 Jan;23(1):51-5

Authors: Yuan J, Liu GP, Chai G, Liu B, Xu F, Cui L, Liu W, Cao YL

OBJECTIVE: To repair segmental mandibular defects with autologous bone marrow stromal cells (BMSCs) engineered bone. METHODS: Isolated BMSCs were expanded in vitro and osteogenic induced. In 12 canines, a 3 cm segmental mandibular defect at right mandible was created. 6 canine's defects were repaired with cell-scaffold constructs made from induced BMSCs and coral; others were repaired with coral as control. The engineered bone was evaluated by X-ray, CT, Dual Energy X-ray Absorptiometry (DXA), gross and histological examination, and biomechanical test post-operatively. RESULTS: Induced BMSCs grew well on coral scaffold. At 12 weeks, X-ray showed more callus formed in experimental group, while evident scaffold duration in control group. At 32 weeks, gross observation, X-ray and CT demonstrated well bony-union in experimental group, while bony-nonunion in control group. Also DXA revealed significantly higher bone mineral density of experimental group than control gr! oup. Histologically, mature bone were commonly observed and there were bony healing in experimental group, while fibrous healing occurred in control group. Biomechanical test revealed no significant difference between experimental group and normal group. CONCLUSIONS: Canine segmental mandibular defects can be repaired with the tissue-engineered bone generated by coral scaffold with autologous osteogenic BMSCs.

PMID: 17393696 [PubMed - indexed for MEDLINE]

 

[An investigation of restoration of alveolar cleft with engineered bone]
March 10, 2010 at 6:32 AM

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[An investigation of restoration of alveolar cleft with engineered bone]

Zhonghua Zheng Xing Wai Ke Za Zhi. 2007 Jan;23(1):29-31

Authors: Ou XR, Jian XC, Lin G

OBJECTIVE: To investigate restoration of alveolar cleft with engineered bone constructed by sponge collagen protein combined bone mesenchymal stem cells (BMSC). METHODS: Twelve dogs were divided into 4 groups, the third incisor and alveolar bone with periosteum in bilateral maxilla were removed to form alveolar cleft model. The BMSCs were isolated from dog bone marrow. After being cultured and induced, the BMSCs were seeded in sponge collagen protein and cultured for 48 hours. The composites of BMSCs and collagen were implanted into the defect of alveolar cleft. After 12 weeks' feeding, those dogs were sacrificed. Three-dimensional CT and histological examination were used to observe the progress of bone formation. RESULTS: The defects healed at 12 weeks after being implant BMSCs-collagen composites, the width of engineered bone is resembled with positive control, but the height is less than positive control. CONCLUSIONS: The engineered bone can restore the defect! of alveolar bone effectively, it can be used clinically to treat alveolar cleft.

PMID: 17393689 [PubMed - indexed for MEDLINE]

 

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