Thursday, April 7, 2011

4/7 TE-RegenMed-StemCell feed

     
    TE-RegenMed-StemCell feed    
   
Sailing with the Tide
April 7, 2011 at 3:16 PM
 
are once again hoisting sail to move farther south (actually east and south) towards Panama. That means a hiatus in fresh items on the California Stem Cell Report at least until we find another Internet connection. How long will the break be? That is unknown but probably not more than three weeks. Less if we find an Internet cafe in one of the villages along the coast of Costa Rica or Panama.
   
   
Inhibition of p53-p21 pathway promotes the differentiation of rat bone marrow mesenchymal stem cells into cardiomyocytes.
April 7, 2011 at 11:09 AM
 

Inhibition of p53-p21 pathway promotes the differentiation of rat bone marrow mesenchymal stem cells into cardiomyocytes.

Mol Cell Biochem. 2011 Apr 6;

Authors: Yan X, Lv A, Xing Y, Liu B, Hou J, Huang W, Li Y

P53 is shown recently to play an important role in the proliferation and differentiation of bone marrow mesenchymal stem cells (BMMSCs). In this study, by inhibiting p53-p21 pathway with p53 inhibitor (p-fifty three inhibitor-alpha, PFT-α), we investigated the resulting effects on the differentiation of rat BMMSCs into cardiomyocyte-like cells. BMMSCs were isolated from bone marrow of SD rats by density gradient centrifugation. The fourth passage cells were divided into four groups: control group, PFT-α group, 5-AZA group, and PFT-α + 5-AZA group. The purified BMMSCs were identified by surface antigens and the proliferation and apoptosis of BMMSCs were examined by MTT and flow cytometry analysis. The expression of cTnI and CX-43 in BMMSCs after induction was detected by immunofluorescence and that of cTnI, p53, and p21 was detected by western blot. Our results demonstrated that PFT-α at 20 μmol/l significantly reduced the apoptosis and promoted the proliferation of BMMSCs, and induced BMMSCs to differentiate into cardiomyocyte-like cells. In conclusion, these data open up new possibility of modulating p53-p21 pathway for directed differentiation of BMMSCs into cardiomyocytes, which will be valuable for cardiovascular regenerative medicine.

PMID: 21468649 [PubMed - as supplied by publisher]

   
   
Killing of myeloid APC via HLA Class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells.
April 7, 2011 at 11:09 AM
 

Killing of myeloid APC via HLA Class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells.

Eur J Immunol. 2011 Apr 6;

Authors: Magnani CF, Alberigo G, Bacchetta R, Serafini G, Andreani M, Roncarolo MG, Gregori S

IL-10-producing CD4(+) type 1 regulatory T (Tr1) cells, defined based on their ability to produce high levels of IL-10 in the absence of IL-4, are major players in the induction and maintenance of peripheral tolerance. Tr1 cells inhibit T cell responses mainly via cytokine-dependent mechanisms. The cellular and molecular mechanisms underlying the suppression of APC by Tr1 cells are still not completely elucidated. Here, we defined that Tr1 cells specifically lyse myeloid APC through a granzyme B (GZB)- and perforin (PRF)- dependent mechanism that requires HLA class I recognition, CD54/Lymphocyte Function-associated Antigen (LFA)-1 adhesion, and activation via KIR and CD2. Notably, interaction between CD226 on Tr1 cells and their ligands on myeloid cells, leading to Tr1 cell activation, is necessary for defining Tr1 cell target specificity. We also showed that high frequency of GZB expressing CD4(+) T cells is detected in tolerant patients and correlates with elevated occurrence of IL-10-producing CD4(+) T cells. In conclusion, the modulatory activities of Tr1 cells are not only due to suppressive cytokines but also to specific cell-to-cell interactions which lead to selective killing of myeloid cells and possibly bystander suppression.

PMID: 21469116 [PubMed - as supplied by publisher]

   
   
Wound microenvironment sequesters adipose-derived stem cells in a murine model of reconstructive surgery in the setting of concurrent distant malignancy.
April 7, 2011 at 8:44 AM
 

Wound microenvironment sequesters adipose-derived stem cells in a murine model of reconstructive surgery in the setting of concurrent distant malignancy.

Plast Reconstr Surg. 2011 Apr;127(4):1467-77

Authors: Altman AM, Prantl L, Muehlberg FL, Song YH, Seidensticker M, Butler CE, Alt EU

: It is unclear whether mesenchymal stem cells that are applied to regenerate wound tissues can migrate to existing tumors and enhance their growth. The authors investigated whether adipose-derived stem cells had any effect on the growth and progression of distant tumors when applied to a skin wound.

PMID: 21460655 [PubMed - in process]

   
   
ANGIOGRAPHIC DEMONSTRATION OF NEOANGIOGENESIS AFTER INTRA-ARTERIAL INFUSION OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS IN DIABETIC PATIENTS WITH CRITICAL LIMB ISCHAEMIA.
April 7, 2011 at 8:44 AM
 

ANGIOGRAPHIC DEMONSTRATION OF NEOANGIOGENESIS AFTER INTRA-ARTERIAL INFUSION OF AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS IN DIABETIC PATIENTS WITH CRITICAL LIMB ISCHAEMIA.

Cell Transplant. 2011 Apr 1;

Authors: Ruiz-Salmeron R, de la Cuesta-Diaz A, Constantino-Bermejo M, Pérez-Camacho I, Marcos-Sánchez F, Hmadcha A, Soria B

Critical limb ischaemia in diabetic patients is associated with high rates of morbidity and mortality. Sub-optimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10⁶ cells) in 20 diabetic patients with severe below-the-knee arterial ischaemia. Although the time-course of clinical effects differed among patients, after 12 months of follow-up, all patients presented a notable improvement in the Rutherford-Becker classification; the University of Texas diabetic wound scales and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischaemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischaemic areas and promotes remarkable clinical improvement.

PMID: 21457613 [PubMed - as supplied by publisher]

   
   
A more efficient method to generate integration-free human iPS cells.
April 7, 2011 at 8:44 AM
 

A more efficient method to generate integration-free human iPS cells.

Nat Methods. 2011 Apr 3;

Authors: Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka KI, Shibata T, Kunisada T, Takahashi M, Takahashi J, Saji H, Yamanaka S

We report a simple method, using p53 suppression and nontransforming L-Myc, to generate human induced pluripotent stem cells (iPSCs) with episomal plasmid vectors. We generated human iPSCs from multiple donors, including two putative human leukocyte antigen (HLA)-homozygous donors who match ∼20% of the Japanese population at major HLA loci; most iPSCs are integrated transgene-free. This method may provide iPSCs suitable for autologous and allologous stem-cell therapy in the future.

PMID: 21460823 [PubMed - as supplied by publisher]

   
   
Effects of BMP-2 and vitamin D(3) on the osteogenic differentiation of adipose stem cells.
April 7, 2011 at 2:25 AM
 

Effects of BMP-2 and vitamin D(3) on the osteogenic differentiation of adipose stem cells.

Biochem Biophys Res Commun. 2011 Apr 1;

Authors: Song I, Kim BS, Kim CS, Im GI

We studied the effect of bone morphogenetic protein-2 (BMP-2) and vitamin D(3) on the osteogenic differentiation of adipose stem cells (ASCs). ASCs were treated with 10, 50, 100ng/ml of BMP-2, and 10(-8), 10(-7), 10(-6)M vitamin D(3.) Then, to investigate the effects of combined treatment, ASCs were treated with BMP-2 and vitamin D(3) dose-dependently and time-dependently. The osteogenic differentiation was assessed by alkaline phosphatase (ALP) activities/staining and the mineralization was evaluated by Alizarin red staining. ALP activity and mineralization dose-dependently increased in early stages (ALP on 7(th) day and mineralization on the 14(th) day) while all three doses of BMP-2 or vitamin D(3) showed comparable effects in late stages (ALP on the 14(th) day and mineralization on the 21(st) day) in ASCs. BMP-2 and vitamin D3 had synergistic effect on the osteogenic differentiation of ASCs. While all three doses of BMP-2 acted similarly in reinforcing the effect of vitamin D(3), vitamin D(3) dose-dependently augmented the osteogenic effect of BMP-2. When BMP-2 was constantly treated, vitamin D(3) effect did not differ depending on the period of vitamin D(3) treatment. However, when vitamin D3 was constantly treated, the BMP was more effective when treated for the last 7 days than when treated for the first 7 days. In conclusion, BMP-2 and vitamin D3 promote osteogenic differentiation of ASCs, and can work synergistically. These results can be used to induce effective and economical osteogenic induction of ASCs for bone tissue engineering.

PMID: 21463608 [PubMed - as supplied by publisher]

   
   
Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable polyurethane scaffold.
April 7, 2011 at 2:25 AM
 

Functional characterization of human coronary artery smooth muscle cells under cyclic mechanical strain in a degradable polyurethane scaffold.

Biomaterials. 2011 Apr 2;

Authors: Sharifpoor S, Simmons CA, Labow RS, Paul Santerre J

There are few synthetic elastomeric biomaterials that simultaneously provide the required biological conditioning and the ability to translate biomechanical stimuli to vascular smooth muscle cells (VSMCs). Biomechanical stresses are important physiological elements that regulate VSMC function, and polyurethane elastomers are a class of materials capable of facilitating the translation of stress induced biomechanics. In this study, human coronary artery smooth muscle cells (hCASMCs), which were seeded into a porous degradable polar/hydrophobic/ionic (D-PHI) polyurethane scaffold, were subjected to uniaxial cyclic mechanical strain (CMS) over a span of four weeks using a customized bioreactor. The distribution, proliferation and contractile protein expression of hCASMCs in the scaffold were then analyzed and compared to those grown under static conditions. Four weeks of CMS, applied to the elastomeric scaffold, resulted in statistically greater DNA mass, more cell area coverage and a better distribution of cells deeper within the scaffold construct. Furthermore, CMS samples demonstrated improved tensile mechanical properties following four weeks of culture, suggesting the generation of more extracellular matrix within the polyurethane constructs. The expression of smooth muscle α-actin, calponin and smooth muscle myosin heavy chain and the absence of Ki-67+ cells in both static and CMS cultures, throughout the 4 weeks, suggest that hCASMCs retained their contractile character on these biomaterials. The study highlights the importance of implementing physiologically-relevant biomechanical stimuli in the development of synthetic elastomeric tissue engineering scaffolds.

PMID: 21463894 [PubMed - as supplied by publisher]

   
   
Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs.
April 7, 2011 at 2:25 AM
 

Comparably accelerated vascularization by preincorporation of aortic fragments and mesenchymal stem cells in implanted tissue engineering constructs.

J Biomed Mater Res A. 2011 Apr 4;

Authors: Schumann P, von See C, Kampmann A, Lindhorst D, Tavassol F, Kokemüller H, Bormann KH, Gellrich NC, Rücker M

The demanding need for tissue replacement resulted in manifold approaches for the construction of different tissues. One common problem which hampers the clinical usage of tissue engineering constructs is a limited vascularization. In an attempt to accelerate the vascularization of tissue engineering constructs we compared the usage of bone marrow mesenchymal stem cells (bmMSCs) and fragments derived from the aorta in vivo. Tissue engineering constructs composed of PLGA scaffolds containing Matrigel (n = 8), aortic fragments embedded in Matrigel (n = 8), bmMSCs embedded in Matrigel (n = 8), and aortic fragments embedded in Matrigel combined with bmMSCs (n = 8) were implanted into dorsal skinfold chambers of balb/c mice and analyzed repetitively over 14 days. In all groups a weak inflammatory response was transiently apparent. Vascularization was significantly (p = 0.05) accelerated in bmMSC and aortic fragments containing constructs compared with Matrigel alone, demonstrated by a distinctly increased microvascular density throughout the whole experiment. The combination of bmMSCs and aortic fragments showed no additional effect compared with bmMSCs and aortic fragments alone. The accelerated vascularization and microvascular density of tissue engineering constructs triggered by bmMSCs and aortic fragments is comparable. Thus aortic fragments provide a new promising source for clinical relevant tissue engineering constructs. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.

PMID: 21465643 [PubMed - as supplied by publisher]

   
   
Three-dimensional glass-derived scaffolds for bone tissue engineering: Current trends and forecasts for the future.
April 7, 2011 at 2:25 AM
 

Three-dimensional glass-derived scaffolds for bone tissue engineering: Current trends and forecasts for the future.

J Biomed Mater Res A. 2011 Apr 4;

Authors: Baino F, Vitale-Brovarone C

Biomaterials used in regenerative medicine are often designed to act as 3D porous templates (scaffolds) able to support and promote the growth and repair of natural tissues. Some types of glasses have a great potential for making bone tissue engineering scaffolds, as they can bond to host bone, stimulate bone cells toward osteogenesis, and resorb at the same time as the bone is repaired. This review article highlights the evolution of glass-based scaffolds for bone tissue engineering; specifically, the features, limitations, and advantages of the different types of glass-derived scaffolds proposed in the literature (macroporous glass-ceramic, sol-gel glass, composite, graded, hybrid, and hierarchical implants) are critically examined, discussed, and compared. Future directions for the research are also suggested, highlighting the promise of multifunctional systems able to combine bone regeneration and drug release abilities, the increasing role of nondestructive advanced imaging techniques, such as X-ray microtomography, for scaffolds investigation and the potential of stem cells incorporation into scaffolds. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.

PMID: 21465645 [PubMed - as supplied by publisher]

   
   
Fabrication of fibrinogen/P(LLA-CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications.
April 7, 2011 at 2:25 AM
 

Fabrication of fibrinogen/P(LLA-CL) hybrid nanofibrous scaffold for potential soft tissue engineering applications.

J Biomed Mater Res A. 2011 Apr 4;

Authors: He C, Xu X, Zhang F, Cao L, Feng W, Wang H, Mo X

Coelectrospinning of native proteins and elastic synthetic polymers is an attractive technique to fabricate hybrid fibrous scaffolds that combine the bioactivity and mechanical features of each material component. In this study, hybrid fibrous scaffolds composed of synthetic P(LLA-CL) elastomeric and naturally derived fibrinogen protein were fabricated and characterized for their bioactive and physiochemical properties. Fiber diameters of hybrid scaffolds increased with increasing P(LLA-CL) content, and the shape of fibers changed from cylindrical shape on pure polymer scaffolds to flat structure on hybrid scaffolds. Characterizations of ATR-FTIR, XRD, and thermal properties indicated that the hybrid scaffolds contain two different phases, one composed of pure fibrinogen and the other corresponding to a mixture of fibrinogen and P(LLA-CL), and no obvious chemical reaction takes place between two components. The hybrid fibrous scaffolds showed tailorable degradation rates than pure P(LLA-CL) and higher mechanical properties than pure fibrinogen, and both tensile strength and breaking strain increased with increasing P(LLA-CL) content. In Vitro studies revealed that L929 cells on hybrid scaffolds achieved relatively higher level of cell attachment after 12 h of culture and significant increased cell proliferation rate after 7 days of culture, when compared with pure fibrinogen and P(LLA-CL) scaffolds, and the cells exhibited a spreading polygonal shape on the hybrid fibrous surfaces compared to a round shape on surfaces of pure polymer scaffolds. Therefore, the fibrinogen/P(LLA-CL) hybrid fibrous scaffolds possess the combined benefits of each individual component, which make it capable as scaffolds for soft tissue reconstruction. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011.

PMID: 21465642 [PubMed - as supplied by publisher]

   
   
Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery.
April 7, 2011 at 2:25 AM
 

Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery.

Int Urogynecol J Pelvic Floor Dysfunct. 2010 Sep;21(9):1085-93

Authors: Hung MJ, Wen MC, Hung CN, Ho ES, Chen GD, Yang VC

Mesh-augmented reconstructive surgery for pelvic organ prolapse (POP) does not meet clinical expectations. A tissue-engineered fascia equivalent needs to be developed.

PMID: 20480140 [PubMed - indexed for MEDLINE]

   
   
Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2.
April 7, 2011 at 2:25 AM
 

Reconstruction of the alveolar cleft: can growth factor-aided tissue engineering replace autologous bone grafting? A literature review and systematic review of results obtained with bone morphogenetic protein-2.

Clin Oral Investig. 2011 Apr 5;

Authors: van Hout WM, Mink van der Molen AB, Breugem CC, Koole R, Van Cann EM

The alveolar cleft in patients with clefts of lip, alveolus and palate (CLAP) is usually reconstructed with an autologous bone graft. Harvesting of autologous bone grafts is associated with more or less donor site morbidity. Donor site morbidity could be eliminated if bone is fabricated by growth factor-aided tissue engineering. The objective of this review was to provide an oversight on the current state of the art in growth factor-aided tissue engineering with regard to reconstruction of the alveolar cleft in CLAP. Medline, Embase and Central databases were searched for articles on bone morphogenetic protein 2 (BMP-2), bone morphogenetic protein 7, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factor, fibroblast growth factor, vascular endothelial growth factor and platelet-rich plasma for the reconstruction of the alveolar cleft in CLAP. Two-hundred ninety-one unique search results were found. Three articles met our selection criteria. These three selected articles compared BMP-2-aided bone tissue engineering with iliac crest bone grafting by clinical and radiographic examinations. Bone quantity appeared comparable between the two methods in patients treated during the stage of mixed dentition, whereas bone quantity appeared superior in the BMP-2 group in skeletally mature patients. Favourable results with BMP-2-aided bone tissue engineering have been reported for the reconstruction of the alveolar cleft in CLAP. More studies are necessary to assess the quality of bone. Advantages are shortening of the operation time, absence of donor site morbidity, shorter hospital stay and reduction of overall cost.

PMID: 21465220 [PubMed - as supplied by publisher]

   
     
 
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