| Multiple myeloma patients experience high response rate with new 3-drug combination
December 5, 2009 at 7:39 pm
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| Chemical synthesis and characterization of silver-protected vasoactive intestinal peptide nanoparticles.
December 5, 2009 at 6:37 am
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| | Chemical synthesis and characterization of silver-protected vasoactive intestinal peptide nanoparticles. Nanomed. 2009 Dec;4(8):919-30 Authors: Fernandez-Montesinos R, Castillo PM, Klippstein R, Gonzalez-Rey E, Mejias JA, Zaderenko AP, Pozo D We characterized a method to conjugate functional silver nanoparticles with vasoactive intestinal peptide (VIP), which could be used as a working model for further tailor-made applications based on VIP surface functionality. Despite sustained interest in the therapeutic applications of VIP, and the fact that its drugability could be largely improved by the attachament to functionalized metal nanoparticles, no methods have been described so far to obtain them. Materials & methods: VIP was conjugated to tiopronin-capped silver nanoparticles of a narrow size distribution, by means of proper linkers, to obtain VIP functionalized silver nanoparticles with two different VIP orientations (Ag-tiopronin-PEG-succinic-[His]VIP and Ag-tiopronin-PEG-VIP[His]). VIP intermediate nanoparticles were characterized by transmission-electron microscopy and Fourier transform infrared spectroscopy. VIP functionalized silver nanoparticles cytotoxicity was determined by lactate dehydrogenase release from mixed glial cultures prepared from cerebral cortices of 1-3 days-old C57/Bl mice. Cells were used for lipopolysaccharide stimulation at day 18-22 of culture. Results: Two different types of VIP-functionalized silver nanoparticles were obtained; both expose the C-terminal part of the neuropeptide, but in the first type VIP is attached to silver nanoparticle through its free amine terminus (Ag-tiopronin-PEG-succinic-[His]VIP), while in the second type, VIP N-terminus remains free (Ag-tiopronin-PEG-VIP[His]). VIP-functionalized silver nanoparticles did not compromise cellular viability and inhibited microglia-induced stimulation under inflammatory conditions. Conclusion: The chemical synthesis procedure developed to obtain VIP-functionalized silver nanoparticles rendered functional products, in terms of biological activity. The two alternative orientations designed, reduced the constraints for chemical synthesis that depends on the nanosurface to be functionalized. Our study provides, for the first time, a proof of principle to enhance the therapeutic potential of VIP with the valuable properties of metal nanoparticles for imaging, targeting and drug delivery. PMID: 19958228 [PubMed - in process] |
| New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity.
December 5, 2009 at 6:37 am
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| | New emerging potentials for human Wharton's jelly mesenchymal stem cells: immunological features and hepatocyte-like differentiative capacity. Stem Cells Dev. 2009 Dec 3; Authors: Anzalone R, Lo Iacono M, Corrao S, Magno F, Loria T, Cappello F, Zummo G, Farina F, La Rocca G In recent years, human mesenchymal stem cells (MSC) have been extensively studied. Their key characteristics of long-term self-renewal and a capacity to differentiate into diverse mature tissues favour their use in regenerative medicine applications. Stem cells can be found in embryonic and extra-embryonic tissues as well as in adult organs. Several reports indicate that cells of Wharton's jelly (WJ), the main component of umbilical cord extracellular matrix, are multipotent stem cells, expressing markers of bone marrow mesenchymal stem cells (BM-MSC), and giving rise to different cellular types of both connective and nervous tissues. Wharton's jelly mesenchymal stem cells (WJ-MSC) express markers previously characterized in embryonic stem cells (ESC), such as Nanog and Oct3/4A. WJ-MSC further emerge as promising hypoimmunogenic cells, due to the expression of molecules able to modulate NK cells and expand regulatory T cells populations. Moreover, it is now accepted that the differentiative capacities of such cells span all the mesoderm-derived tissues, extending to neuroectodermal as well as endodermal lineages. In this review we compare very recent data on the potential of WJ-MSC to undergo hepatocyte-like differentiation with the results obtained from other adult MSC populations. Data in the literature strongly suggest that WJ-MSC can differentiate into diverse cell types, showing a unique ability to cross lineage borders. This, together with their in vitro proliferative potential and their immunoregulatory features, renders these cells extremely promising for regenerative medicine applications in different pathological settings. PMID: 19958166 [PubMed - as supplied by publisher] |
| Regulation of the chondrogenic phenotype in culture.
December 5, 2009 at 6:16 am
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| | Regulation of the chondrogenic phenotype in culture. Birth Defects Res C Embryo Today. 2009 Dec 3;87(4):351-371 Authors: Bobick BE, Chen FH, Le AM, Tuan RS In recent years, there has been a great deal of interest in the development of regenerative approaches to produce hyaline cartilage ex vivo that can be utilized for the repair or replacement of damaged or diseased tissue. It is clinically imperative that cartilage engineered in vitro mimics the molecular composition and organization of and exhibits biomechanical properties similar to persistent hyaline cartilage in vivo. Experimentally, much of our current knowledge pertaining to the regulation of cartilage formation, or chondrogenesis, has been acquired in vitro utilizing high-density cultures of undifferentiated chondroprogenitor cells stimulated to differentiate into chondrocytes. In this review, we describe the extracellular matrix molecules, nuclear transcription factors, cytoplasmic protein kinases, cytoskeletal components, and plasma membrane receptors that characterize cells undergoing chondrogenesis in vitro and regulate the progression of these cells through the chondrogenic differentiation program. We also provide an extensive list of growth factors and other extracellular signaling molecules, as well as chromatin remodeling proteins such as histone deacetylases, known to regulate chondrogenic differentiation in culture. In addition, we selectively highlight experiments that demonstrate how an understanding of normal hyaline cartilage formation can lead to the development of novel cartilage tissue engineering strategies. Finally, we present directions for future studies that may yield information applicable to the in vitro generation of hyaline cartilage that more closely resembles native tissue. Birth Defects Research (Part C) 87:351-371, 2009. Published 2009 by Wiley-Liss, Inc. PMID: 19960542 [PubMed - as supplied by publisher] |
| Potency of double-layered Poly L-lactic Acid scaffold in tissue engineering of tendon tissue.
December 5, 2009 at 6:16 am
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| | Potency of double-layered Poly L-lactic Acid scaffold in tissue engineering of tendon tissue. Int Orthop. 2009 Dec 5; Authors: Inui A, Kokubu T, Makino T, Nagura I, Toyokawa N, Sakata R, Kotera M, Nishino T, Fujioka H, Kurosaka M A successful scaffold for use in tendon tissue engineering requires a high affinity for living organisms and the ability to maintain its mechanical strength until maturation of the regenerated tissue. We compared two types of poly(L-lactic acid) (PLLA) scaffolds for use in tendon regeneration, a plain-woven PLLA fabric (fabric P) with a smooth surface only and a double layered PLLA fabric (fabric D) with a smooth surface on one side and a rough (pile-finished) surface on the other side. These two types of fabric were implanted into the back muscles of rabbits and evaluated at three and six weeks after implantation. Histological examination showed collagen tissues were highly regenerated on the rough surface of fabric D. On the other hand, liner cell attachment was seen in the smooth surface of fabric P and fabric D. The total DNA amount was significantly higher in fabric D. Additionally, mechanical examination showed fabric P had lost its mechanical strength by six weeks after implantation, while the strength of fabric D was maintained. Fabric D had more cell migration on one side and less cell adhesion on the other side and maintained its initial strength. Thus, a novel form of double-layered PLLA fabric has the potential to be used as a scaffold in tendon regeneration. PMID: 19960193 [PubMed - as supplied by publisher] |
| Differentiation of Adult Stem Cells into Smooth Muscle for Vascular Tissue Engineering.
December 5, 2009 at 6:16 am
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| | Differentiation of Adult Stem Cells into Smooth Muscle for Vascular Tissue Engineering. J Surg Res. 2009 Sep 4; Authors: Harris LJ, Abdollahi H, Zhang P, McIlhenny S, Tulenko TN, Dimuzio PJ BACKGROUND: Herein we evaluate the potential of adipose-derived stem cells (ASC) to differentiate into smooth muscle cells (SMC) and their potential for use in a tissue-engineered vascular graft. MATERIALS AND METHODS: We isolated ASC (CD13+29+90+) from the peri-umbilical adipose tissue of patients undergoing vascular surgery, and cultured them in media containing angiotensin II (AngII), sphingosylphosphorylcholine (SPC), or transforming growth factor-beta 1 (TGFbeta1) for up to 3 weeks. SMC differentiation was assessed by (1) expression of early (calponin, caldesmon) and late (myosin heavy chain, MHC) SMC markers by RT-PCR, qPCR and Western blot, and (2) contraction upon plating on collagen gel. Differentiated ASCs were seeded onto a vascular graft (decellularized saphenous vein) within a bioreactor, and cell attachment was determined using confocal microscopy. RESULTS: Prior to differentiation, ASC expressed low levels of all three molecular markers. After culture in each differentiating medium, the extent of up-regulation of calponin, caldesmon, and MHC was variable across all cell lines. After seeding onto collagen gel, ASCs differentiated in SPC and TGFbeta1 exhibit contractile properties, similar to smooth muscle cell controls. Differentiated stem cells adhered and proliferated on the vascular graft. CONCLUSION: These data suggest that human adipose-derived stem cells (1) exhibit variable expression of SMC molecular markers after differentiation, (2) exhibit a contractile phenotype after differentiation with SPC and TGFbeta1, and (3) proliferate on a vascular graft scaffold. Thus, ASCs are potentially useful in the construction of autologous arteries. PMID: 19959190 [PubMed - as supplied by publisher] |
| Tissue engineering for conjunctival reconstruction: established methods and future outlooks.
December 5, 2009 at 6:16 am
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| | Tissue engineering for conjunctival reconstruction: established methods and future outlooks. Curr Eye Res. 2009 Nov;34(11):913-24 Authors: Schrader S, Notara M, Beaconsfield M, Tuft SJ, Daniels JT, Geerling G Reconstruction of the conjunctiva is an essential part of ocular surface regeneration, especially if an extensive area or the whole ocular surface is affected, such as in patients with ocular cicatricial pemphigoid, Stevens-Johnson syndrome, toxic epidermal necrolysis, or chemical/thermal burns. In these situations, corneal reconstruction almost inevitably fails unless the conjunctival surface is first repaired and a deep fornix is restored. The growing field of tissue engineering and advances in stem cell research offer promising new alternatives for these challenges. This article reviews the present approaches for reconstruction of the conjunctival surface, considering the established strategies and new potential methodologies. PMID: 19958107 [PubMed - in process] |
| Silk fibroin microparticles as carriers for delivery of human recombinant BMP-2.
December 5, 2009 at 6:16 am
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| | Silk fibroin microparticles as carriers for delivery of human recombinant BMP-2. Tissue Eng Part C Methods. 2009 Dec 3; Authors: Bessa PC, Balmayor ER, Hartinger J, Zanoni G, Dopler D, Meinl A, Banerjee A, Casal M, Redl H, Reis RL, van Griensven M The in vitro and in vivo efficiency of fibroin microparticles as a delivery carrier for bone morphogenetic protein-2 (BMP-2) was evaluated. BMP-2 was encapsulated in silk fibroin particles, produced by a simple and very mild processing method. The dose-response of BMP-2 loaded fibroin particles was examined in C2C12 cells, after 5 days of culture. The BMP-2 retained most of its activity as observed by the increase in ALP activity, which was much higher when BMP-2 was encapsulated into the particles rather than just surface-adsorbed. After 2 weeks of culture, increased mineralization was observed with BMP-2 loaded particles in comparison to soluble added growth factor. No significant cytotoxicity was detected. When implanted in a rat ectopic model, bone formation was observed by in vivo muCT after 2 and 4 weeks post-implantation, with particles loaded with 5 or 12.5 mug BMP-2. An increase in bone density was observed over time. Histology revealed further evidence of ectopic bone formation, observed by strong Alizarin Red staining and osteocalcin immunostaining. Our findings show that fibroin microparticles may present an interesting option for future clinical applications in the bone tissue engineering field. Further studies are planned. PMID: 19958078 [PubMed - as supplied by publisher] |
| [Enhancing effect of tissue engineered bone on bone defect repair in rats]
December 5, 2009 at 6:16 am
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| | [Enhancing effect of tissue engineered bone on bone defect repair in rats] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Oct;23(10):1250-3 Authors: Song H, Li Q, Li B, Wang Z OBJECTIVE: To evaluate the effects of composite bone in strategy of tissue engineering on bone defect repair in rats. METHODS: Sixteen matured Wistar rats (male or female, weighing 250-300 g) were used to prepare platelet lysate (PL). PL/allogeneic decalcified bone granules (ADBG)/Col I (PAC) and ADBG/Col I (AC) were prepared by mixing Col I gel ADBG with or without PL. BMSCs of 8 Wistar rats (male or female, weighing 250-300 g) were isolated and cultured. The 5th passage of BMSCs were co-cultured with PAC at the density of 1 x 10(6) cells/mL to fabricate the tissue engineered composite PACB in vitro. Forty healthy Wistar rats were made bilateral bone defects in femoral condyles and divided into 4 groups (A, B, C and D, n=10). The defects were filled with equivalent PACB, PAC, AC and Col I in groups A, B, C and D respectively. At 4 weeks, the defect repair was evaluated with radiology, histology, ALP biochemical tests. RESULTS: At 4 weeks, the bone density measurement was (7.31 +/- 0.54), (4.36 +/- 0.67), (2.12 +/- 0.47), and (1.09 +/- 0.55) pixels in groups A, B, C, and D, respectively. The area of new bone formation in defect area under single view was (412.82 +/- 22.31), (266.57 +/- 17.22), (94.34 +/- 20.22), and (26.12 +/- 12.51) pixels in groups A, B, C and D respectively. The ALP contents in femoral condyles were (94.31 +/- 7.54), (69.88 +/- 4.12), (41.33 +/- 3.46), and (21.03 +/- 3.11) U/L, respectively. The above indexes of group A were significantly higher than those of groups B, C or D (P < 0.05). Three-color flow cytometry assay showed that the T lymphocyte subsets of CD3(+)CD4(+)CD8(-), CD3(+)CD8(+)CD4(-), and the ratio of CD4/CD8 displayed no significant difference among four groups (P > 0.05). CONCLUSION: Tissue engineered bone PACB is capable to promote the bone defect repair. PMID: 19957850 [PubMed - in process] |
| [Effect of vitreous-cryopreservation on in vivo implantation of tissue engineered tendons]
December 5, 2009 at 6:16 am
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| | [Effect of vitreous-cryopreservation on in vivo implantation of tissue engineered tendons] Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2009 Oct;23(10):1229-34 Authors: Liao M, Liu C, Zhu M, Qin T OBJECTIVE: To study the immunological rejection occurred in different period after the in vivo implantation of vitreous-cryopreservation tissue engineered tendons for the repair of tendon defect and investigate its influences on the hepatic, renal, and cardiovascular function of rats. METHODS: Tenocytes obtained from tail tendon of one-week-old SD rats were cultured in vitro. The tenocytes at passage 2-4 (5 x 10(6) cells/mL) were co-cultured with 1.5 cm bio-derived tendon material to reconstruct tissue engineered tendon. The 21% DMSO was used as cryopreservation protection solution and the Eurocollins solution served as basic solution for pre-frozen solution (4 degrees C) and eluent. The cell-scaffold composites were vitreous-cryopreserved by self-designed method. Seventy-two healthy SD rats (male and/or female) weighing 210-230 g were randomly divided into three groups: group A (n = 32), group B (n = 32), and group C (n = 8). The 0.5 cm tendon defect model was established in the middle part of Achilles tendon in groups A and B. The defect in group A and B was repaired by the transplantation of tissue engineered tendon with and without vitreous-cryopreservation, respectively. At 2, 4, 6, and 8 weeks after transplantation, the general observation and the detection of hepatic function, renal function, and cardiovascular function were conducted. At 2, 4, and 6 weeks after transplantation, serum immunology test was conducted. RESULTS: There were no tissue necrosis, hydrops, and suppurative infection in groups A and B. The adhesion was evident in groups A and B 2 weeks after transplantation, improved gradually during 4-6 weeks, and disappeared at 8 weeks. The neonatal tissue had full integration and continuity, and the bridging region of the tendon healed and was similar to the normal tendon. For serum IgG and IgM content, there was no significant difference when group A or B was compared with group C, and between group A and group B 2, 4, and 6 weeks after transplantation (P > 0.05). Hepatic function: aspartate aminotransferase (AST) content of group A was less than that of group C 4 weeks after transplantation (P < 0.05); AST content of group B was less than that of group C 4 and 6 weeks after transplantation (P < 0.05); but there was no significant difference when group A or B was compared with group C in terms of other indexes 8 weeks after transplantation (P > 0.05). Renal function: serum albumin and creatinine in groups A and B were decreased obviously, and significant difference was evident when compared with group C (P < 0.05). Cardiovascular function: there was no significant difference between group A and group C in terms of blood glucose, triglyceride, and cholesterol (P > 0.05); there was a significant difference between group B and group C in terms of triglyceride 8 weeks after transplantation (P < 0.05). CONCLUSION: Repairing tendon defect with the implantation of vitreous-cryopreservation tissue engineered tendons results in no obvious immunological rejection and exerts no obvious influences on hepatic, renal, and cardiovascular function. PMID: 19957846 [PubMed - in process] |
| Art, Bill, Nadia and Stem Cell Billions
December 5, 2009 at 3:01 am
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| | The vice chairman of the $3 billion California stem cell agency, Art Torres, today will return to his old roots as a campaigner when he hits the hustings on behalf of the wife of the state treasurer, Bill Lockyer. Torres(at left), who is up for a pay increase at the CIRM board meeting next week, will be "pounding the pavement" in Hayward for Nadia Lockyer, who is running for a seat on the Alameda | | | 
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