Thursday, September 3, 2009

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StemCells, Inc. Demonstrates Protection of Neurological Function in Batten Mouse
September 3, 2009 at 1:06 pm


NOXXON Is Awarded Research and Development Grant for First-in-Human Clinical Trial with Spiegelmer® NOX-A12
September 3, 2009 at 9:05 am


Development of robotic dispensed bioactive scaffolds and human adipose-derived stem cell culturing for bone tissue engineering.
September 3, 2009 at 7:48 am

Related Articles

Development of robotic dispensed bioactive scaffolds and human adipose-derived stem cell culturing for bone tissue engineering.

Tissue Eng Part C Methods. 2009 Sep 1;

Authors: Oh CH, Hong SJ, Jeong I, Yu HS, Jegal SH, Kim HW

Bioactive and degradable scaffolds made from bioactive glass - polycaprolactone with a mineralized surface and a well-defined 3-dimensional (3D) pore-configuration were produced using a robotic dispensing technique. Human adipose-derived stem cells (hASCs) were cultured on the 3D scaffolds and the osteogenic development of cells within the scaffolds was addressed under a dynamic flow perfusion system for bone tissue engineering. The bioactive glass component introduced within the composite assisted in the surface mineralization of the 3D scaffolds. The hASCs initially adhered well and grew actively over the mineralized surface, and migrated deep into the channels of the 3D scaffold. In particular, dynamic perfusion culturing helped the cells to proliferate better on the 3D structure compared to that under static culturing condition. After 4 weeks culturing by dynamic perfusion, the cells not only covered the scaffold surface completely but also filled the pore channels bridging the stems. The osteogenic differentiation of the hASCs with the input of osteogenic factors was stimulated significantly by the dynamic perfusion flow, as determined by alkaline phosphate expression. Overall, the culturing of hASCs upon the currently-developed 3D scaffold in conjunction with dynamic perfusion method may be useful for the tissue engineering of bone.

PMID: 19722827 [PubMed - as supplied by publisher]


Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering.
September 3, 2009 at 7:30 am

Related Articles

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering.

J Cell Physiol. 2009 Sep 1;

Authors: Richardson SM, Hoyland JA, Mobasheri R, Csaki C, Shakibaei M, Mobasheri A

Defects of load-bearing connective tissues such as articular cartilage and intervertebral disc (IVD) can result from trauma, degenerative, endocrine, or age-related disease. Current surgical and pharmacological options for the treatment of arthritic rheumatic conditions in the joints and spine are ineffective. Cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. This review focuses on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. Here we discuss the prospects of using MSCs in regenerative medicine and summarize the advantages and disadvantages of these cells in articular cartilage and IVD tissue engineering. We discuss the conceptual and practical difficulties associated with differentiating and pre-conditioning MSCs for subsequent survival in a physiologically harsh extracellular matrix, an environment that will be highly hypoxic, acidic, and nutrient deprived. Implanted MSCs will be exposed to traumatic physical loads and high levels of locally produced inflammatory mediators and catabolic cytokines. We also explore the potential of culture models of MSCs, fully differentiated cells and co-cultures as "proof of principle" ethically acceptable "3Rs" models for engineering articular cartilage and IVD in vitro for the purpose of replacing the use of animals in arthritis research. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 19725073 [PubMed - as supplied by publisher]


Lubricin distribution in the human intervertebral disc.
September 3, 2009 at 7:30 am

Related Articles

Lubricin distribution in the human intervertebral disc.

J Bone Joint Surg Am. 2009 Sep;91(9):2205-12

Authors: Shine KM, Simson JA, Spector M

BACKGROUND: Previous studies have identified lubricin (also known as superficial zone protein) as a lubricating glycoprotein present in several musculoskeletal tissues including articular cartilage, meniscus, and tendon. In this immunohistochemical study, we determined the presence and distribution of lubricin in the cells, extracellular matrix, and tissue surfaces of human nucleus pulposus and anulus fibrosus tissues. METHODS: Twenty-eight human intervertebral discs were resected at autopsy from fourteen cadavers. Disc specimens were fixed in formalin, processed, and paraffin-embedded prior to sectioning. Tissue sections were immunohistochemically stained for lubricin, the extent of extracellular matrix staining was evaluated semiquantitatively, and cellular staining was assessed quantitatively with use of a survey method. RESULTS: Lubricin staining was evident in the extracellular matrix and at select surfaces of the nucleus pulposus and anulus fibrosus tissues. The extent of lubricin staining of the extracellular matrix was contingent on the disc region (nucleus pulposus, inner anulus fibrosus, or outer anulus fibrosus), with the greatest extent of matrix staining found in the nucleus pulposus, but it was not contingent on the Thompson grade. A subset of disc cells within the nucleus, inner anulus, and outer anulus also stained positively for lubricin, suggesting intrinsic cell synthesis of the glycoprotein. The disc region significantly affected the percentage of lubricin-staining cells, with the greatest percentage of cells staining for lubricin (nearly 10%) found in the nucleus pulposus. The percentage of cells staining for lubricin correlated with the extent of extracellular matrix staining for lubricin. CONCLUSIONS: The results of this study confirm the presence of lubricin in the human intervertebral disc and demonstrate a unique distribution compared with that in the goat. The presence of lubricin in asymptomatic discs provides a foundation for future research regarding the role of lubricin in pathological disc conditions.

PMID: 19723998 [PubMed - in process]


Optimization of polyurethane structure for bone tissue engineering applications.
September 3, 2009 at 7:30 am

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Optimization of polyurethane structure for bone tissue engineering applications.

Acta Biomater. 2009 Aug 29;

Authors: Bil M, Ryszkowska J, Woźniak P, Kurzydłowski KJ, Lewandowska-Szumieł M

Polyurethanes containing 22 to 70 wt.% hard segments were developed and evaluated for bone tissue engineering applications. Aliphatic poly(ester-urethanes) were synthesised from poly(epsilon-caprolactone) diol (PCL) with different molecular masses (Mn = approximately 530, 1250, 2000 Da), cycloaliphatic diisocyanate 4, 4'-methylenebis(cyclohexyl isocyanate) (HMDI) and ethylene glycol (EG) as a chain extender. Changes in macromolecule order with increasing hard segment content were observed via modulated differential scanning calorimetry (MDSC). Depending on the hard segment content, a gradual variation in polyurethane surface properties was revealed by Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and static contact angle measurements. As the hard segments content was increased, the polyurethane surface exhibited more phase separation, higher content of urethane moieties and higher hydrophilicity. The biocompatibility results indicated that proliferation of Human Bone Derived Cells (HBDCs) cultured in vitro improved with increasing hard segment content while osteogenic potential of HBDCs decreased with increasing hard segment content.

PMID: 19723595 [PubMed - as supplied by publisher]


Biomimetic macroporous hydrogels: protein ligand distribution and cell response to the ligand architecture in the scaffold.
September 3, 2009 at 7:30 am

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Biomimetic macroporous hydrogels: protein ligand distribution and cell response to the ligand architecture in the scaffold.

J Biomater Sci Polym Ed. 2009;20(12):1781-95

Authors: Savina IN, Dainiak M, Jungvid H, Mikhalovsky SV, Galaev IY

Macroporous hydrogels (MHs), cryogels, are a new type of biomaterials for tissue engineering that can be produced from any natural or synthetic polymer that forms a gel. Synthetic MHs are rendered bioactive by surface or bulk modifications with extracellular matrix components. In this study, cell response to the architecture of protein ligands, bovine type-I collagen (CG) and human fibrinogen (Fg), immobilised using different methods on poly(2-hydroxyethyl methacrylate) (pHEMA) macroporous hydrogels (MHs) was analysed. Bulk modification was performed by cross-linking cryo-co-polymerisation of HEMA and poly(ethylene glycol)diacrylate (PEGA) in the presence of proteins (CG/pHEMA and Fg/pHEMA MHs). The polymer surface was modified by covalent immobilisation of the proteins to the active epoxy (ep) groups present on pHEMA after hydrogel fabrication (CG-epHEMA and Fg-epHEMA MHs). The concentration of proteins in protein/pHEMA and protein-epHEMA MHs was 80-85 and 130-140 mug/ml hydrogel, respectively. It was demonstrated by immunostaining and confocal laser scanning microscopy that bulk modification resulted in spreading of CG in the polymer matrix and spot-like distribution of Fg. On the contrary, surface modification resulted in spot-like distribution of CG and uniform spreading of Fg, which evenly coated the surface. Proliferation rate of fibroblasts was higher on MHs with even distribution of the ligands, i.e., on Fg-epHEMA and CG/pHEMA. After 30 days of growth, fibroblasts formed several monolayers and deposited extracellular matrix filling the pores of these MHs. The best result in terms of cell proliferation was obtained on Fg-epHEMA. The ligands displayed on surface of these scaffolds were in native conformation, while in bulk-modified CG/pHEMA MHs most of the proteins were buried inside the polymer matrix and were less accessible for interactions with specific antibodies and cells. The method used for MH modification with bioligands strongly affects spatial distribution, density and conformation of the ligand on the scaffold surface, which, in turn, influence cell-surface interactions. The optimal type of modification varies depending on intrinsic properties of proteins and MHs.

PMID: 19723441 [PubMed - in process]


Effects of Oligo(3-hydroxyalkanoates) on the Viability and Insulin Secretion of Murine Beta Cells.
September 3, 2009 at 7:30 am

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Effects of Oligo(3-hydroxyalkanoates) on the Viability and Insulin Secretion of Murine Beta Cells.

J Biomater Sci Polym Ed. 2009;20(12):1729-46

Authors: Yang XD, Zou XH, Dai ZW, Luo RC, Wei CJ, Chen GQ

Biopolyesters of polyhydroxyalkanoates (PHAs), including poly-3-hydroxybutyrate (PHB), co-polyester of 3-hydroxybutyrate and 4-hydroxybutyrate (P3HB4HB), and co-polyester of 3-hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) have been well investigated for their biocompatibility. For in vivo application, it is very important that the degradation products of PHAs, especially the oligomers, are not harmful to the cells and surrounding tissues. In this study, in vitro effects of oligo(3-hydroxybutyrate) (OHB), oligo(3-hydroxybutyrate-co-4-hydroxybutyrate) (O3HB4HB) and oligo(3-hydroxybutyrate-co-3-hydroxyhexanoate) (OHBHHx) on growth and differentiation of the murine beta cell line NIT-1 were investigated. Among the three oligo-hydroxyalkanoates (Oligo-HAs), cells treated with OHBHHx displayed higher viability, as measured by CCK-8 assay. Flow cytometric analysis of NIT-1 cells indicated that Oligo-HAs had an inhibitory effect on cell apoptosis. The cytosolic Ca(2+) transient of NIT-1 cells increased when fed with 0.04 g/l Oligo-HAs. For gap junction intercellular communication of cells, the effect of OHBHHx was the best among all materials tested. More importantly, extracellular insulin secretion was up-regulated after growing in OHBHHx for 48 h. The results demonstrated that the degradation products of PHAs, especially OHBHHx from PHBHHx, were not harmful to the beta cells. Therefore, PHBHHx warrant further study for application as a pancreatic tissue engineering material.

PMID: 19723438 [PubMed - in process]


Tissue engineering of the anterior cruciate ligament: the viscoelastic behavior and cell viability of a novel braid-twist scaffold.
September 3, 2009 at 7:30 am

Related Articles

Tissue engineering of the anterior cruciate ligament: the viscoelastic behavior and cell viability of a novel braid-twist scaffold.

J Biomater Sci Polym Ed. 2009;20(12):1709-28

Authors: Freeman JW, Woods MD, Cromer DA, Wright LD, Laurencin CT

The anterior cruciate ligament (ACL) is the most commonly injured ligament of the knee; it also contributes to normal knee function and stability. Due to its poor healing potential severe ACL damage requires surgical intervention, ranging from suturing to complete replacement. Current ACL replacements have a host of limitations that prevent their extensive use. Investigators have begun to utilize tissue-engineering techniques to create new options for ACL repair, regeneration and replacement. In this study we tested novel braid-twist scaffolds, as well as braided scaffolds, twisted fiber scaffolds and aligned fiber scaffolds, for use as ACL replacements composed of poly(L-lactic acid) fibers. Scaffolds were examined using stress relaxation tests, cell viability assays and scanning electron microscopy. The behaviors of the braid-twist scaffolds were modeled with Maxwell and quasi-linear viscoelastic (QLV) models. In stress relaxation tests, the braid-twist scaffolds behaved similarly to native ACL tissue, with final normalized stresses of 87% and 83% after an 8 N load. There was agreement between the experimental data and the Maxwell model when the model included an element for each structural element in the scaffold. There was also agreement between the experimental data and QLV model, scaffolds with similar braiding angles shared constants. In cell proliferation studies no differences were found between fibroblast growth on the braided scaffolds and the braid-twist scaffolds. SEM images showed the presence of new extracellular matrix. Data from this and previous tensile studies demonstrate that the braid-twist scaffold design may be effective in scaffolds for ACL tissue regeneration.

PMID: 19723437 [PubMed - in process]


Plant polyphenols effectively protect HaCaT cells from ultraviolet C-triggered necrosis and suppress inflammatory chemokine expression.
September 3, 2009 at 7:30 am

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Plant polyphenols effectively protect HaCaT cells from ultraviolet C-triggered necrosis and suppress inflammatory chemokine expression.

Ann N Y Acad Sci. 2009 Aug;1171:305-13

Authors: Pastore S, Potapovich A, Kostyuk V, Mariani V, Lulli D, De Luca C, Korkina L

Oxidative stress is a common response of epidermal cells to a variety of noxious stimuli such as ultraviolet (UV) radiation from solar light and proinflammatory cytokines from skin-infiltrating leukocytes. Here, we report that two types of plant-derived antioxidants, the phenylpropanoid glycoside verbascoside as well as the flavonoids rutin and quercetin possess protective effects against UVC-induced cell damage and proinflammatory activation. The molecules under investigation were effective against the loss of cell integrity associated with necrosis in doses consistent with their antioxidant activity, whereas they did not significantly oppose UVC-induced proliferation arrest and apoptosis. By contrast, only verbascoside effectively inhibited cytokine-induced release of proinflammatory mediators in a dose-dependent fashion. Verbascoside and its homologue teupolioside dramatically impaired NF-kappaB and AP-1 DNA binding activity. These results suggest that plant polyphenols with antioxidant properties have distinct mechanisms in the suppression of oxidative stress induced in keratinocytes by different stimuli. Verbascoside and teupolioside are hence of potential interest in the protection of the skin from both environmental and inflammatory insults.

PMID: 19723070 [PubMed - in process]


Development of robotic dispensed bioactive scaffolds and human adipose-derived stem cell culturing for bone tissue engineering.
September 3, 2009 at 7:30 am

Related Articles

Development of robotic dispensed bioactive scaffolds and human adipose-derived stem cell culturing for bone tissue engineering.

Tissue Eng Part C Methods. 2009 Sep 1;

Authors: Oh CH, Hong SJ, Jeong I, Yu HS, Jegal SH, Kim HW

Bioactive and degradable scaffolds made from bioactive glass - polycaprolactone with a mineralized surface and a well-defined 3-dimensional (3D) pore-configuration were produced using a robotic dispensing technique. Human adipose-derived stem cells (hASCs) were cultured on the 3D scaffolds and the osteogenic development of cells within the scaffolds was addressed under a dynamic flow perfusion system for bone tissue engineering. The bioactive glass component introduced within the composite assisted in the surface mineralization of the 3D scaffolds. The hASCs initially adhered well and grew actively over the mineralized surface, and migrated deep into the channels of the 3D scaffold. In particular, dynamic perfusion culturing helped the cells to proliferate better on the 3D structure compared to that under static culturing condition. After 4 weeks culturing by dynamic perfusion, the cells not only covered the scaffold surface completely but also filled the pore channels bridging the stems. The osteogenic differentiation of the hASCs with the input of osteogenic factors was stimulated significantly by the dynamic perfusion flow, as determined by alkaline phosphate expression. Overall, the culturing of hASCs upon the currently-developed 3D scaffold in conjunction with dynamic perfusion method may be useful for the tissue engineering of bone.

PMID: 19722827 [PubMed - as supplied by publisher]


Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold.
September 3, 2009 at 7:30 am

Related Articles

Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold.

Biomacromolecules. 2009 Aug 10;10(8):2240-4

Authors: Wang S, Zhang Y, Wang H, Yin G, Dong Z

In this study, a tubular scaffold composed of polylactide fibers (outside layer) and silk fibroin-gelatin fibers (inner layer) was fabricated successfully by electrospinning. Morphological, biomechanical, and dissolvable properties of the composite scaffolds were examined, in particular, biocompatibility of the scaffolds were evaluated in vitro and in vivo by means of cell culture and subcutaneous implantation test. The PLA/SF-gelatin tubular scaffolds, with porosity of approximately 82 +/- 2%, possessed appropriate breaking strength (2.21 +/- 0.18 MPa), pliability (60.58 +/- 1.23%), and suture retention strength (4.58 +/- 0.62 N). The burst pressure strength of the composite scaffolds reached 1596 +/- 20 mmHg, which is much greater than that of the native vessels. The composite scaffolds could hardly dissolve in the water; the water-dissolved rate was only 0.3 +/- 0.1%. MTT assay and SEM observation indicated that both 3T3 mouse fibroblasts and human umbilical vein endothelial cells could adhere, spread, and proliferate well on the composite tubular scaffolds after culturing for 14 and 21 days, respectively. The subcutaneous implantation results showed that macrophages and lymphocytes were not observed, which indicated that the composite scaffolds could induce minor inflammatory reactions in vivo. The PLA/SF-gelatin tubular scaffolds are biocompatible, possess appropriate biomechanical properties, and provide a favorable environment that supports the growth of cells, which shows that the composite tube can be considered as an ideal candidate for tissue engineering blood vessel.

PMID: 19722559 [PubMed - in process]


Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration.
September 3, 2009 at 7:30 am

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Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration.

Cytotherapy. 2009;11(4):377-91

Authors: Kode JA, Mukherjee S, Joglekar MV, Hardikar AA

Mesenchymal stem cells (MSC) are multipotent cells that differentiate into osteoblasts, myocytes, chondrocytes and adipocytes as well as insulin-producing cells. The mechanism underlying their in vivo differentiation is not clear and is thought to be caused by spontaneous cell fusion or factors present in the microenvironment. However, their ease of isolation, high 'ex-vivo' expansion potential and ability to differentiate into multiple lineages make them attractive tools for potential use in cell therapy. MSC have been isolated from several tissues, including bone/bone marrow, fat, Wharton's jelly, umbilical cord blood, placenta and pancreas. The 'immunosuppressive' property of human MSC makes them an important candidate for cellular therapy in allogeneic settings. Use of allogeneic MSC for repair of large defects may be an alternative to autologous and allogeneic tissue-grafting procedures. An allogeneic approach would enable MSC to be isolated from any donor, expanded and cryopreserved, providing a readily available source of progenitors for cell replacement therapy. Their immunomodulatory properties have raised the possibility of establishing allogeneic MSC banks for tissue regeneration. These facts are strongly reflected in the current exponential growth in stem cell research in the pharmaceutical and biotechnology communities. Current knowledge regarding the immunobiology and clinical application of MSC needs to be strengthened further to establish MSC as a safe and effective therapeutic tool in regenerative medicine. This paper discusses human MSC with particular reference to the expression of their surface markers, their role as immunomodulators and their multilineage differentiation potential and possible use in tissue regeneration and repair.

PMID: 19568970 [PubMed - indexed for MEDLINE]


Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells.
September 3, 2009 at 7:30 am

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Sternal repair with bone grafts engineered from amniotic mesenchymal stem cells.

J Pediatr Surg. 2009 Jun;44(6):1120-6; discussion 1126

Authors: Steigman SA, Ahmed A, Shanti RM, Tuan RS, Valim C, Fauza DO

PURPOSE: We aimed at determining whether osseous grafts engineered from amniotic mesenchymal stem cells (aMSCs) could be used in postnatal sternal repair. METHODS: Leporine aMSCs were isolated, identified, transfected with green fluorescent protein (GFP), expanded, and seeded onto biodegradable electrospun nanofibrous scaffolds (n = 6). Constructs were dynamically maintained in an osteogenic medium and equally divided into 2 groups with respect to time in vitro as follows: 14.6 or 33.9 weeks. They were then used to repair full-thickness sternal defects spanning 2 to 3 intercostal spaces in allogeneic kits (n = 6). Grafts were submitted to multiple analyses 2 months thereafter. RESULTS: Chest roentgenograms showed defect closure in all animals, confirmed at necropsy. Graft density as assessed by microcomputed tomographic scans increased significantly in vivo, yet there were no differences in mineralization by extracellular calcium measurements preimplantation and postimplantation. There was a borderline increase in alkaline phosphatase activity in vivo, suggesting ongoing graft remodeling. Histologically, implants contained GFP-positive cells and few mononuclear infiltrates. There were no differences between the 2 construct groups in any comparison. CONCLUSIONS: Engineered osseous grafts derived from amniotic mesenchymal stem cells may become a viable alternative for sternal repair. The amniotic fluid can be a practical cell source for engineered chest wall reconstruction.

PMID: 19524727 [PubMed - indexed for MEDLINE]


Effects of 20% demineralization on surface physical properties of compact bone scaffold and bone remodeling response at interface after orthotopic implantation.
September 3, 2009 at 7:30 am

Related Articles

Effects of 20% demineralization on surface physical properties of compact bone scaffold and bone remodeling response at interface after orthotopic implantation.

Bone. 2009 Aug;45(2):301-8

Authors: Mo XT, Yang ZM, Qin TW

To enhance osteointegration with preservation of mechanical strength, a surface modification technique using 20% surface demineralization in a controlled manner was applied to custom-built cylindrical bio-derived compact bones (20% surface-demineralized cylindrical compact bio-derived bone scaffold: SDCBS); an undemineralized version was the control. The micro-surface topography of the two types of bone scaffolds was characterized by atomic force microscopy (AFM) and scanning electron microscopy (SEM). 20% demineralization led to significant increases in surface roughness (38.19%, P=0.001) and surface area (15.1%, P=0.030), compared with the control group's, while the decrease in mechanical properties was not statistically significant. Results of orthotopic implantation for 9 months demonstrated that 20% surface demineralization caused significantly rapid and homogeneous bone remodeling at the interface compared to control and led to a significantly rapid osteointegration of SDCBS with the host bone at the early and intermediate stages of osteointegration. The study indicates the potential of SDCBS in repairing clinical bone defects, and would help direct the use of various processes of biomaterials to support defect repairs within osseous sites.

PMID: 19376281 [PubMed - indexed for MEDLINE]


Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering.
September 3, 2009 at 6:58 am

Mesenchymal stem cells in regenerative medicine: Opportunities and challenges for articular cartilage and intervertebral disc tissue engineering.

J Cell Physiol. 2009 Sep 1;

Authors: Richardson SM, Hoyland JA, Mobasheri R, Csaki C, Shakibaei M, Mobasheri A

Defects of load-bearing connective tissues such as articular cartilage and intervertebral disc (IVD) can result from trauma, degenerative, endocrine, or age-related disease. Current surgical and pharmacological options for the treatment of arthritic rheumatic conditions in the joints and spine are ineffective. Cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. This review focuses on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. Here we discuss the prospects of using MSCs in regenerative medicine and summarize the advantages and disadvantages of these cells in articular cartilage and IVD tissue engineering. We discuss the conceptual and practical difficulties associated with differentiating and pre-conditioning MSCs for subsequent survival in a physiologically harsh extracellular matrix, an environment that will be highly hypoxic, acidic, and nutrient deprived. Implanted MSCs will be exposed to traumatic physical loads and high levels of locally produced inflammatory mediators and catabolic cytokines. We also explore the potential of culture models of MSCs, fully differentiated cells and co-cultures as "proof of principle" ethically acceptable "3Rs" models for engineering articular cartilage and IVD in vitro for the purpose of replacing the use of animals in arthritis research. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.

PMID: 19725073 [PubMed - as supplied by publisher]


Validation System of Tissue Engineered Epithelial Cell Sheets for Corneal Regenerative Medicine.
September 3, 2009 at 6:58 am

Validation System of Tissue Engineered Epithelial Cell Sheets for Corneal Regenerative Medicine.

Tissue Eng Part C Methods. 2009 Sep 1;

Authors: Hayashi R, Yamato M, Takayanagi H, Oie Y, Kubota A, Hori Y, Okano T, Nishida K

Recently, regenerative therapy with tissue engineered epithelial cell sheets has been performed for treating ocular surface disease. It would be required to develop the validation method for these cell sheets to standardize and spread the regenerative therapy. In the present study, we developed a validation system for cultivated epithelial cell sheets. Human limbal epithelial cells and human oral mucosal epithelial cells were cultured with 3T3 feeder layer cells on temperature-responsive culture inserts for three different culture periods, and subjected to cell sheet harvest and validation. Epithelial cells cultured for a short period weren't successfully harvested as intact contiguous cell sheets. On the other hand, total cell number and viability of epithelial cell sheets harvested after prolonged culture period decreased. Furthermore, these cells also lost epithelial barrier function. These results showed the potential effectiveness of the proposed validation system that can evaluate fabricated cell sheets before transplantation.

PMID: 19722828 [PubMed - as supplied by publisher]

 

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