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| Human Umbilical Cord Blood as an Emerging Stem Cell Therapy for Diabetes Mellitus.
June 10, 2010 at 8:04 AM
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| | Human Umbilical Cord Blood as an Emerging Stem Cell Therapy for Diabetes Mellitus. Curr Stem Cell Res Ther. 2010 Jun 9; Authors: Reddi AS, Kuppasani K, Ende N Cellular therapy for patients with diabetes is receiving great attention among scientists and clinicians. Bone marrow is considered one of the rich sources of stem cells. However, the limited availability of bone marrow donors precludes its use for all the suitable patients. Human umbilical cord blood (HUCB) is being increasingly used as an alternative source of stem cells for cell-based therapy for malignant and nonmalignant diseases. HUCB is preferred to bone marrow because of its easy availability, low potential for graft-versus-host disease and tumorigenicity as well as infectious complications. Furthermore, no immunosuppression is required. In vitro and in vivo studies have shown that HUCB-derived stem cells can differentiate into insulin-secreting beta-cells. Administration of HUCB cells has been shown to improve blood glucose levels in diabetic animals. The first use of autologous HUCB transfusion in type 1 diabetic children is showing promise in reducing the daily requirement of insulin dose and the maintenance of near normoglycemia over a short period of time. The time has come for more clinical trials using autologous and allogenic cord blood transfusion to treat diabetes mellitus. PMID: 20528762 [PubMed - as supplied by publisher] | | |
| Therapeutic Window, a Critical Developmental Stage for Stem Cell Therapies.
June 10, 2010 at 8:04 AM
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| | Therapeutic Window, a Critical Developmental Stage for Stem Cell Therapies. Curr Stem Cell Res Ther. 2010 Jun 9; Authors: Li SC, Han YP, Dethlefs BA, Loudon WG In children, cancers are the deadliest of diseases and second only to accidents as the leading cause of death. The deadliest of the brain cancers are the malignant gliomas. Approximately two-thirds of children can survive less malignant types of brain cancers, however, in approximately 67% of these survivors recurs under the current regimes of surgery followed by administration of high doses toxic drugs and exposure to high doses of radiation. Even more distressing is that fortunate survivors are generally left with life-long cognitive disabilities. A new medical approach is desperately needed. Stem cells, with their natural ability to seek out brain tumors, could be used to accurately deliver therapy directly to the cancer sparing normal tissues for suppression of tumor growth. Despite exciting initial reports, clinical potency of stem cell therapy in animal brain tumor models has to date proven disappointing. Attempts to extrapolate the animal study results to humans are stymied by the fact that stem cells are heterogeneous, resulting in differences in their efficacy. Indeed, therapeutic success relies on an effective strategy to select for a stem cell sub-population within some particular stage of the development at which they are competitive and capable of targeting brain tumors. To improve this during developmental path, concept of a 'therapeutic window' is proposed. The "therapeutic window" for stem cells or more specifically a "biochemical therapeutic window" can be determined from biochemical assays and a "biological therapeutic window" from biological assays or even a molecular window for genetic description. Taken together, we can use selective processes to generate more effective stem cells to treat cancers as is clearly needed today. PMID: 20528752 [PubMed - as supplied by publisher] | | |
| MR-based attenuation correction for hybrid PET-MR brain imaging systems using deformable image registration.
June 10, 2010 at 8:04 AM
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| | MR-based attenuation correction for hybrid PET-MR brain imaging systems using deformable image registration. Med Phys. 2010 May;37(5):2101-9 Authors: Schreibmann E, Nye JA, Schuster DM, Martin DR, Votaw J, Fox T PURPOSE: Realization of combined positron emission tomography (PET)--magnetic resonance (MR) scanners has the potential to significantly change healthcare and revolutionize clinical practice as it allows, simultaneously, visualization of molecular imaging and anatomical imaging. PET-MR, acquired in one imaging study, will likely become the advanced imaging modality of choice for neurological studies, certain forms of cancer, stroke, and the emerging study of stem cell therapy. A challenge toward the implementation and operation of combined PET-MR scanners is that attenuation corrections maps are not directly available due to space and cost constraints. This article presents a method to obtain accurate patient-specific PET attenuation coefficients maps in head imaging by warping an atlas computed tomography (CT) data set to the patient-specific MR data set using a deformable registration model. METHODS: A multimodality optical flow deformable model has been developed that establishes a voxel-to-voxel correspondence between the CT atlas and patient MR images. Once the mapping is established, the atlas is warped with the deformation field obtained by the registration to create a simulated CT image study that matches the patient anatomy, which could be used for attenuation correction. RESULTS: To evaluate the accuracy of the deformable-based attenuation correction, 17 clinical brain tumor cases were studied using acquired MR-CT images. A simulated CT was compared to the patient's true CT to assess geometrical accuracy of the deformation module as well as voxel-to-voxel comparison of Hounsfield units (HUs). In all cases, mapping from the atlas CT to the individual MR was achieved with geometrical accuracy as judged using quantitative inspection tools. The mean distance between simulated and true CT external contour and bony anatomy was 1.26 and 2.15 mm, respectively. In terms of HU unit comparison, the mean voxel-to-voxel difference was less than 2 HU for all cases. CONCLUSIONS: Attenuation correction for hybrid PET-MR scanners was easily achieved by individualizing an atlas CT to the MR data set using a deformable model without requiring user interaction. The method provided clinical accuracy while eliminating the need for an additional CT scan for PET attenuation correction. PMID: 20527543 [PubMed - in process] | | |
| Electrospun Alginate Nanofibers with Controlled Cell Adhesion for Tissue Engineering.
June 10, 2010 at 6:45 AM
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| | Electrospun Alginate Nanofibers with Controlled Cell Adhesion for Tissue Engineering. Macromol Biosci. 2010 Jun 9; Authors: Jeong SI, Krebs MD, Bonino CA, Khan SA, Alsberg E Alginate, a natural polysaccharide that has shown great potential as a cell scaffold for the regeneration of many tissues, has only been nominally explored as an electrospun biomaterial due to cytotoxic chemicals that have typically been used during nanofiber formation and crosslinking. Alginate cannot be electrospun by itself and is often co-spun with poly(ethylene oxide) (PEO). In this work, a cell adhesive peptide (GRGDSP) modified alginate (RA) and unmodified alginate (UA) were blended with PEO at different concentrations and blending ratios, and then electrospun to prepare uniform nanofibers. The ability of electrospun RA scaffolds to support human dermal fibroblast cell attachment, spreading, and subsequent proliferation was greatly enhanced on the adhesion ligand-modified nanofibers, demonstrating the promise of this electrospun polysaccharide material with defined nanoscale architecture and cell adhesive properties for tissue regeneration applications. PMID: 20533533 [PubMed - as supplied by publisher] | | |
| Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction.
June 10, 2010 at 6:45 AM
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| | Different assembly of type IV collagen on hydrophilic and hydrophobic substrata alters endothelial cells interaction. Eur Cell Mater. 2010;19:262-272 Authors: Coelho NM, González-GarcÃa C, Planell JA, Salmerón-Sánchez M, Altankov G Considering the structural role of type IV collagen (Col IV) in the assembly of the basement membrane (BM) and the perspective of mimicking its organization for vascular tissue engineering purposes, we studied the adsorption pattern of this protein on model hydrophilic (clean glass) and hydrophobic trichloro(octadecyl)silane (ODS) surfaces known to strongly affect the behavior of other matrix proteins. The amount of fluorescently labeled Col IV was quantified showing saturation of the surface for concentration of the adsorbing solution of about 50mug/ml, but with approximately twice more adsorbed protein on ODS. AFM studies revealed a fine - nearly single molecular size - network arrangement of Col IV on hydrophilic glass, which turns into a prominent and growing polygonal network consisting of molecular aggregates on hydrophobic ODS. The protein layer forms within minutes in a concentration-dependent manner. We further found that human umbilical vein endothelial cells (HUVEC) attach less efficiently to the aggregated Col IV (on ODS), as judged by the significantly altered cell spreading, focal adhesions formation and the development of actin cytoskeleton. Conversely, the immunofluorescence studies for integrins revealed that the fine Col IV network formed on hydrophilic substrata is better recognized by the cells via both alpha1 and alpha2 heterodimers which support cellular interaction, apart from these on hydrophobic ODS where almost no clustering of integrins was observed. PMID: 20533192 [PubMed - as supplied by publisher] | | |
| Preparation and physical properties of a novel biocompatible porcine corneal acellularized matrix.
June 10, 2010 at 6:45 AM
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| | Preparation and physical properties of a novel biocompatible porcine corneal acellularized matrix. In Vitro Cell Dev Biol Anim. 2010 Jun 9; Authors: Shao Y, Quyang L, Zhou Y, Tang J, Tan Y, Liu Q, Lin Z, Yin T, Qiu F, Liu Z This study was to investigate the stability, physico-mechanical property and biocompatibility of porcine corneal acellularized matrix (PCAM) that was prepared using human sera treatment to decellularize corneas. The stability (the rate of biodegradation) and physico-mechanical property (water uptake, density, and porosity) of PCAM were not compromised, compared with porcine fresh cornea matrix (PFCM, p > 0.05). The contact and extract cytotoxicity tests with human corneal epithelial cells and human keratocytes showed that PCAM has a good biocompatibility ex vivo and no cytotoxic effect. These results present the ability to create safety scaffolds that function as cornea grafts and provide a novel experimental approach for the study of cornea tissue engineering using acellular porcine cornea. PMID: 20532994 [PubMed - as supplied by publisher] | | |
| The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls.
June 10, 2010 at 6:45 AM
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| | The fabrication of PLGA microvessel scaffolds with nano-patterned inner walls. Biomed Microdevices. 2010 Jun 8; Authors: Wang GJ, Lin YC, Hsu SH Poly (lactic-co-glycolic acid) (PLGA) is one of the most commonly used biodegradable, biocompatible materials. Nanostructured PLGA has immense potential for application in tissue engineering. In this article we discuss a novel approach for the fabrication of PLGA microvessel scaffolds with nanostructured inner walls. In this novel nano-patterning approach, the thermal reflow technique is first adapted to fabricate a semi-cylindrical photoresist master mold. A thin film of titanium and a thin film of aluminum are sputtered in sequence on the semi-cylindrical microvessel network. Aluminum foil anodization is then executed to transform the aluminum thin film into a porous anodic aluminum oxide (AAO) film. During the casting process a PLGA solution is cast on the AAO film to build up semi-cylindrical PLGA microstructures with nanostructured inner walls after which inductive coupled plasma (ICP) is implemented to assist bonding of the two PLGA structures. The result is the building of a network of microchannels with nano-patterned inner walls. Bovine endothelial cells (BECs) are carefully cultured in the scaffold via semi-dynamic seeding for 7 days. Observations show that the BECs grew more separately in a nano-patterned microvessel scaffold than they did in a smooth surface scaffold. PMID: 20532635 [PubMed - as supplied by publisher] | | |
| Efficient Cell-Seeding into Scaffolds Improves Bone Formation.
June 10, 2010 at 6:45 AM
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| | Efficient Cell-Seeding into Scaffolds Improves Bone Formation. J Dent Res. 2010 Jun 8; Authors: Hasegawa T, Miwa M, Sakai Y, Niikura T, Lee SY, Oe K, Iwakura T, Kurosaka M, Komori T Bone marrow stromal cells (BMSCs)/beta-tricalcium phosphate (beta-TCP) composites have attracted a great deal of attention in bone tissue engineering. If more effective bone regeneration is to be achieved, efficient cell-seeding systems need to be clarified. In this study, we investigated the number of cells contained in composites, and the in vitro/vivo osteogenic differentiation capacity of composites using 4 conventional systems of seeding rat BMSCs into beta-TCP: soak, low-pressure, pipette, and syringe systems. The highest number of cells was contained in the composites from the syringe group. Moreover, after two-week osteogenic induction in vitro, the composites in the syringe group exhibited the highest osteogenic potential, which continued at 8 weeks after subcutaneous implantation in vivo. Our results indicated that efficient and appropriate cell-seeding could improve in vitro/vivo bone formation in composites and thus make a potential clinical contribution to successful bone tissue engineering. Abbreviations: BMSCs, bone marrow stromal cells; beta-TCP, beta-tricalcium phosphate; S-D, Sprague-Dawley; kPa, kilopascal; ALP, alkaline phosphatase; N, Newton; DNA, deoxyribonucleic acid; OCN, osteocalcin; ANOVA, analysis of variance; PLSD, protected least-significant difference; and HE, hematoxylin and eosin. PMID: 20530727 [PubMed - as supplied by publisher] | | |
| Keratinocyte growth factor phage model peptides can promote epidermal cell proliferation without tumorigenic effect.
June 10, 2010 at 6:45 AM
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| | Keratinocyte growth factor phage model peptides can promote epidermal cell proliferation without tumorigenic effect. Chin Med J (Engl). 2010 May;123(9):1195-200 Authors: Zong XL, Jiang DY, Wang JC, Liu JL, Liu ZZ, Cai JL BACKGROUND: Keratinocyte growth factor (KGF) significantly influences epithelial wound healing. The aim of this study was to isolate KGF phage model peptides from a phage display 7-mer peptide library to evaluate their effect on promoting epidermal cell proliferation. METHODS: A phage display 7-mer peptide library was screened using monoclonal anti-human KGF antibody as the target. Enzyme linked immunosorbent assay (ELISA) was performed to select monoclonal phages with good binding activity. DNA sequencing was done to find the similarities of model peptides. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, immunofluorescence assay and quantitative real-time PCR analysis were employed to evaluate the effect of the phage model peptides on epidermal cells. RESULTS: Thirty-three out of fifty-eight (56.9%) of the isolated monoclonal phages exhibited high binding activity by ELISA. Ten of fifteen obtained phage model peptides were similar to KGF or epidermal growth factor (EGF). MTT assay data showed that four (No. 1 - 4) of the ten phage model peptides could promote epidermal cell proliferation. The expression of keratinocyte growth factor receptor (KGFR) mRNA in the KGF control group and the two phage model peptide groups (No. 1 and No. 2) increased. Expression of c-Fos mRNA and c-Jun mRNA in the KGF control group increased, but did not increase in the four phage model peptide groups (No.1 - 4). CONCLUSION: Four phage model peptides isolated from the phage display 7-mer peptide library can safely promote epidermal cell proliferation without tumorigenic effect. PMID: 20529562 [PubMed - in process] | | |
| Smart biomaterials - regulating cell behavior through signaling molecules.
June 10, 2010 at 6:45 AM
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| | Smart biomaterials - regulating cell behavior through signaling molecules. BMC Biol. 2010;8(1):59 Authors: Mieszawska AJ, Kaplan DL ABSTRACT : Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC Biology, we review how spatial and temporal control of signaling molecules in a matrix material regulates cellular responses for tissue-specific applications.See research article http://www.biomedcentral.com/1741-7007/8/57. PMID: 20529238 [PubMed - in process] | | |
| Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction.
June 10, 2010 at 6:45 AM
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| | Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction. Tissue Eng Part A. 2010 Jun 9; Authors: Turner NJ, Yates AJ, Weber DJ, Qureshi IR, Beer Stolz D, Gilbert TW, Badylak SF The prevailing dogma in tissue engineering is cell-centric. One shortcoming of this approach is the failure to provide the implanted cells with a suitable in vivo microenvironment that promotes tissue reconstruction. Extracellular matrix (ECM)-based scaffolds provide a 3-dimensional microenvironment that can promote constructive and functional tissue remodeling rather than inflammation and scarring even in the absence of any implanted cells. The objective of this study was to determine the ability of an ECM-based scaffold to facilitate functional restoration of the distal gastrocnemius musculotendinous junction in a canine model following complete resection of the tissue. Within 6 months, vascularized, innervated skeletal muscle which was similar to normal muscle tissue had formed at the ECM-scaffold implantation site. This neo-tissue generated 48% of the contractile force of contralateral musculotendinous junction and represents the first report of de-novo formation of contractile, vascularized and innervated skeletal muscle in-situ following significant tissue loss. PMID: 20528669 [PubMed - as supplied by publisher] | | |
| Controlled cell seeding methodologies: a first step towards clinically relevant bone tissue engineering strategies.
June 10, 2010 at 6:45 AM
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| | Controlled cell seeding methodologies: a first step towards clinically relevant bone tissue engineering strategies. Tissue Eng Part C Methods. 2010 Jun 9; Authors: Impens SL, Chen Y, Mullens S, Luyten FP, Schrooten J The repair of large and complex bone defects could be helped by a cell based bone tissue engineering (TE) strategy. A reliable and consistent cell seeding methodology is a mandatory step in bringing bone TE into the clinic. However, optimization of the cell seeding step is only relevant when it can be reliably evaluated. The cell seeding efficiency (CSE) plays a fundamental role herein. Results showed that cell lysis and the definition used to determine the CSE, played a key role in quantifying the CSE. The definition of CSE should therefore be consistent and unambiguous. The study of the influence of five drop seeding related parameters within the studied test conditions showed that (i) the cell density and (ii) the seeding vessel did not significantly affect the CSE, whereas (iii) the volume of seeding medium to free scaffold volume ratio (MFR), (iv) the seeding time and (v) the scaffold morphology did. Prolonging the incubation time increased the CSE, up to a plateau value at 4 hours, while increasing the MFR or permeability by changing the morphology of the scaffolds significantly reduced the CSE. These results confirm that cell seeding optimization is needed and that an evidence based selection of the seeding conditions is favored. PMID: 20528665 [PubMed - as supplied by publisher] | | |
| Simple modular bioreactors for tissue engineering: a system for characterization of oxygen gradients, hMSC differentiation, and pre-vascularization.
June 10, 2010 at 6:45 AM
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| | Simple modular bioreactors for tissue engineering: a system for characterization of oxygen gradients, hMSC differentiation, and pre-vascularization. Tissue Eng Part C Methods. 2010 Jun 9; Authors: Lovett M, Rockwood DN, Baryshyan A, Kaplan DL Large-scale tissue engineering is limited by nutrient perfusion and mass transport limitations, especially oxygen diffusion, which restrict construct development to smaller than clinically relevant dimensions and limit the ability for in vivo integration. The goal of this work was to develop a modular approach to tissue engineering, where scaffold and tissue size, transport issues, and surgical implantation in vivo are considered from the outset. Human mesenchymal stem cells (hMSCs) were used as the model cell type, as their differentiation has been studied for several different cell lineages and often with conflicting results. Changes in the expression profiles of hMSCs differentiated under varied oxygen tensions are presented, demonstrating tissue-specific oxygen requirements for both adipogenic (20% O2) and chondrogenic (5% O2) differentiation. Oxygen and nutrient transport were enhanced by developing a bioreactor system for perfusing hMSC-seeded collagen gels using porous silk tubes, resulting in enhanced oxygen transport and cell viability within the gels. These systems are simple to use and scaled for versatility, to allow for the systematic study of relationships between cell content, oxygen and cell function. The data may be combined with oxygen transport modeling to derive minimally-sized modular units for construction of clinically-relevant tissue engineered constructs, a generic strategy that may be employed for vascularized target tissues. PMID: 20528664 [PubMed - as supplied by publisher] | | |
| Solving cell infiltration limitations of electrospun nanofiber meshes for tissue engineering applications.
June 10, 2010 at 6:45 AM
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| | Solving cell infiltration limitations of electrospun nanofiber meshes for tissue engineering applications. Nanomedicine (Lond). 2010 Jun;5(4):539-554 Authors: Guimarães A, Martins A, Pinho ED, Faria S, Reis RL, Neves NM Aim: Utilize the dual composition strategy to increase the pore size and solve the low cell infiltration capacity on random nanofiber meshes, an intrinsic limitation of electrospun scaffolds for tissue engineering applications. Materials & methods: Polycaprolactone and poly(ethylene oxide) solutions were electrospun simultaneously to obtain a dual composition nanofiber mesh. Selective dissolution of the poly(ethylene oxide) nanofiber fraction was performed. The biologic performance of these enhanced pore size nanofibrous structures was assessed with human osteoblastic cells. Results: The electrospun nanofiber meshes, after the poly(ethylene oxide) dissolution, showed statistically significant larger pore sizes when compared with polycaprolactone nanofiber meshes with a similar polycaprolactone volume fraction. This was also confirmed by interferometric optical profilometry. Using scanning electron microscopy and laser scanning confocal microscopy, it was observed that osteoblastic cells could penetrate into the nanofibrous structure and migrate into the opposite and unseeded side of the mesh. Conclusion: An electrospun mesh was created with sufficient pore size to allow cell infiltration into its structure, thus resulting in a fully populated construct appropriate for 3D tissue engineering applications. PMID: 20528450 [PubMed - as supplied by publisher] | | |
| In vivo evaluation of mixtures of uncultured freshly-isolated adipose-derived stem cells and demineralized bone matrix for bone regeneration in a rat critically-sized calvarial defect model.
June 10, 2010 at 6:45 AM
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| | In vivo evaluation of mixtures of uncultured freshly-isolated adipose-derived stem cells and demineralized bone matrix for bone regeneration in a rat critically-sized calvarial defect model. Stem Cells Dev. 2010 Jun 7; Authors: Rhee SC, Ji YH, Dhong ES, Park SH, Yoon ES Background: Although many studies have suggested that human adipose tissue contains pluripotent stem cells, a few reports are available on Stromal Vascular Fraction (SVF). In the present study, we evaluated the bone formation capacities of SVF. We implanted uncultured freshly-isolated adipose-derived stem cells com-bined with demineralized bone matrix to induce bone regeneration in a critically-sized rat calvarial defect model. Materials and Methods: We used demineralized bone matrix (DBX(R)) and/or P (L/DL) LA [Poly (70L-lactide-co-30DL-lactide) Co Polymer P (L/DL) LA] as a scaffold. Fifty white rats were randomized to 5 dif-ferent groups (n=10): 1) Control, 2) Group DBM, 3) Group DBM+SVF, 4) Group DBM+PLA, 5) Group DBM+PLA+SVF. After acquiring SVF, an 8-mm critically-sized calvarial defect was made in each rat. Spe-cimens were harvested at 8 weeks post-implantation and evaluated radiographically and histologically. New bone formation was qualified by H&E staining and by anti-osteocalcin antibody (OC4-30) immunostaining of calvarial sections. Amounts of mineralization were determined by radiodensitometric analysis. Results: In gross appearance, Group DBM+SVF and Group DBM+PLA+SVF showed more abundant bone formation than the other groups. Radiodensitometric evaluations revealed that significant inter-group differ-ences were observed according to the Kruskal-Wallis (Rank) test (p= 0.030<0.05). The five groups show dif-ferent amounts of filling of bone defects (Control group: 13.48%, Group DBM: 39.94% Group DBM+SVF: 57.69%, Group DBM+PLA: 24.86%, Group DBM+PLA+SVF: 42.75%). Histological evaluation revealed there was abundant new bone formation in Group DBM+SVF and Group DBM+PLA+SVF. Conclusions: It was found that undifferentiated adipose-derived stem cells in the form of SVF induced new bone formation in rat calvarial defects. Accordingly, SVF offers a practical, promising candidate for regenera-tive tissue engineering or cell-based therapy. PMID: 20528145 [PubMed - as supplied by publisher] | | |
| Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells.
June 10, 2010 at 6:45 AM
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| | Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells. J Biomech. 2010 Mar 22;43(5):920-6 Authors: Buckley CT, Vinardell T, Thorpe SD, Haugh MG, Jones E, McGonagle D, Kelly DJ Articular cartilage has a poor intrinsic capacity for self-repair. The advent of autologous chondrocyte implantation has provided a feasible method to treat cartilage defects. However, the associated drawbacks with the isolation and expansion of chondrocytes from autologous tissue has prompted research into alternative cell sources such as mesenchymal stem cells (MSCs) which have been found to exist in the bone marrow as well as other joint tissues such as the infrapatellar fat pad (IFP), synovium and within the synovial fluid itself. In this work we assessed the chondrogenic potential of IFP-derived porcine cells over a 6 week period in agarose hydrogel culture in terms of mechanical properties, biochemical content and histology. It was found that IFP cells underwent robust chondrogenesis as assessed by glycosaminoglycan (1.47+/-0.22% w/w) and collagen (1.44+/-0.22% w/w) accumulation after 42 days of culture. The 1Hz dynamic modulus of the engineered tissue at this time point was 272.8 kPa (+/-46.8). The removal of TGF-beta3 from culture after 21 days was shown to have a significant effect on both the mechanical properties and biochemical content of IFP constructs after 42 days, with minimal increases occurring from day 21 to day 42 without continued supplementation of TGF-beta3. These findings further strengthen the case that the IFP may be a promising cell source for putative cartilage repair strategies. PMID: 20005518 [PubMed - indexed for MEDLINE] | | |
| Directing bone marrow-derived stromal cell function with mechanics.
June 10, 2010 at 6:45 AM
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| | Directing bone marrow-derived stromal cell function with mechanics. J Biomech. 2010 Mar 22;43(5):807-17 Authors: Potier E, Noailly J, Ito K Because bone marrow-derived stromal cells (BMSCs) are able to generate many cell types, they are envisioned as source of regenerative cells to repair numerous tissues, including bone, cartilage, and ligaments. Success of BMSC-based therapies, however, relies on a number of methodological improvements, among which better understanding and control of the BMSC differentiation pathways. Since many years, the biochemical environment is known to govern BMSC differentiation, but more recent evidences show that the biomechanical environment is also directing cell functions. Using in vitro systems that aim to reproduce selected components of the in vivo mechanical environment, it was demonstrated that mechanical loadings can affect BMSC proliferation and improve the osteogenic, chondrogenic, or myogenic phenotype of BMSCs. These effects, however, seem to be modulated by parameters other than mechanics, such as substrate nature or soluble biochemical environment. This paper reviews and discusses recent experimental data showing that despite some knowledge limitation, mechanical stimulation already constitutes an additional and efficient tool to drive BMSC differentiation. PMID: 19962149 [PubMed - indexed for MEDLINE] | | |
| Impaired Cell Surface Expression of HLA-B Antigens on Mesenchymal Stem Cells and Muscle Cell Progenitors.
June 10, 2010 at 6:23 AM
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| | Impaired Cell Surface Expression of HLA-B Antigens on Mesenchymal Stem Cells and Muscle Cell Progenitors. PLoS One. 2010;5(5):e10900 Authors: Isa A, Nehlin JO, Sabir HJ, Andersen TE, Gaster M, Kassem M, Barington T HLA class-I expression is weak in embryonic stem cells but increases rapidly during lineage progression. It is unknown whether all three classical HLA class-I antigens follow the same developmental program. In the present study, we investigated allele-specific expression of HLA-A, -B, and -C at the mRNA and protein levels on human mesenchymal stem cells from bone marrow and adipose tissue as well as striated muscle satellite cells and lymphocytes. Using multicolour flow cytometry, we found high cell surface expression of HLA-A on all stem cells and PBMC examined. Surprisingly, HLA-B was either undetectable or very weakly expressed on all stem cells protecting them from complement-dependent cytotoxicity (CDC) using relevant human anti-B and anti-Cw sera. IFNgamma stimulation for 48-72 h was required to induce full HLA-B protein expression. Quantitative real-time RT-PCR showed that IFNgamma induced a 9-42 fold increase of all six HLA-A,-B,-C gene transcripts. Interestingly, prior to stimulation, gene transcripts for all but two alleles were present in similar amounts suggesting that post-transcriptional mechanisms regulate the constitutive expression of HLA-A,-B, and -C. Locus-restricted expression of HLA-A, -B and -C challenges our current understanding of the function of these molecules as regulators of CD8(+) T-cell and NK-cell function and should lead to further inquiries into their expression on other cell types. PMID: 20531935 [PubMed - as supplied by publisher] | | |
| Mesenchymal Stem Cells: New Approaches for the Treatment of Neurological Diseases.
June 10, 2010 at 6:23 AM
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| | Mesenchymal Stem Cells: New Approaches for the Treatment of Neurological Diseases. Curr Stem Cell Res Ther. 2010 Jun 9; Authors: Momin EN, Mohyeldin A, Zaidi HA, Vela G, Quiñones-Hinojosa A Cellular therapies represent a new frontier in the treatment of neurological disease. Mesenchymal stem cells (MSCs), which can be harvested from bone marrow, adipose tissue, and umbilical cord blood, among many other sources, possess several qualities which may be used to treat diseases of the central nervous system. MSCs migrate to sites of malignancy, a property which may be used for the treatment of brain cancer. MSCs possess immunosuppressive properties, which may be used for the treatment of neurological disorders with an inflammatory etiology. Finally, MSCs restore injured neural tissue, a property which may be used for the treatment of neural injury. Approximately 23 clinical trials have been completed to date, with many more ongoing, and all have been listed in this review. The long-term safety of MSC-based therapies is not well established, and continues to be one major limitation to clinical translation. More broadly, only a small minority of clinical trials have employed rigorous designs that include prospective randomization, patients from multiple centers, clinically-relevant and reproducible endpoints, and adequate long-term follow-up. These limitations must be addressed before MSCs can enter widespread clinical use. Nevertheless, MSCs represent a promising new approach to treating diseases of the central nervous system that are traditionally associated with morbid outcomes. With additional pre-clinical and clinical studies that focus on their potential benefits as well as dangers, MSCs may one day find translation to clinical use in the setting of neurological disease. PMID: 20528757 [PubMed - as supplied by publisher] | | |
| LPA rescues ER stress-associated apoptosis in hypoxia and serum deprivation-stimulated mesenchymal stem cells.
June 10, 2010 at 6:09 AM
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| | LPA rescues ER stress-associated apoptosis in hypoxia and serum deprivation-stimulated mesenchymal stem cells. J Cell Biochem. 2010 Jun 7; Authors: Li Z, Wei H, Liu X, Hu S, Cong X, Chen X Poor viability of transplanted mesenchymal stem cells (MSCs) in the infracted heart has limited their therapeutic efficacy in cardiac repair after myocardial infarction. We previously demonstrated that hypoxia and serum deprivation (hypoxia/SD) induced mitochondria-dependent apoptosis in MSCs, while lysophosphatidic acid (LPA) could almost completely block this apoptotic process. However, the role of endoplasmic reticulum (ER) stress and its upstream signaling events in hypoxia/SD-induced MSC apoptosis remain largely unknown. Here we found that hypoxia/SD-induced MSC apoptosis was associated with ER stress, as shown by the induction of CHOP expression and procaspase-12 cleavage, while the effects were abrogated by LPA treatment, suggesting ER stress is also a target of LPA. Furthermore, hypoxia/SD induced p38 activation, inhibition of which resulted in decreases of apoptotic cells, procaspase-12 cleavage and mitochondrial cytochrome c release that function in parallel in MSC apoptosis. Unexpectedly, p38 inhibition enhanced hypoxia/SD-induced CHOP expression. Interestingly, p38 activation, a common process mediating various biological effects of LPA, was inhibited by LPA in this study, and the regulation of p38 pathway by LPA was dependent on LPA(1/3)/Gi/ERK1/2 pathway-mediated MKP-1 induction but independent of PI3K/Akt pathway. Collectively, our findings indicate that ER stress is a target of LPA to antagonize hypoxia/SD-induced MSC apoptosis, and the modulation of mitochondrial and ER stress-associated apoptotic pathways by LPA is at least partly dependent on LPA(1/3)/Gi/ERK/MKP-1 pathway-mediated p38 inhibition. This study may provide new anti-apoptotic targets for elevating the viability of MSCs for therapeutic potential of cardiac repair. J. Cell. Biochem. (c) 2010 Wiley-Liss, Inc. PMID: 20533299 [PubMed - as supplied by publisher] | | |
| Transplantation of Umbilical Cord Blood Stem Cells for Treating Spinal Cord Injury.
June 10, 2010 at 6:09 AM
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| | Transplantation of Umbilical Cord Blood Stem Cells for Treating Spinal Cord Injury. Stem Cell Rev. 2010 Jun 8; Authors: Park DH, Lee JH, Borlongan CV, Sanberg PR, Chung YG, Cho TH Spinal cord injury (SCI) develops primary and secondary damage to neural tissue and this often results in permanent disability of the motor and sensory functions. However, there is currently no effective treatment except methylprednisolone, and the use of methylprednisolone has also been questioned due to its moderate efficacy and the drug's downside. Regenerative medicine has remarkably developed since the discovery of stem cells, and many studies have suggested the potential of cell-based therapies for neural injury. Especially, the therapeutic potential of human umbilical cord blood cells (hUCB cells) for intractable neurological disorders has been demonstrated using in vitro and vivo models. The hUCB cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Their ability to produce several neurotropic factors and to modulate immune and inflammatory reactions has also been noted. Recent evidence has emerged suggesting alternative pathways of graft-mediated neural repair that involve neurotrophic effects. These effects are caused by the release of various growth factors that promote cell survival, angiogenesis and anti-inflammation, and this is all aside from a cell replacement mechanism. In this review, we present the recent findings on the stemness properties and the therapeutic potential of hUCB as a safe, feasible and effective cellular source for transplantation in SCI. These multifaceted protective and restorative effects from hUCB grafts may be interdependent and they act in harmony to promote therapeutic benefits for SCI. Nevertheless, clinical studies with hUCB are still rare because of the concerns about safety and efficiency. Among these concerns, the major histocompatibility in allogeneic transplantation is an important issue to be addressed in future clinical trials for treating SCI. PMID: 20532836 [PubMed - as supplied by publisher] | | |
| Molecular genetic and bile acid profiles in 2 Japanese patients with 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase deficiency.
June 10, 2010 at 6:09 AM
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| | Molecular genetic and bile acid profiles in 2 Japanese patients with 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase deficiency. Pediatr Res. 2010 Jun 7; Authors: Mizuochi T, Kimura A, Ueki I, Takahashi T, Hashimoto T, Takao A, Seki Y, Takei H, Nittono H, Kurosawa T, Matsuishi T We report definitive diagnosis and effective chenodeoxycholic acid treatment of 2 Japanese children with 3beta-hydroxy-Delta-C27-steroid dehydrogenase/isomerase deficiency. Findings of cholestasis with normal serum gamma-glutamyltransferase activity and total bile acid concentration indicated the need for definitive bile acid analysis. Large amounts of 3beta-hydroxy-Delta-bile acids were detected by gas chromatography-mass spectrometry. HSD3B7 gene analysis using peripheral lymphocyte genomic DNA from the patients and their parents identified 4 novel mutations of the HSD3B7 gene in the patients. One had a homozygous mutation, 314delA; the other had compound heterozygous mutations: V132F, T149I, and 973_974insCCTGC. Interestingly, the second patient's mother had V132F and T149I mutations in 1 allele. Excessive 3beta-hydroxy-Delta-bile acids such as 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholenoic acids were detected in the first patient's urine; the second patient's urine contained large amounts of 3beta-hydroxy-5-cholenoic acid. Liver dysfunction in both patients decreased with ursodeoxycholic acid treatment, but unusual bile acids still were detected. Normalization of the patients' liver function and improvement of bile acid profiles occurred with chenodeoxycholic acid treatment. Thus, we found mutations in the HSD3B7 gene accounting for autosomal recessive neonatal cholestasis caused by 3beta-hydroxy-Delta-C27-steroid dehydrogenase/isomerase deficiency. Early neonatal diagnosis permits initiation of chenodeoxycholic acid treatment at this critical time, before the late cholestatic stage. ABBREVIATIONS:: PMID: 20531254 [PubMed - as supplied by publisher] | | | | 
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