Skin permeation studies of chromium species - Evaluation of a reconstructed human epidermis model.

A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of C

Rat Adipose Tissue-Derived Stem Cells Transplantation Attenuates Cardiac Dysfunction Post Infarction and Biopolymers Enhance Cell Retention

Background: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). Methodology/Principal Findings: (99m)Tc-labeled ASCs (1 x 10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. Conclusions: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[01/0009-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[05/54695-3]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)[04/06784-4]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[552324/20005-1]Ministerio da Ciencia e Tecnologia/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/Ministerio da Saude/Departamento Ciencia e Tecnologia (MCT/CNPq/MS/DECIT)[10120104096700]CNPq[141276/2004-5

Electrospun poly(d/l-lactide-co-l-lactide) hybrid matrix: a novel scaffold material for soft tissue engineering

Electrospinning is a long-known polymer processing technique that has received more interest and attention in recent years due to its versatility and potential use in the field of biomedical research. The fabrication of three-dimensional (3D) electrospun matrices for drug delivery and tissue engineering is of particular interest. In the present study, we identified optimal conditions to generate novel electrospun polymeric scaffolds composed of poly-d/l-lactide and poly-l-lactide in the ratio 50:50. Scanning electron microscopic analyses revealed that the generated poly(d/l-lactide-co-l-lactide) electrospun hybrid microfibers possessed a unique porous high surface area mimicking native extracellular matrix (ECM). To assess cytocompatibility, we isolated dermal fibroblasts from human skin biopsies. After 5 days of in vitro culture, the fibroblasts adhered, migrated and proliferated on the newly created 3D scaffolds. Our data demonstrate the applicability of electrospun poly(d/l-lactide-co-l-lactide) scaffolds to serve as substrates for regenerative medicine applications with special focus on skin tissue engineering

Mesenchymal Stem Cell Responses to Bone-Mimetic Electrospun Matrices Composed of Polycaprolactone, Collagen I and Nanoparticulate Hydroxyapatite

The performance of biomaterials designed for bone repair depends, in part, on the ability of the material to support the adhesion and survival of mesenchymal stem cells (MSCs). In this study, a nanofibrous bone-mimicking scaffold was electrospun from a mixture of polycaprolactone (PCL), collagen I, and hydroxyapatite (HA) nanoparticles with a dry weight ratio of 50/30/20 respectively (PCL/col/HA). The cytocompatibility of this tri-component scaffold was compared with three other scaffold formulations: 100% PCL (PCL), 100% collagen I (col), and a bi-component scaffold containing 80% PCL/20% HA (PCL/HA). Scanning electron microscopy, fluorescent live cell imaging, and MTS assays showed that MSCs adhered to the PCL, PCL/HA and PCL/col/HA scaffolds, however more rapid cell spreading and significantly greater cell proliferation was observed for MSCs on the tri-component bone-mimetic scaffolds. In contrast, the col scaffolds did not support cell spreading or survival, possibly due to the low tensile modulus of this material. PCL/col/HA scaffolds adsorbed a substantially greater quantity of the adhesive proteins, fibronectin and vitronectin, than PCL or PCL/HA following in vitro exposure to serum, or placement into rat tibiae, which may have contributed to the favorable cell responses to the tri-component substrates. In addition, cells seeded onto PCL/col/HA scaffolds showed markedly increased levels of phosphorylated FAK, a marker of integrin activation and a signaling molecule known to be important for directing cell survival and osteoblastic differentiation. Collectively these results suggest that electrospun bone-mimetic matrices serve as promising degradable substrates for bone regenerative applications

Modeling pulmonary arterial hypertension using induced pluripotent stem cells

Heritable pulmonary arterial hypertension belongs to a group of pulmonary vascular diseases for which there is currently no cure other than a heart and lung transplantation. Increased endothelial and smooth muscle cell proliferation leads to vascular remodeling, resulting in increased blood pressure in the lungs which ultimately causes right heart failure. Understanding the molecular mechanisms implicated in the establishment and progression of pulmonary arterial hypertension is hampered due to a lack of disease models, including a limited availability of patient-derived cells and the low penetrance of BMPR2, the major disease-associated gene. Induced pluripotent stem cells provide a series of advantages for disease modeling that could potentially allow theses issues to be overcome. These include (1) a limitlessly self-renewing capacity that overcomes the restricted supply of cells from diseased patients, (2) an epigenome that has been wiped of pathogenic modifications which have accumulated during the disease process, (3) an amenability to gene editing which allows the introduction of specific pathogenic mutations in an otherwise isogenic background to facilitate the dissection of the precise contribution of disease-associated genetic mutations, and (4) the generation of isogenic cell, tissue, and organ-specific disease models

Double Bond Stereochemistry Influences the Susceptibility of Short‑Chain Isoprenoids and Polyprenols to Decomposition by Thermo‑Oxidation

Alcohols are common constituents of living cells. They are usually assigned a role in the adaptation of the cell to environmental stimuli, and this process might give rise to their oxidation by reactive oxygen species. Moreover, cellular isoprenoids may also undergo various chemical modifications resulting from the physicochemical treatment of the tissues, e.g., heating during food processing. Susceptibility of isoprenoid alcohols to heat treatment has not been studied in detail so far. In this study, isoprenoid alcohols differing in the number of isoprene units and geometry of the double bonds, β-citronellol, geraniol, nerol, farnesol, solanesol and Pren-9, were subjected to thermo-oxidation at 80 °C. Thermo-oxidation resulted in the decomposition of the tested short-chain isoprenoids as well as medium-chain polyprenols with simultaneous formation of oxidized derivatives, such as hydroperoxides, monoepoxides,diepoxides and aldehydes, and possible formation of oligomeric derivatives. Oxidation products were monitored by GC-FID, GC-MS, ESI-MS and spectrophotometric methods. Interestingly, nerol, a short-chain isoprenoid with a double bond in the cis (Z) configuration, was more oxidatively stable than its trans (E) isomer, geraniol. However, the opposite effect was observed for medium-chain polyprenols, since Pren-9 (di-trans-poly-cis-prenol) was more susceptible to thermo-oxidation than its all-trans isomer, solanesol. Taken together, these results experimentally confirm that both short- and long-chain polyisoprenoid alcohols are prone to thermo-oxidation