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Vladimir Mironov

Publications and source records attributed to Vladimir Mironov.

At least 19 recordsLinked to original sources
PubMed2007

Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues.

Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues.

Adenoviridae↗
PubMed2006

The cyclin-dependent kinase inhibitor Orysa;KRP1 plays an important role in seed development of rice.

Kip-related proteins (KRPs) play a major role in the regulation of the plant cell cycle. We report the identification of five putative rice (Oryza sativa) proteins that share characteristic motifs with previously described plant KRPs. To investigate the function of KRPs in rice development, we generated transgenic plants overexpressing the Orysa;KRP1 gene. Phenotypic analysis revealed that overexpressed KRP1 reduced cell production during leaf development. The reduced cell production in the leaf meristem was partly compensated by an increased cell size, demonstrating the existence of a compensatory mechanism in monocot species by which growth rate is less reduced than cell production, through cell expansion. Furthermore, Orysa;KRP1 overexpression dramatically reduced seed filling. Sectioning through the overexpressed KRP1 seeds showed that KRP overproduction disturbed the production of endosperm cells. The decrease in the number of fully formed seeds was accompanied by a drop in the endoreduplication of endosperm cells, pointing toward a role of KRP1 in connecting endocycle with endosperm development. Also, spatial and temporal transcript detection in developing seeds suggests that Orysa;KRP1 plays an important role in the exit from the mitotic cell cycle during rice grain formation.

Amino Acid Sequence↗
PubMed2006

Research project: Charleston Bioengineered Kidney Project.

The goal of Charleston Bioengineered Kidney Project is to engineer a functional living human kidney suitable for surgical implantation using principles of directed tissue self-assembly and tissue fusion. This is a multidisciplinary project which incorporates multiple innovative bioengineering technologies and expertise from a broad spectrum of disciplines. The conceptual framework, engineering principles, design, potential cell source as well as the first preliminary data demonstrating the feasibility of the proposed Charleston Bioengineered Kidney Project are outlined. The potential challenges are described. Finally, the experts' opinion about the proposed project is also presented.

Animals↗
PubMed2006

Review: bioprinting: a beginning.

An increasing demand for directed assembly of biologically relevant materials, with prescribed three-dimensional hierarchical organizations, is stimulating technology developments with the ultimate goal of re-creating multicellular tissues and organs de novo. Existing techniques, mostly adapted from other applications or fields of research, are capable of independently meeting partial requirements for engineering biological or biomimetic structures, but their integration toward organ engineering is proving difficult. Inspired by recent developments in material transfer processes operating at all relevant length scales--from nano to macro--which are amenable to biological elements, a new research field of bioprinting and biopatterning has emerged. Here we present a short review regarding the framework, state of the art, and perspectives of this new field, based on the findings presented at a recent international workshop.

Biomimetics↗
PubMed2006

American Association of Anatomists meeting on regenerative medicine.

Several years ago, the American Association of Anatomists (AAA) launched an innovative mini-meeting format as part of their annual meeting. The AAA continued this tradition by sponsoring a 2-day mini-symposium as a part of its meeting at FASEB Experimental Biology, 2006 in San Francisco, CA, USA. This year, the mini-symposium was focused on the promising and rapidly developing field of 'regenerative medicine'. The mini-symposium on 'regenerative medicine' included four separate but thematically integrated sessions: stem cells for regenerative medicine; biomimetic matrices for regenerative medicine; endothelial-mesenchymal transformation in cardiovascular regenerative medicine; and tissue engineering technologies for regenerative medicine. The goal of these sessions was to identify progress and highlight new trends and directions in the evolving field of regenerative medicine. It was an exciting 2-day mini-symposium that reviewed the differential potential of embryonic and adult stem cells, their role in tissue turnover and possible applications in tissue regeneration; identified important evolving basic science issues, such as the role of endothelial-mesenchymal transformation and stem cell recruitment in cardiovascular regenerative medicine; and, finally, clearly demonstrated how understanding basic scientific principles can be translated into novel cell therapeutics and tissue engineering modalities. The workshop also demonstrated the multidisciplinary (speakers included stem cell and developmental biologists, chemical engineers, tissue engineers, biophysicists, mathematicians and surgeons) and international (speakers represented US, Japan, Canada, Switzerland and Korea) character of ongoing efforts in the area of regenerative medicine and stem cell biology, impressive progress in this field, and confirmed the strong potential for clinical translation of emerging regenerative medicine technologies.

Anatomy↗
PubMed2006

Cardiovascular tissue engineering I. Perfusion bioreactors: a review.

Tissue engineering is a fast-evolving field of biomedical science and technology with future promise to manufacture living tissues and organs for replacement, repair, and regeneration of diseased organs. Owing to the specific role of hemodynamics in the development, maintenance, and functioning of the cardiovascular system, bioreactors are a fundamental of cardiovascular tissue engineering. The development of perfusion bioreactor technology for cardiovascular tissue engineering is a direct sequence of previous historic successes in extracorporeal circulation techniques. Bioreactors provide a fluidic environment for tissue engineered tissue and organs, and guarantee their viability, maturation, biomonitoring, testing, storage, and transportation. There are different types of bioreactors and they vary greatly in their size, complexity, and functional capabilities. Although progress in design and functional properties of perfusion bioreactors for tissue engineered blood vessels, heart valves, and myocardial patches is obvious, there are some challenges and insufficiently addressed issues, and room for bioreactor design improvement and performance optimization. These challenges include creating a triple perfusion bioreactor for vascularized tubular tissue engineered cardiac construct; designing and manufacturing fluidics-based perfused minibioreactors; incorporation of systematic mathematical modeling and computer simulation based on computational fluid dynamics into the bioreactor designing process; and development of automatic systems of hydrodynamic regime control. Designing and engineering of built-in noninvasive biomonitoring systems is another important challenge. The optimal and most efficient perfusion and conditioning regime, which accelerates tissue maturation of tissue-engineered constructs also remains to be determined. This is a first article in a series of reviews on critical elements of cardiovascular tissue engineering technology describing the current status, unsolved problems, and challenges of bioreactor technology in cardiovascular tissue engineering and outlining future trends and developments.

Bioreactors↗
PubMed2005

Tannic acid mimicking dendrimers as small intestine submucosa stabilizing nanomordants.

Chemical stabilization resulting in increased resistance to proteolytic degradation is one of the approaches in prevention of post-implantational aneurysm development in decellularized natural vascular scaffolds. Recently, tannic acid (TA) and tannic acid mimicking dendrimers (TAMD) have been suggested as potential stabilization agents for collagen and elastin. The aim of this work was to determine the stabilizing effects of TAMD on decellularized natural scaffolds. Vascular scaffolds fabricated from small intestine submucosa (SIS) and SIS plane sheets (Cook Biotech Inc.) were used. The biomechanical properties of the SIS vascular graft segments treated with TA and TAMD were tested. The effect of TAMD treatment on resistance to proteolytic degradation was evaluated by measuring biomechanical properties of TAMD stabilized and non-stabilized SIS specimens after incubation in collagenase solution. It was shown that treatment with TA as well as with TAMD increased the strength of tubular SIS as well as their resistance to proteolytic biodegradation manifested by preservation of biomechanical properties after collagenase treatment. Transmission electron microscopy demonstrated that treatment with TAMD increased the periodical pattern typical of collagen fiber ultrastructure as a result of the "mordant" effect. The possible collagen cross-linking effect of TAMD on SIS was investigated by differential scanning calorimetry (DSC). The treatment with TAMD induced a small, but detectable cross-linking effect, suggesting that TAMD do not establish extensive covalent cross links within the extracellular matrix but rather interact with collagen, thus rendering SIS scaffolds more resistant to proteolytic degradation.

Aneurysm↗
PubMed2005

On the role of endothelial progenitor cells in tumor neovascularization.

The exact role that bone marrow (BM)-derived endothelial progenitor cells (EPCs) play in tumor neovascularization is heavily debated. We develop a quantitative three-compartment model with predictive power regarding the dynamics of tumorigenesis. There are two distinct processes by which tumor neovasculature can be built: angiogenesis is the formation of new blood vessels from preexisting vessels; vasculogenesis is the formation of new vessels by recruiting circulating EPCs. We show that vasculogenesis-driven and angiogenesis-driven tumors grow in different ways. (i) If angiogenesis is the prevailing process, then the tumor mass (and volume) will grow as a cubic power of time, and BM-derived EPCs will stay at a constant level. (ii) If vasculogenesis is the dominant process, then the tumor mass will be characterized by a linear growth in time, and the number of circulating EPCs (after possibly increasing to a maximum) will decrease to low levels. With this information, one can identify the "signature" of each of the processes in the observations of tumor growth and the dynamics of the relevant characteristics, such as the level of BM-derived EPCs. We show how our results can help explain some apparently contradictory experimental data. We also propose ways to couple this study with directed experiments to identify the exact role of vasculogenesis in tumor progression.

Blood Vessels↗
PubMed2005

Can routine commercial cord blood banking be scientifically and ethically justified?

BACKGROUND TO THE DEBATE: Umbilical cord blood--the blood that remains in the placenta after birth--can be collected and stored frozen for years. A well-accepted use of cord blood is as an alternative to bone marrow as a source of hematopoietic stem cells for allogeneic transplantation to siblings or to unrelated recipients; women can donate cord blood for unrelated recipients to public banks. However, private banks are now open that offer expectant parents the option to pay a fee for the chance to store cord blood for possible future use by that same child (autologous transplantation).

Blood Banks↗
PubMed2005

Fabrication of tubular tissue constructs by centrifugal casting of cells suspended in an in situ crosslinkable hyaluronan-gelatin hydrogel.

Achieving the optimal cell density and desired cell distribution in scaffolds is a major goal of cell seeding technologies in tissue engineering. In order to reach this goal, a novel centrifugal casting technology was developed using in situ crosslinkable hyaluronan-based (HA) synthetic extracellular matrix (sECM). Living cells were suspended in a viscous solution of thiol-modified HA and thiol-modified gelatin, a polyethyleneglycol diacrylate crosslinker was added, and a hydrogel was formed during rotation. The tubular tissue constructs consisting of a densely packed cell layer were fabricated with the rotation device operating at 2000 rpm for 10 min. The majority of cells suspended in the HA mixture before rotation were located inside the layer after centrifugal casting. Cells survived the effect of the centrifugal forces experienced under the rotational regime employed. The volume cell density (65.6%) approached the maximal possible volume density based on theoretical sphere packing models. Thus, centrifugal casting allows the fabrication of tubular constructs with the desired redistribution, composition and thickness of cell layers that makes the maximum efficient use of available cells. Centrifugal casting in this sECM would enable rapid fabrication of tissue-engineered vascular grafts, as well as other tubular and planar tissue-engineered constructs.

Animals↗
PubMed2005

Tuning the cell-cycle engine for improved plant performance.

Cell-cycle regulation plays a crucial role in organogenesis, morphogenesis, growth and differentiation and conceptually offers a means to design a next generation of crop plants that outperform traditionally bred ones. However, cell-cycle regulation involves a large, highly redundant, set of genes, which complicates unravelling of function in the context of a higher plant. Nevertheless, ten years of molecular cell-cycle research, primarily in the model plant Arabidopsis, have demonstrated its potential for altering plant development.

Arabidopsis↗
PubMed2005

The Second International Workshop on Bioprinting, Biopatterning and Bioassembly.

The Second International Workshop on Bioprinting, Biopatterning and Bioassembly was held at the Medical University of South Carolina (MUSC), located in the beautiful, historic city of Charleston. The workshop attracted > 50 participants from 10 different countries, including mechanical and chemical engineers, molecular, cell and developmental biologists, biophysicists, mathematicians, clinicians, humanists and artists. Bioprinting can be defined as computer-aided, automatic, layer-by-layer deposition, transfer and patterning of biologically relevant materials. The workshop goal was to gather the world's experts and leaders, present the latest results, assess future trends, explore new applications, and promote international collaborations and academic-industrial partnerships. The workshop demonstrated the multidisciplinary and global character of ongoing efforts in the development of bioprinting technology, galvanised an evolving community of bioprintists, and demonstrated feasibility as well as strong potential for a broad spectrum of applications of bioprinting technology. The Third International Workshop on Bioprinting, Biopatterning and Bioassembly is planned for Japan in 2006.

Bioethics↗
PubMed2004

Engineering biological structures of prescribed shape using self-assembling multicellular systems.

Self-assembly is a fundamental process that drives structural organization in both inanimate and living systems. It is in the course of self-assembly of cells and tissues in early development that the organism and its parts eventually acquire their final shape. Even though developmental patterning through self-assembly is under strict genetic control it is clear that ultimately it is physical mechanisms that bring about the complex structures. Here we show, both experimentally and by using computer simulations, how tissue liquidity can be used to build tissue constructs of prescribed geometry in vitro. Spherical aggregates containing many thousands of cells, which form because of tissue liquidity, were implanted contiguously into biocompatible hydrogels in circular geometry. Depending on the properties of the gel, upon incubation, the aggregates either fused into a toroidal 3D structure or their constituent cells dispersed into the surrounding matrix. The model simulations, which reproduced the experimentally observed shapes, indicate that the control parameter of structure evolution is the aggregate-gel interfacial tension. The model-based analysis also revealed that the observed toroidal structure represents a metastable state of the cellular system, whose lifetime depends on the magnitude of cell-cell and cell-matrix interactions. Thus, these constructs can be made long-lived. We suggest that spherical aggregates composed of organ-specific cells may be used as "bio-ink" in the evolving technology of organ printing.

Animals↗
PubMed2004

Organ printing: fiction or science.

Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops. According to Steinberg's differential adhesion hypothesis (DAH), this may be understood by assuming that cells are motile and tissues made of such cells possess an effective surface tension. Here we show that based on these properties three-dimensional cellular structures of prescribed shape can be constructed by a novel method: cell aggregate printing. Spherical aggregates of similar size made of cells with known adhesive properties were prepared. Aggregates were embedded into biocompatible gels. When the cellular and gel properties, as well as the symmetry of the initial configuration were appropriately adjusted the contiguous aggregates fused into ring-like organ structures. To elucidate the driving force and optimal conditions for this pattern formation, Monte Carlo simulations based on a DAH motivated model were performed. The simulations reproduced the experimentally observed cellular arrangements and revealed that the control parameter of pattern evolution is the gel-tissue interfacial tension, an experimentally accessible parameter.

Biocompatible Materials↗
PubMed2003

Cell and organ printing 2: fusion of cell aggregates in three-dimensional gels.

We recently developed a cell printer (Wilson and Boland, 2003) that enables us to place cells in positions that mimic their respective positions in organs. However, this technology was limited to the printing of two-dimensional (2D) tissue constructs. Here we describe the use of thermosensitive gels to generate sequential layers for cell printing. The ability to drop cells on previously printed successive layers provides a real opportunity for the realization of three-dimensional (3D) organ printing. Organ printing will allow us to print complex 3D organs with computer-controlled, exact placing of different cell types, by a process that can be completed in several minutes. To demonstrate the feasibility of this novel technology, we showed that cell aggregates can be placed in the sequential layers of 3D gels close enough for fusion to occur. We estimated the optimum minimal thickness of the gel that can be reproducibly generated by dropping the liquid at room temperature onto a heated substrate. Then we generated cell aggregates with the corresponding (to the minimal thickness of the gel) size to ensure a direct contact between printed cell aggregates during sequential printing cycles. Finally, we demonstrated that these closely-placed cell aggregates could fuse in two types of thermosensitive 3D gels. Taken together, these data strongly support the feasibility of the proposed novel organ-printing technology.

Animals↗
PubMed2003

Organ printing: computer-aided jet-based 3D tissue engineering.

Tissue engineering technology promises to solve the organ transplantation crisis. However, assembly of vascularized 3D soft organs remains a big challenge. Organ printing, which we define as computer-aided, jet-based 3D tissue-engineering of living human organs, offers a possible solution. Organ printing involves three sequential steps: pre-processing or development of "blueprints" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation. A cell printer that can print gels, single cells and cell aggregates has been developed. Layer-by-layer sequentially placed and solidified thin layers of a thermo-reversible gel could serve as "printing paper". Combination of an engineering approach with the developmental biology concept of embryonic tissue fluidity enables the creation of a new rapid prototyping 3D organ printing technology, which will dramatically accelerate and optimize tissue and organ assembly.

Artificial Organs↗
PubMed2003

Perfusion bioreactor for vascular tissue engineering with capacities for longitudinal stretch.

Arterial growth during embryonic vascular development is associated with longitudinal strain. The longitudinal strain is an important element of the embryonic vascular mechanical environment (EVME). Thus, a perfusion bioreactor for vascular tissue engineered constructs must include the functional capacity for longitudinal strain. To accomplish this goal, a perfusion bioreactor with the capacity for longitudinal strain was developed. The bioreactor includes two media perfusion systems: one for the inside perfusion and one for the outside perfusion of the cardiovascular engineered tubular construct (CETC). The watertight perfusion chamber allows periodic changing of longitudinal strain of the construct during mechanical conditioning. The range of the longitudinal strain is 0% to 200%. The biomechanical properties of the CETC are controlled by a pressure transducer and a digital TV camera. The pressure transducer and TV camera are connected to a computer. This allows the recording of a relationship between the radius of the VTEG and pressure in both static and dynamic regimens. This bioreactor can perform biomechanical conditioning with longitudinal strain.

Animals↗