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195 results on '"Moldovan, Nicanor I."'

4. Anapedesis: Implications and Applications of Bio-Structural Robustness

Author

Moldovan, Nicanor I.

Subjects
Quantitative Biology - Other Quantitative Biology, Quantitative Biology - Cell Behavior
Abstract

Here we develop an approach to bio-structural robustness integrated with structure-function relationship in a unified conceptual and methodological framework, and envision its study using adequate computational and experimental methods. To distinguish this structural robustness from the abstract organizational robustness of systems, we call it anapedesis, and define it as the scale-independent property of biological objects, from biomolecules to organisms, to deform and recover while minimizing and/or repairing the damage produced by stretch. We propose to study the consequences of deformation of biological objects closer to their structural and/or functional failure than previously considered relevant. We show that structural robustness is present as a basic principle in many facets of biomedicine: many pathological conditions may derive from the failure of molecules, cells and their higher-order assemblies to maintain robustness against deformation. Furthermore, structural robustness could have been the key selective criterion during pre-biotic evolution and afterwards, and its universality can be demonstrated by modeling using genetic algorithms. Thus, the specific investigation of bio-structural robustness as anapedesis could help the solving of fundamental problems of biology and medicine.

Published
2008

7. Of balls, inks and cages : hybrid biofabrication of 3D tissue analogs

Author

Moldovan, Nicanor I., Moldovan, Leni, Raghunath, Michael, Moldovan, Nicanor I., Moldovan, Leni, and Raghunath, Michael

Abstract

The overarching principle of three-dimensional (3D) bioprinting is the placing of cells or cell clusters in the 3D space to generate a cohesive tissue microarchitecture that comes close to in vivo characteristics. To achieve this goal, several technical solutions are available, generating considerable combinatorial bandwidth: (i) Support structures are generated first, and cells are seeded subsequently; (ii) alternatively, cells are delivered in a printing medium, so-called "bioink," that contains them during the printing process and ensures shape fidelity of the generated structure; and (iii) a "scaffold-free" version of bioprinting, where only cells are used and the extracellular matrix is produced by the cells themselves, also recently entered a phase of accelerated development and successful applications. However, the scaffold-free approaches may still benefit from secondary incorporation of scaffolding materials, thus expanding their versatility. Reversibly, the bioink-based bioprinting could also be improved by adopting some of the principles and practices of scaffold-free biofabrication. Collectively, we anticipate that combinations of these complementary methods in a "hybrid" approach, rather than their development in separate technological niches, will largely increase their efficiency and applicability in tissue engineering.

Published
2023

13. Vascular Patterning as Integrative Readout of Complex Molecular and Physiological Signaling by VESsel GENeration Analysis

Author

Moldovan Nicanor I, Alexander Pinhas, Susana B. Zanello, Corey A. Theriot, Mark Lagatuz, Miguel Martinho, Giovanni Taibbi, Toco Yuen Ping Chui, Patricia Parsons-Wingerter, Daniel J. Lindner, Ruchi J. Vyas, Maria B. Grant, Shiyin Lim, Nicole M. Jacobs, Krishnan Radhakrishnan, Mariana Dupont, Marina Predovic, Hans-Christian Reinecker, Nikunj C. Oza, Richard B Rosen, Mary B. Vickerman, David L. Kao, Hamed Valizadegan, and Gianmarco Vizzeri

Subjects
Models, Anatomic, 0301 basic medicine, Physiology, Angiogenesis, Basic fibroblast growth factor, Neovascularization, Physiologic, Inflammation, Vascular Remodeling, 030204 cardiovascular system & hematology, Biology, Article, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, law, Retinal Vein Occlusion, medicine, Animals, Humans, Computer Simulation, Angiogenic Proteins, 3D bioprinting, Retina, Diabetic Retinopathy, Neovascularization, Pathologic, Weightlessness, Bioprinting, Models, Cardiovascular, Retinal Vessels, Arteries, Biomarker (cell), Vascular endothelial growth factor, Fractals, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, chemistry, Printing, Three-Dimensional, Astronauts, Keratinocyte growth factor, medicine.symptom, Cardiology and Cardiovascular Medicine, Neuroscience, Software, Signal Transduction
Abstract

The molecular signaling cascades that regulate angiogenesis and microvascular remodeling are fundamental to normal development, healthy physiology, and pathologies such as inflammation and cancer. Yet quantifying such complex, fractally branching vascular patterns remains difficult. We review application of NASA’s globally available, freely downloadable VESsel GENeration (VESGEN) Analysis software to numerous examples of 2D vascular trees, networks, and tree-network composites. Upon input of a binary vascular image, automated output includes informative vascular maps and quantification of parameters such as tortuosity, fractal dimension, vessel diameter, area, length, number, and branch point. Previous research has demonstrated that cytokines and therapeutics such as vascular endothelial growth factor, basic fibroblast growth factor (fibroblast growth factor-2), transforming growth factor-beta-1, and steroid triamcinolone acetonide specify unique “fingerprint” or “biomarker” vascular patterns that integrate dominant signaling with physiological response. In vivo experimental examples described here include vascular response to keratinocyte growth factor, a novel vessel tortuosity factor; angiogenic inhibition in humanized tumor xenografts by the anti-angiogenesis drug leronlimab; intestinal vascular inflammation with probiotic protection by Saccharomyces boulardii, and a workflow programming of vascular architecture for 3D bioprinting of regenerative tissues from 2D images. Microvascular remodeling in the human retina is described for astronaut risks in microgravity, vessel tortuosity in diabetic retinopathy, and venous occlusive disease.

Published
2021

16. Role of heat shock factor-1 activation in the doxorubicin-induced heart failure in mice

Author

Vedam, Kaushik, Nishijima, Yoshinori, Druhan, Lawrence J., Khan, Mahmood, Moldovan, Nicanor I., Zweier, Jay L., and Ilangovan, Govindasamy

Subjects
Doxorubicin -- Dosage and administration, Doxorubicin -- Complications and side effects, Heart failure -- Risk factors, Heart failure -- Genetic aspects, Heart failure -- Research, Heat shock proteins -- Health aspects, Heat shock proteins -- Research, Messenger RNA -- Physiological aspects, Messenger RNA -- Research, Biological sciences
Abstract

Treating cancer patients with chemotherapeutics, such as doxorubicin (Dox), cause dilated cardiomyopathy and congestive heart failure because of oxidative stress. On the other hand, heat shock factor-1 (HSF-1), a transcription factor for heat shock proteins (Hsps), is also known to be activated in response to oxidative stress. However, the possible role of HSF-1 activation and the resultant Hsp25 in chemotherapeutic-induced heart failure has not been investigated. Using HSF-1 wild-type ([HSF-1.sup.+/+]) and knockout ([HSF-1.sup.-/-]) mice, we tested the hypothesis that activation of HSF-1 plays a role in the development of Dox-induced heart failure. Higher levels of Hsp25 and its phosphorylated forms were found in the failing hearts of Dox-treated [HSF-1.sup.+/+] mice. More than twofold increase in Hsp25 mRNA level was found in Dox-treated hearts. Proteomic analysis showed that there is accumulation and aggregation of Hsp25 in Dox-treated failing hearts. Additionally, Hsp25 was found to coimmunoprecipitate with p53 and vice versa. Further studies indicated that the Dox-induced higher levels of Hsp25 transactivated p53 leading to higher levels of the pro-apoptotic protein Bax, but other p53-related proteins remained unaltered. Moreover, [HSF-1.sup.-/-] mice showed significantly reduced Dox-induced heart failure and higher survival rate, and there was no change in Bax upon treating with Dox in [HSF-1.sup.-/-] mice. From these results we propose a novel mechanism for Dox-induced heart failure: increased expression of Hsp25 because of oxidant-induced activation of HSF-1 transactivates p53 to increase Bax levels, which leads to heart failure. heat shock proteins; oxidative stress; p53 doi: 10.1152/ajpheart.01047.2009.

Published
2010

21. Prospects for microtechnology and nanotechnology in bioengineering of replacement microvessels. (Advances in the Science of Pathology)

Author

Moldovan, Nicanor I. and Ferrari, Mauro

Subjects
Tissue engineering -- Research, Pathology, Molecular -- Research
Abstract

Context.--Due to its anticipated curative potential, therapeutic angiogenesis recently became a major preoccupation for the biomedical research community. Most of the related work reported to date employs either biochemical or genetic tools. Objective.--To identify opportunities for application of the current developments in microtechnology and nanotechnology to the field of therapeutic angiogenesis. Data Sources.--Survey of recent English-language literature on microvascular tissue engineering in the context of therapeutic angiogenesis. We include our results regarding the role played by microtopographical cues in the progression of angiogenesis, such as those produced during processing of the extracellular matrix by chronic inflammatory cells. Conclusion.--While notable accomplishments have been identified in the field of tissue engineering of larger vessels, reports on purposeful assembly of microvascular structures with the ability to be transferred in vivo by implantation are still scarce. Under these circumstances, we suggest the development of a new class of implantable biomedical microdevices, that is, "angiogenesis assist devices" (or "angiochips"), and we indicate some of their conceivable applications., Tissue engineering is a very promising and dynamic research field. Its applications currently vary from simple materials used as implants, molded to reproduce the geometry and/or the mechanical properties of [...]

Published
2002

22. Trends in genomic analysis of the cardiovascular system. (Advances in the Science of Pathology)

Author

Moldovan, Leni and Moldovan, Nicanor I.

Subjects
Cardiovascular diseases -- Genetic aspects, Cardiovascular system -- Physiological aspects
Abstract

Objective.--To evaluate the opportunities afforded cardiovascular medicine by the comprehensive and integrative approaches of genomics in cellular physiology. We present a meta-analysis of recently reported results obtained by means of high-throughput technologies (complementary DNA and oligonucleotide arrays, serial analysis of gene expression [SAGE]), as well as more traditional molecular biology approaches (real-time polymerase chain reaction, differential display, and others). Data Sources.--Newly published articles identified on PubMed and additional data provided by authors on-line (where available). Conclusions.--The impact of genomic analysis on cardiovascular research is already visible. New genes of cardiovascular interest have been discovered, while a number of known genes have been found to be changed in unexpected contexts. The patterns in the variation of expression of many genes correlate well with the models currently used to explain the pathogenesis of cardiovascular diseases. Much more work has yet to be done, however, for the full exploitation of the immense informative potential still dormant in the genomic technologies., The deciphering of the human genome presents the scientific community with an avalanche of information that needs to be sorted, interpreted, and used to our benefit. (1,2) To respond to [...]

Published
2002

26. Endothelial dysfunction in a murine model of mild hyperhomocyst(e)inemia

Author

Eberhardt, Robert T., Forgione, Marc A., Cap, Andre, Leopold, Jane A., Rudd, M. Audrey, Trolliet, Maria, Heydrick, Stanley, Stark, Rachel, Klings, Elizabeth S., Moldovan, Nicanor I., Yaghoubi, Mohammed, Goldschmidt-Clermont, Pascal J., Farber, Harrison W., Cohen, Richard, and Loscalzo, Joseph

Published
2000

33. Transcriptional Networks in Single Perivascular Cells Sorted from Human Adipose Tissue Reveal a Hierarchy of Mesenchymal Stem Cells

Author

Hardy, W. Reef, primary, Moldovan, Nicanor I., additional, Moldovan, Leni, additional, Livak, Kenneth J., additional, Datta, Krishna, additional, Goswami, Chirayu, additional, Corselli, Mirko, additional, Traktuev, Dmitry O., additional, Murray, Iain R., additional, Péault, Bruno, additional, and March, Keith, additional

Published
2017
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34. Actin grips: Circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells

Author

Jones, Desiree, primary, Park, DoYoung, additional, Anghelina, Mirela, additional, Pécot, Thierry, additional, Machiraju, Raghu, additional, Xue, Ruipeng, additional, Lannutti, John J., additional, Thomas, Jessica, additional, Cole, Sara L., additional, Moldovan, Leni, additional, and Moldovan, Nicanor I., additional

Published
2015
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35. A Module of Human Peripheral Blood Mononuclear Cell Transcriptional Network Containing Primitive and Differentiation Markers Is Related to Specific Cardiovascular Health Variables

Author

Moldovan, Leni, primary, Anghelina, Mirela, additional, Kantor, Taylor, additional, Jones, Desiree, additional, Ramadan, Enass, additional, Xiang, Yang, additional, Huang, Kun, additional, Kolipaka, Arunark, additional, Malarkey, William, additional, Ghasemzadeh, Nima, additional, Mohler, Peter J., additional, Quyyumi, Arshed, additional, and Moldovan, Nicanor I., additional

Published
2014
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40. Principles of the KenzanMethod for Robotic Cell Spheroid-Based Three-Dimensional Bioprinting*

Author

Moldovan, Nicanor I., Hibino, Narutoshi, and Nakayama, Koichi

Abstract

Bioprinting is a technology with the prospect to change the way many diseases are treated, by replacing the damaged tissues with live de novocreated biosimilar constructs. However, after more than a decade of incubation and many proofs of concept, the field is still in its infancy. The current stagnation is the consequence of its early success: the first bioprinters, and most of those that followed, were modified versions of the three-dimensional printers used in additive manufacturing, redesigned for layer-by-layer dispersion of biomaterials. In all variants (inkjet, microextrusion, or laser assisted), this approach is material (“scaffold”) dependent and energy intensive, making it hardly compatible with some of the intended biological applications. Instead, the future of bioprinting may benefit from the use of gentler scaffold-free bioassembling methods. A substantial body of evidence has accumulated, indicating this is possible by use of preformed cell spheroids, which have been assembled in cartilage, bone, and cardiac muscle-like constructs. However, a commercial instrument capable to directly and precisely “print” spheroids has not been available until the invention of the microneedles-based (“Kenzan”) spheroid assembling and the launching in Japan of a bioprinter based on this method. This robotic platform laces spheroids into predesigned contiguous structures with micron-level precision, using stainless steel microneedles (“kenzans”) as temporary support. These constructs are further cultivated until the spheroids fuse into cellular aggregates and synthesize their own extracellular matrix, thus attaining the needed structural organization and robustness. This novel technology opens wide opportunities for bioengineering of tissues and organs.

Published
2017
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45. Regulation of Adult Hematopoietic Stem Cells Fate for Enhanced Tissue-specific Repair

Author

Sengupta, Nilanjana, primary, Caballero, Sergio, additional, Sullivan, Sean M, additional, Chang, Lung-Ji, additional, Afzal, Aqeela, additional, Li Calzi, Sergio, additional, Kielczewski, Jennifer L, additional, Prabarakan, Sabrina, additional, Ellis, E Ann, additional, Moldovan, Leni, additional, Moldovan, Nicanor I, additional, Boulton, Michael E, additional, and Grant, Maria B, additional

Published
2009
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