scholarly journals Regenerative properties of human extraembryonal organs in tissue engineering

2018 ◽  
Vol 20 (4) ◽  
pp. 192-198
Author(s):  
L I Kalyuzhnaya ◽  
O N Kharkevich ◽  
A A Schmidt ◽  
O V Protasov

The characteristics of the umbilical cord extracellular matrix are discussed relatively of their potential use for tissue engineering. The purpose of this review is to assess the current knowledge about using of homologous biomaterials with regenerative properties to create bioengineered structures. One of the most important components of tissue engineering - matrix (scaffold), resident cells can migrate, attach to it and function. Due to their structure, matrices should be easily integrated into the patient’s tissue and provide conditions for cell growth and differentiation. The cells that populate the matrix in the bioreactor before the transplantation of this construction, or resident cells recruited into the transplanted extracellular matrix), and cell- matrix interactions are absolutely necessary components of tissue engineering. Available commercial bioengineering products made from mammalian tissues have certain advantages and significant disadvantages due to the risks of immunological reactions and transmission of infectious agents. The transplantation of products from xenogenic materials is prohibited by law in the Russian Federation. The donor material is limited, receipt of human cadaver material requires a long period of legal registration, which has a detrimental effect on the biomaterial. Therefore, finding a suitable homologous biomaterial is ongoing. Due to the peculiarities of the embryonic phenotype, extraembryonic tissues have special biological properties, one of which is the scarless healing of wounds. Low immunogenicity, optimal mechanical properties of extracellular matrix, presence of cell adhesion molecules and growth factors promoting regeneration provide anti-inflammatory, anti-fibrotic, anti- scarring properties for tissue engineering structures from umbilical cord and amniotic membrane. Umbilical cord and amnion due to the availability and non-invasiveness of obtaining from healthy young donors are an excellent source of homologous biomaterial for extracting matrices, cells and hydrogels for tissue engineering and regenerative medicine.

2021 ◽  
Vol 11 ◽  
Author(s):  
Claire Deligne ◽  
Kim S. Midwood

Solid cancers such as breast tumors comprise a collection of tumor, stromal and immune cells, embedded within a network of tumor-specific extracellular matrix. This matrix is associated with tumor aggression, treatment failure, chemo- and radio-resistance, poor survival and metastasis. Recent data report an immunomodulatory role for the matrix in cancer, via the creation of niches that control the migration, localization, phenotype and function of tumor-infiltrating immune cells, ultimately contributing to escape of immune surveillance. Macrophages are crucial components of the immune infiltrate in tumors; they are associated with a poor prognosis in breast cancer and contribute to shaping the anti-tumor immune response. We and others have described how matrix molecules commonly upregulated within the tumor stroma, such as tenascin-C, fibronectin and collagen, exert a complex influence over macrophage behavior, for example restricting or enhancing their infiltration into the tumor, and driving their polarization towards or away from a pro-tumoral phenotype, and how in turn macrophages can modify matrix production in the tumor to favor tumor growth and metastasis. Targeting specific domains of matrix molecules to reinstate an efficient anti-tumor immune response, and effectively control tumor growth and spread, is emerging as a promising field offering a new angle for cancer therapy. Here, we review current knowledge on the interactions between tumor-associated macrophages and matrix molecules that occur within the tumor microenvironment of breast cancer, and discuss how these pathways can be targeted for new immunotherapies for hard to treat, desmoplastic tumors.


2020 ◽  
Vol 22 (1) ◽  
pp. 124-130
Author(s):  
L I Kalyuzhnaya ◽  
V E Chernov ◽  
A S Frumkina ◽  
S V Chebotarev ◽  
D A Zemlyanoy ◽  
...  

The development of tissue engineering is based on the use of the extracellular matrix as a construct to which cells migrate and attach for proliferation, differentiation, and long-term functioning. The preparation of the matrix is one of the most important tasks, since it must be non-immunogenic, have optimal mechanical properties, contain cell adhesion molecules and growth factors and degrade at the predicted time. The search for biomaterial for the manufacture of the matrix is limited by a number of circumstances. Tissue-specific for the matrix intravital biomaterial is limited, cadaveric is not acceptable due to age-related changes or diseases that reduce the regenerative capacity of tissues; synthetic materials lack cell adhesion molecules or are not degraded. The umbilical cord is an accessible homologous biomaterial of non- embryonic origin, preserving the features of the embryonic phenotype. The optimal method of decellularization of the Warton jelly of the human umbilical cord in the manufacture of a full-component cell-free matrix is substantiated. Umbilical cord decellularization was carried out using a detergent method with a 0.05% sodium dodecyl sulfate solution for 24 hours. The quality of the decellularization was evaluated microscopically by staining with fluorescent dye and quantification of nucleic acids. The gentle method used to remove cells from the Warton jelly tissue meets the existing criteria for the effectiveness of decellularization, since only single cells and a small amount of deoxyribonucleic acid remain in the processed biomaterial. The technique does not provide centrifugation at high speeds, in which glycosaminoglycans and proteoglycans are lost from the matrix, the enzymatic action that destroys fibrillar collagen structures, and non-physiological conditions of decellularization. The therapeutic success of tissue-engineering structures based on the extracellular matrix will depend not only on the bioactivity of the umbilical cord, but also on the safety of the composition, structure and mechanical characteristics of the matrix. Due to the availability and non-invasiveness of receiving from healthy young donors, provisional organs are an excellent source of homologous biomaterial for matrix production.


1996 ◽  
Vol 74 (6) ◽  
pp. 867-873 ◽  
Author(s):  
Elisabeth Strunck ◽  
Gunter Vollmer

The influence of extracellular matrix (ECM) on expression and function of integrins in carcinogenesis and differentiation is not well understood, but the importance of altered adhesion features for tumor development and progression is obvious. Integrins as versatile molecules are mainly responsible for mediating cell–matrix interactions and transmembrane signal transduction. They are capable of transducing outside-in signals from ECM components or conversely to organize the matrix by inside-out signaling. In the study presented here, we report that the reconstituted basement membrane, Matrigel™, which induces morphological and functional differentiation of the endometrial adenocarcinoma cell line HEC 1B(L), also regulates the expression of various forms of the integrin β4 subunit. Furthermore, we were able to identify full-length isoforms with and without an altered cytoplasmic domain as well as truncated forms. Our findings suggest a regulatory role of integrin β4 isoforms and fragments in the process of in vitro differentiation of HEC 1B(L).Key words: endometrium, tumor cells, differentiation, extracellular matrix, β4-integrin expression.


2001 ◽  
Vol 12 (5) ◽  
pp. 373-398 ◽  
Author(s):  
Bjorn Steffensen ◽  
Lari Häkkinen ◽  
Hannu Larjava

During wound-healing, cells are required to migrate rapidly into the wound site via a proteolytically generated pathway in the provisional matrix, to produce new extracellular matrix, and, subsequently, to remodel the newly formed tissue matrix during the maturation phase. Two classes of molecules cooperate closely to achieve this goal, namely, the matrix adhesion and signaling receptors, the integrins, and matrix-degrading and -processing enzymes, the matrix metalloproteinases (MMPs). There is now substantial experimental evidence that blocking key molecules of either group will prevent or seriously delay wound-healing. It has been known for some time now that cell adhesion by means of the integrins regulates the expression of MMPs. In addition, certain MMPs can bind to integrins or other receptors on the cell surface involved in enzyme activation, thereby providing a mechanism for localized matrix degradation. By proteolytically modifying the existing matrix molecules, the MMPs can then induce changes in cell behavior and function from a state of rest to migration. During wound repair, the expression of integrins and MMPs is simultaneously up-regulated. This review will focus on those aspects of the extensive knowledge of fibroblast and keratinocyte MMPs and integrins in biological processes that relate to wound-healing.


2016 ◽  
Vol 04 (01) ◽  
pp. 1640001 ◽  
Author(s):  
Ying Wan ◽  
Xing Li ◽  
Shenqi Wang

Biohybrid materials play an important role in tissue engineering, artificial organs and regenerative medicine due to their regulation of cell function through specific cell–matrix interactions involving integrins, mostly those of fibroblasts and myofibroblasts, and ligands on the matrix surface, which have become current research focus. In this paper, recent progress of biohybrid materials, mainly including main types of biohybrid materials, rapid prototype (RP) technique for construction of 3D biohybrid materials, was reviewed in detail; moreover, their applications in tissue engineering, artificial organs and regenerative medicine were also reviewed in detail. At last, we address the challenges biohybrid materials may face.


1996 ◽  
Vol 74 (6) ◽  
pp. 823-831 ◽  
Author(s):  
Anita E. Yu ◽  
Robert E. Hewitt ◽  
David E. Kleiner ◽  
William G. Stetler-Stevenson

Extracellular matrix (ECM) turnover is an event that is tightly regulated. Much of the coordinate (physiological) or discoordinate (pathological) degradation of the ECM is catalyzed by a class of proteases known as the matrix metalloproteinases (MMPs) or matrixins. Matrixins are a family of homologous Zn atom dependent endopeptidases that are usually secreted from cells as inactive zymogens. Net degradative activity in the extracellular environment is regulated by specific activators and inhibitors. One member of the matrixin family, gelatinase A, is regulated differently from other MMPs, suggesting that it may play a unique role in cell–matrix interactions, including cell invasion. The conversion from the 72 kDa progelatinase A to the active 62 kDa species may be a key event in the acquisition of invasive potential. This discussion reviews some recent findings on the cellular mechanisms involved in progelatinase A activation and, in particular, the role of tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and transmembrane containing metalloproteinases (MT-MMP) in this process.Key words: tissue inhibitors of metalloproteinases, metalloproteinase, gelatinases, extracellular matrix, activation.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Julie Williams ◽  
Sanlin Robinson ◽  
Babak Alaei ◽  
Kimberly Homan ◽  
Maryam Clausen ◽  
...  

Abstract Background and Aims Questions abound regarding the translation of in vitro 2D cell culture systems to the human setting. This is especially true of the kidney in which there is a complex hierarchical structure and a multitude of cell types. While it is well accepted that extracellular matrix plays a large part in directing cellular physiology emerging research has highlighted the importance of shear stresses and flow rates too. To fully recapitulate the normal gene expression and function of a particular renal cell type how important is it to completely reconstitute their in vivo surroundings? Method To answer this question, we have cultured proximal tubular (PT) epithelial cells in a 3-dimensional channel embedded within an engineered extracellular matrix (ECM) under physiological flow that is colocalised with an adjacent channel lined with renal microvascular endothelial cells that mimic a peritubular capillary. Modifications to the system were made to allow up to 12 chips to be run in parallel in an easily handleable form. After a period of maturation under continuous flow, both cell types were harvested for RNAseq analyses. RNA expression data was compared with cells cultured under static 2-dimensional conditions on plastic or the engineered ECM. Additionally, the perfusion of glucose through this 3D vascularised PT model has been investigated in the presence and absence of known diabetes modulating agents. Results PCA of RNAseq data showed that a) static non-coated, b) static matrix-coated and c) flow matrix-coated conditions separated into 3 distinct groups, while cell co-culture had less impact. Analysis of transcriptomic signatures showed that many genes were modulated by the matrix with additional genes influenced under flow conditions. Several of these genes, classified as transporters, are of particular importance when using this model to assess drug uptake and safety implications. Co-culture regulated some interesting genes, but fewer than anticipated. Preliminary experiments are underway to monitor glucose uptake and transport between tubules under different conditions. Conclusion We have developed a medium throughput system in which matrix and flow modulate gene expression. This system can be used to study the physiology of molecular cross-talk between cells. Ongoing analysis will further consider relevance to human physiology.


Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 844 ◽  
Author(s):  
Katarzyna Klimek ◽  
Grazyna Ginalska

Polymer scaffolds constitute a very interesting strategy for tissue engineering. Even though they are generally non-toxic, in some cases, they may not provide suitable support for cell adhesion, proliferation, and differentiation, which decelerates tissue regeneration. To improve biological properties, scaffolds are frequently enriched with bioactive molecules, inter alia extracellular matrix proteins, adhesive peptides, growth factors, hormones, and cytokines. Although there are many papers describing synthesis and properties of polymer scaffolds enriched with proteins or peptides, few reviews comprehensively summarize these bioactive molecules. Thus, this review presents the current knowledge about the most important proteins and peptides used for modification of polymer scaffolds for tissue engineering. This paper also describes the influence of addition of proteins and peptides on physicochemical, mechanical, and biological properties of polymer scaffolds. Moreover, this article sums up the major applications of some biodegradable natural and synthetic polymer scaffolds modified with proteins and peptides, which have been developed within the past five years.


1991 ◽  
Vol 2 (3) ◽  
pp. 369-387 ◽  
Author(s):  
Adele L. Boskey

The extracellular matrix of dentin consists of mineral (hydroxyapatite), collagen, and several noncollagenous matrix proteins. These noncollagenous matrix proteins may be mediators of cell-matrix interactions, matrix maturation, and mineralization. This review describes the current knowledge of the chemistry of mineral crystal formation in dentin with special emphasis on the roles of the dentin matrix proteins. The functions of some of these matrix proteins in the mineralization process have been deduced based on in vitro studies. Functions for others have been postulated based on analogy with some of the bone matrix proteins. Evidence suggests that several of these matrix proteins may have multiple effects on nucleation, crystal growth, and orientation of dentin hydroxyapatite.


2009 ◽  
Vol 87 (12) ◽  
pp. 996-1008 ◽  
Author(s):  
Leon Espira ◽  
Michael P. Czubryt

The cardiac extracellular matrix, far from being merely a static support structure for the heart, is now recognized to play central roles in cardiac development, morphology, and cell signaling. Recent studies have better shaped our understanding of the tremendous complexity of this active and dynamic network. By activating intracellular signal cascades, the matrix transduces myocardial physical forces into responses by myocytes and fibroblasts, affecting their function and behavior. In turn, cardiac fibroblasts and myocytes play active roles in remodeling the matrix. Coupled with the ability of the matrix to act as a dynamic reservoir for growth factors and cytokines, this interplay between the support structure and embedded cells has the potential to exert dramatic effects on cardiac structure and function. One of the clearest examples of this occurs when cell–matrix interactions are altered inappropriately, contributing to pathological fibrosis and heart failure. This review will examine some of the recent concepts that have emerged regarding exactly how the cardiac matrix mediates these effects, how our collective vision of the matrix has changed as a result, and the current state of attempts to pharmacologically treat fibrosis.


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