scholarly journals Enhanced Host Neovascularization of Prevascularized Engineered Muscle Following Transplantation into Immunocompetent versus Immunocompromised Mice

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1472 ◽  
Author(s):  
Luba Perry ◽  
Uri Merdler ◽  
Maria Elishaev ◽  
Shulamit Levenberg
Keyword(s):  
Tissue Engineering ◽  
Immune System ◽  
Animal Models ◽  
Three Dimensional ◽  
Intact Immune System ◽  
Engineered Tissue ◽  
Immunocompetent Mice ◽  
Immunocompromised Mice ◽  
Post Implantation ◽  
Advantageous Effect

Engineering of functional tissue, by combining either autologous or allogeneic cells with biomaterials, holds promise for the treatment of various diseases and injuries. Prevascularization of the engineered tissue was shown to enhance and improve graft integration and neovascularization post-implantation in immunocompromised mice. However, the neovascularization and integration processes of transplanted engineered tissues have not been widely studied in immunocompetent models. Here, we fabricated a three-dimensional (3D) vascularized murine muscle construct that was transplanted into immunocompetent and immunocompromised mice. Intravital imaging demonstrated enhanced neovascularization in immunocompetent mice compared to immunocompromised mice, 18 days post-implantation, indicating the advantageous effect of an intact immune system on neovascularization. Moreover, construct prevascularization enhanced neovascularization, integration, and myogenesis in both animal models. These findings demonstrate the superiority of implantation into immunocompetent over immunocompromised mice and, therefore, suggest that using autologous cells might be beneficial compared to allogeneic cells and subsequent immunosuppression. Taken together, these observations have the potential to advance the field of regenerative medicine and tissue engineering, ultimately reducing the need for donor organs and tissues.

scholarly journals A Customizable, Low-Cost Perfusion System for Sustaining Tissue Constructs

2018 ◽  
Vol 23 (6) ◽  
pp. 592-598
Author(s):  
Brian J. O’Grady ◽  
Jason X. Wang ◽  
Shannon L. Faley ◽  
Daniel A. Balikov ◽  
Ethan S. Lippmann ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Cell Viability ◽  
Large Scale ◽  
Low Cost ◽  
Three Dimensional ◽  
Tissue Scaffolds ◽  
Perfusion System ◽  
Pump System ◽  
Tissue Constructs ◽  
Engineered Tissue

The fabrication of engineered vascularized tissues and organs requiring sustained, controlled perfusion has been facilitated by the development of several pump systems. Currently, researchers in the field of tissue engineering require the use of pump systems that are in general large, expensive, and generically designed. Overall, these pumps often fail to meet the unique demands of perfusing clinically useful tissue constructs. Here, we describe a pumping platform that overcomes these limitations and enables scalable perfusion of large, three-dimensional hydrogels. We demonstrate the ability to perfuse multiple separate channels inside hydrogel slabs using a preprogrammed schedule that dictates pumping speed and time. The use of this pump system to perfuse channels in large-scale engineered tissue scaffolds sustained cell viability over several weeks.

Soft-Tissue Analogue Design and Tissue Engineering of Liver

MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 52-54 ◽  
Author(s):  
Prabhas V. Moghe
Keyword(s):  
Tissue Engineering ◽  
Health Care Cost ◽  
Three Dimensional ◽  
Cell Types ◽  
The United States ◽  
Tissue Loss ◽  
Tissue Type ◽  
Design Parameters ◽  
Immune Rejection ◽  
Engineered Tissue

Tissue engineering involves the application of physical and life sciences to develop functional substitutes for dysfunctional organs or tissue structures. From an engineering standpoint, tissues contain two basic components—the cells that are organized into proper units, and the material surrounding the cells, called the extracellular matrix (ECM). A third, frequently overlooked feature essential to the maintenance of the activity of the engineered tissue is the three-dimensional architecture of the cell-matrix composite.A comprehensive review of the scope and impact of tissue engineering has previously appeared. Tissue-engineered devices have the potential to reduce the annual health-care cost related to tissue loss and end-stage organ failure to the order of $400 billion, eight million invasive surgical procedures, and 65 million hospital days. A common approach to engineer a functional tissue is to place cells derived from a healthy organ or tissue type (identical or similar to the dysfunctional tissue/organ) on or within matrices analogous to host-tissue ECM. These systems can then be enclosed in appropriate membranes that isolate cells from immune rejection following implantation or can be transplanted directly with the administration of drugs that prevent the immune rejection. Another application of these systems is for extracorporeal (outside the patient's body) device support of a dysfunctional organ. In either instance, the success of the engineered tissue depends critically on the interactions of cells with the tissue analogues. The objective of this article is to outline the simplest matrix-design parameters to control these interactions. While organs are comprised of very different tissue types, for the sake of simplicity, this article is primarily pertinent to the tissue engineering of one major organ, the liver. The choice of this tissue type is intended to serve as a comprehensive generalization of many different cell types since in the diversity and complexity of its activities, the liver has few parallels. The development of an artificial liver is also critically awaited, as in the United States alone, 35,000 people, including the many wait listed for the exorbitant liver organ transplants ($300,000), die each year of chronic liver disorders. In many other countries, liver disease is the second leading cause of death.

Interleukin-2 toxicity.

1991 ◽  
Vol 9 (4) ◽  
pp. 694-704 ◽  
Author(s):  
J P Siegel ◽  
R K Puri
Keyword(s):  
Immune System ◽  
Animal Models ◽  
Interleukin 2 ◽  
Clinical Development ◽  
Adverse Outcomes ◽  
Intact Immune System ◽  
Systems Studies ◽  
Selection Of Patients ◽  
Selection Of

Because of the ability of interleukin-2 (IL-2) to support the proliferation and activation of numerous types of immunocompetent cells and to support the survival of adoptively transferred lymphocytes, there has been considerable interest in its use in the immunotherapy of malignancies. While studies to date have indicated that IL-2 has activity against some malignancies, considerable toxicity has also been observed. Careful prescreening and selection of patients and appropriate management of toxicity can minimize adverse outcomes. Studies of IL-2 effects have provided intriguing evidence of interactions of the immune/cytokine system with the neuroendocrine, cardiovascular, and other systems. Studies in animal models have demonstrated the central role of an intact immune system in mediating many toxicities of IL-2. Several adverse effects of IL-2 appear to be mediated by other cytokines whose production is induced by IL-2. Studies into the pathogenesis and manifestations of IL-2 toxicity have offered the hope of developing less toxic approaches to IL-2 therapy. Several lessons from the IL-2 experience are likely to be applicable in the clinical development of other cytokines.

scholarly journals Breathing life into engineered tissues using oxygen-releasing biomaterials

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Sanika Suvarnapathaki ◽  
Xinchen Wu ◽  
Darlin Lantigua ◽  
Michelle A. Nguyen ◽  
Gulden Camci-Unal
Keyword(s):  
Tissue Engineering ◽  
Muscle Regeneration ◽  
Three Dimensional ◽  
Organ Donors ◽  
Effective Solution ◽  
Engineered Tissues ◽  
Different Types ◽  
Oxygen Requirements ◽  
Post Implantation ◽  
Over Time

Abstract Engineering three-dimensional (3D) tissues in clinically relevant sizes have demonstrated to be an effective solution to bridge the gap between organ demand and the dearth of compatible organ donors. A major challenge to the clinical translation of tissue-engineered constructs is the lack of vasculature to support an adequate supply of oxygen and nutrients post-implantation. Previous efforts to improve the vascularization of engineered tissues have not been commensurate to meeting the oxygen demands of implanted constructs during the process of homogeneous integration with the host. Maintaining cell viability and metabolic activity during this period is imperative to the survival and functionality of the engineered tissues. As a corollary, there has been a shift in the scientific impetus beyond improving vascularization. Strategies to engineer biomaterials that encapsulate cells and provide the sustained release of oxygen over time are now being explored. This review summarizes different types of oxygen-releasing biomaterials, strategies for their fabrication, and approaches to meet the oxygen requirements in various tissue engineering applications, including cardiac, skin, bone, cartilage, pancreas, and muscle regeneration.

scholarly journals Microvascular Guidance: A Challenge to Support the Development of Vascularised Tissue Engineering Construct

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Irza Sukmana
Keyword(s):  
Tissue Engineering ◽  
Three Dimensional ◽  
Artificial Organ ◽  
Vascular Networks ◽  
Tissue Constructs ◽  
Future Challenges ◽  
Engineered Tissue ◽  
And Function ◽  
Tissue Construct

The guidance of endothelial cell organization into a capillary network has been a long-standing challenge in tissue engineering. Some research efforts have been made to develop methods to promote capillary networks inside engineered tissue constructs. Capillary and vascular networks that would mimic blood microvessel function can be used to subsequently facilitate oxygen and nutrient transfer as well as waste removal. Vascularization of engineering tissue construct is one of the most favorable strategies to overpass nutrient and oxygen supply limitation, which is often the major hurdle in developing thick and complex tissue and artificial organ. This paper addresses recent advances and future challenges in developing three-dimensional culture systems to promote tissue construct vascularization allowing mimicking blood microvessel development and function encounteredin vivo. Bioreactors systems that have been used to create fully vascularized functional tissue constructs will also be outlined.

HYDROXYAPATITE, ALGINATE, AND CHITOSAN FOR BONE SCAFFOLDS: SPECTROSCOPY STUDY

2016 ◽  
Vol 19 (2) ◽  
pp. 93-100
Author(s):  
Lalita El Milla
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Functional Groups ◽  
Bone Growth ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Tissue Engineering Scaffolds ◽  
Hydroxyapatite Powder ◽  
Materials Used

Scaffolds is three dimensional structure that serves as a framework for bone growth. Natural materials are often used in synthesis of bone tissue engineering scaffolds with respect to compliance with the content of the human body. Among the materials used to make scafffold was hydroxyapatite, alginate and chitosan. Hydroxyapatite powder obtained by mixing phosphoric acid and calcium hydroxide, alginate powders extracted from brown algae and chitosan powder acetylated from crab. The purpose of this study was to examine the functional groups of hydroxyapatite, alginate and chitosan. The method used in this study was laboratory experimental using Fourier Transform Infrared (FTIR) spectroscopy for hydroxyapatite, alginate and chitosan powders. The results indicated the presence of functional groups PO43-, O-H and CO32- in hydroxyapatite. In alginate there were O-H, C=O, COOH and C-O-C functional groups, whereas in chitosan there were O-H, N-H, C=O, C-N, and C-O-C. It was concluded that the third material containing functional groups as found in humans that correspond to the scaffolds material in bone tissue engineering.

In vitro Three Dimensional Scaffold-free Construct of Human Adipose-derived Stem Cells in Coculture with Endothelial Cells and Fibroblasts

2017 ◽  
Vol 68 (6) ◽  
pp. 1341-1344
Author(s):  
Grigore Berea ◽  
Gheorghe Gh. Balan ◽  
Vasile Sandru ◽  
Paul Dan Sirbu
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Endothelial Cells ◽  
Single Cell ◽  
Cell Line ◽  
Bone Repair ◽  
Umbilical Vein ◽  
Human Fibroblasts ◽  
Three Dimensional ◽  
Adipose Derived Stem Cells

Complex interactions between stem cells, vascular cells and fibroblasts represent the substrate of building microenvironment-embedded 3D structures that can be grafted or added to bone substitute scaffolds in tissue engineering or clinical bone repair. Human Adipose-derived Stem Cells (hASCs), human umbilical vein endothelial cells (HUVECs) and normal dermal human fibroblasts (NDHF) can be mixed together in three dimensional scaffold free constructs and their behaviour will emphasize their potential use as seeding points in bone tissue engineering. Various combinations of the aforementioned cell lines were compared to single cell line culture in terms of size, viability and cell proliferation. At 5 weeks, viability dropped for single cell line spheroids while addition of NDHF to hASC maintained the viability at the same level at 5 weeks Fibroblasts addition to the 3D construct of stem cells and endothelial cells improves viability and reduces proliferation as a marker of cell differentiation toward osteogenic line.

Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials

2020 ◽  
Vol 15 (3) ◽  
pp. 187-201 ◽  
Author(s):  
Sunil K. Dubey ◽  
Amit Alexander ◽  
Munnangi Sivaram ◽  
Mukta Agrawal ◽  
Gautam Singhvi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Immune System ◽  
Clinical Application ◽  
Cell Types ◽  
Patient Specific ◽  
Potential Strategy ◽  
Induced Pluripotent ◽  
Treat All ◽  
The Impact

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

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