Catherine Stavropoulos Giokas

Bio: Catherine Stavropoulos Giokas is an academic researcher from Academy of Athens. The author has contributed to research in topics: Umbilical artery & Wharton's jelly. The author has an hindex of 3, co-authored 5 publications receiving 19 citations.

Interplay between mesenchymal stromal cells and immune system: clinical applications in immune-related diseases

Abstract: Mesenchymal stromal cells (MSCs) are a mesodermal stem cell population, with known self-renewal and multilineage differentiation properties. In the last century, MSCs have been widely used in regenerative medicine and tissue engineering approaches. MSCs initially were isolated from bone marrow aspirates, but currently have been identified in a great number of tissues of the human body. Besides their utilization in regenerative medicine, MSCs possess significant immunoregulatory/immunosuppressive properties, through interaction with the cells of innate and adaptive immunity. MSCs can exert their immunomodulatory properties with either cell-cell contact or via paracrine secretion of molecules, such as cytokines, growth factors and chemokines. Of particular importance, the MSCs’ immunomodulatory properties are explored as promising therapeutic strategies in immune-related disorders, such as autoimmune diseases, graft versus host disease, cancer. MSCs may also have an additional impact on coronavirus disease-19 (COVID-19), by attenuating the severe symptoms of this disorder. Nowadays, a great number of clinical trials, of MSC-mediated therapies are evaluated for their therapeutic potential. In this review, the current knowledge on cellular and molecular mechanisms involved in MSC-mediated immunomodulation were highlighted. Also, the most important aspects, regarding their potential application in immune-related diseases, will be highlighted. The broad application of MSCs has emerged their role as key immunomodulatory players, therefore their utilization in many disease situations is full of possibilities for future clinical treatment.

Recellularization potential of small diameter vascular grafts derived from human umbilical artery

Abstract: BACKGROUND The primary therapeutic strategy in cardiovascular disease is the coronary artery bypass surgery, which in- volves the use of small diameter vascular grafts (<6 mm). Human umbilical arteries could be used as a source for the development of these grafts. OBJECTIVE The aim of this study was the decellularization of human umbilical arteries and the evaluation of their re- cellularization potential. METHODS Decellularization of human umbilical arteries was performed with a detergent based protocol. Histological analysis was performed in order to determine the effect of decellularization. Then, recellularization was performed by using two different approaches. The first approach was the dynamic seeding of human umbilical arteries with Mesenchymal Stromal Cells and the second approach involved the recellularization by using a bioreactor system. RESULTS Histological analysis showed the successful removal of cellular and nuclear materials from the umbilical arteries. In addition, successful recellularization of the vessels was observed with both approaches. CONCLUSION The results of this study indicated that human umbilical arteries could serve as an alternative material for the proper development of small diameter vascular grafts.

Vitrified Wharton's jelly tissue as a biomaterial for multiple tissue engineering applications.

Abstract: Wharton’s Jelly (WJ) tissue is a promising biomaterial, for tissue engineering applications. However, its preservation over a long period in order to be readily available needs further opti...

Re-Endothelialized Small Diameter Vascular Grafts Derived from Human Umbilical Arteries as Coronary Artery Substitutes

Abstract: Background: Primary therapeutic strategy in Cardiovascular Disease (CVD) is the coronary artery bypass. Damaged coronary vessels need to be replaced with small diameter vascular grafts. Tissue engineering has focused on the production of vascular grafts, although major adverse reactions such as graft calcification, low patency rate and lumen occlusion still exist. This study aimed to the development of re-endothelialized small diameter vascular grafts in order to avoid the aforementioned adverse reactions. Methods: Human umbilical arteries were isolated and decellularized. The evaluation of the decellularization process was assessed by histological analysis. In addition, differentiated Endothelial Cells (ECs) derived from Wharton’s Jelly Mesenchymal Stromal Cells (WJ-MSCs) were used for the re-endothelialization process. Results: Our results indicated the successful decellularization of the vessels. Specifically, human Umbilical Arteries (hUAs) were characterized by absence of cellular and nuclear materials, while their extracellular matrix retained intact. Differentiated ECs successfully expressed CD31, VEGF-A, VEGF-R, vWF, FLK-1 and were able to form capillary like structures when cultured in Matrigel. Finally, the re-endothelialization of the decellularized hUAs with the differentiated ECs was successful based on the results of indirect immunofluorescence. Conclusion: In conclusion, the hUAs is a very promising source for the production of small diameter vascular grafts that could be used as coronary artery substitutes.

Tissue-Engineered Grafts from Human Decellularized Extracellular Matrices: A Systematic Review and Future Perspectives

Abstract: Tissue engineering and regenerative medicine involve many different artificial and biologic materials, frequently integrated in composite scaffolds, which can be repopulated with various cell types. One of the most promising scaffolds is decellularized allogeneic extracellular matrix (ECM) then recellularized by autologous or stem cells, in order to develop fully personalized clinical approaches. Decellularization protocols have to efficiently remove immunogenic cellular materials, maintaining the nonimmunogenic ECM, which is endowed with specific inductive/differentiating actions due to its architecture and bioactive factors. In the present paper, we review the available literature about the development of grafts from decellularized human tissues/organs. Human tissues may be obtained not only from surgery but also from cadavers, suggesting possible development of Human Tissue BioBanks from body donation programs. Many human tissues/organs have been decellularized for tissue engineering purposes, such as cartilage, bone, skeletal muscle, tendons, adipose tissue, heart, vessels, lung, dental pulp, intestine, liver, pancreas, kidney, gonads, uterus, childbirth products, cornea, and peripheral nerves. In vitro recellularizations have been reported with various cell types and procedures (seeding, injection, and perfusion). Conversely, studies about in vivo behaviour are poorly represented. Actually, the future challenge will be the development of human grafts to be implanted fully restored in all their structural/functional aspects.

Vascular Tissue Engineering: Polymers and Methodologies for Small Caliber Vascular Grafts.

Abstract: Cardiovascular disease is the most common cause of death in the world. In severe cases, replacement or revascularization using vascular grafts are the treatment options. While several synthetic vascular grafts are clinically used with common approval for medium to large-caliber vessels, autologous vascular grafts are the only options clinically approved for small-caliber revascularizations. Autologous grafts have, however, some limitations in quantity and quality, and cause an invasiveness to patients when harvested. Therefore, the development of small-caliber synthetic vascular grafts (<5 mm) has been urged. Since small-caliber synthetic grafts made from the same materials as middle and large-caliber grafts have poor patency rates due to thrombus formation and intimal hyperplasia within the graft, newly innovative methodologies with vascular tissue engineering such as electrospinning, decellularization, lyophilization, and 3D printing, and novel polymers have been developed. This review article represents topics on the methodologies used in the development of scaffold-based vascular grafts and the polymers used in vitro and in vivo.

Effect of fluid dynamics on decellularization efficacy and mechanical properties of blood vessels.

Abstract: Decellularization of blood vessels is a promising approach to generate native biomaterials for replacement of diseased vessels. The decellularization process affects the mechanical properties of the vascular graft and thus can have a negative impact for in vivo functionality. The aim of this study was to determine how detergents under different fluid dynamics affects decellularization efficacy and mechanical properties of the vascular graft. We applied a protocol utilizing 1% TritonX, 1% Tributyl phosphate (TnBP) and DNase on porcine vena cava. The detergents were applied to the vessels under different conditions; static, agitation and perfusion with 3 different perfusion rates (25, 100 and 400 mL/min). The decellularized grafts were analyzed with histological, immunohistochemical and mechanical tests. We found that decellularization efficacy was equal in all groups, however the luminal ultrastructure of the static group showed remnant cell debris and the 400 mL/min perfusion group showed local damage and tearing of the luminal surface. The mechanical stiffness and maximum tensile strength were not influenced by the detergent application method. In conclusion, our results indicate that agitation or low-velocity perfusion with detergents are preferable methods for blood vessel decellularization.

Insights into Biomechanical and Proteomic Characteristics of Small Diameter Vascular Grafts Utilizing the Human Umbilical Artery.

Abstract: The gold standard vascular substitutes, used in cardiovascular surgery, are the Dacron or expanded polytetrafluoroethylene (ePTFE)-derived grafts. However, major adverse reactions accompany their use. For this purpose, decellularized human umbilical arteries (hUAs) may be proven as a significant source for the development of small diameter conduits. The aim of this study was the evaluation of a decellularization protocol in hUAs. To study the effect of the decellularization to the hUAs, histological analysis was performed. Then, native and decellularized hUAs were biochemically and biomechanically evaluated. Finally, broad proteomic analysis was applied. Histological analysis revealed the successful decellularization of the hUAs. Furthermore, a great amount of DNA was removed from the decellularized hUAs. Biomechanical analysis revealed statistically significant differences in longitudinal direction only in maximum stress (p < 0.013) and strain (p < 0.001). On the contrary, all parameters tested for circumferential direction exhibited significant differences (p < 0.05). Proteomic analysis showed the preservation of the extracellular matrix and cytoskeletal proteins in both groups. Proteomic data are available via ProteomeXchange with identifier PXD020187. The above results indicated that hUAs were efficiently decellularized. The tissue function properties of these conduits were well retained, making them ideal candidates for the development of small diameter vascular grafts.