The glycosaminoglycan-binding domain of PRELP acts as a cell type–specific NF-κB inhibitor that impairs osteoclastogenesis

The PRELP heparin sulfate–binding protein translocates to the nucleus, where it impairs NF-κB transcriptional activity, which in turn regulates bone homeostasis

Considerations in the Design of Non-Clinical Development Programmes to Support Non-Viral Genetically Modified Mesenchymal Stromal Cell Therapies

Due to their immune suppressive pharmacology, regenerative capacity, and immune privileged status, mesenchymal stromal cells (MSCs) are an attractive cell type to treat a variety of diseases. Genetically engineered MSCs are currently in non-clinical and clinical development for a wide range of applications including the delivery of pro-drugs and therapeutic proteins or modified to enhance their regenerative potential. Unmodified MSCs have been shown to have good safety profiles in clinical development. The introduction of exogenous transgenes introduces possible additional risks that need to be assessed in non-clinical studies prior to initiating clinical studies. The use of ex vivo non-viral genetic modification approaches potentially reduces the risks associated with viral vector transfection approaches, including the potential for cell transformation. This review provides an overview of the regulatory-compliant non-clinical proof-of-concept and safety studies required to take MSC-based gene therapy products from the bench to the clinic

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

Hepatocyte transplantation has emerged as an alternative to liver transplant for liver disease. Hepatocytes encapsulated in alginate microbeads have been proposed for the treatment of acute liver failure, as they are able to provide hepatic functions while the liver regenerates. Furthermore, they do not require immunosuppression, as the alginate protects the hepatocytes from the recipient's immune cells. Mesenchymal stromal cells are very attractive candidates for regenerative medicine, being able to differentiate into cells of the mesenchymal lineages and having extensive proliferative ability. When co-cultured with hepatocytes in two-dimensional cultures, they exert a trophic role, drastically improving hepatocytes survival and functions. In this study we aimed to (i) devise a high throughput system (HTS) to allow testing of a variety of different parameters for cell encapsulation and (ii) using this HTS, investigate whether mesenchymal stromal cells could have beneficial effects on the hepatocytes when co-encapsulated in alginate microbeads. Using our HTS platform, we observed some improvement of hepatocyte behavior with MSCs, subsequently confirmed in the low throughput analysis of cell function in alginate microbeads. Therefore, our study shows that mesenchymal stromal cells may be a good option to improve the function of hepatocytes microbeads. Furthermore, the platform developed may be used for HTS studies on cell encapsulation, in which several conditions (e.g., number of cells, combinations of cells, alginate modifications) could be easily compared at the same time

A New High Throughput Screening Platform for Cell Encapsulation in Alginate Hydrogel Shows Improved Hepatocyte Functions by Mesenchymal Stromal Cells Co-encapsulation

U ovom završnom radu pokušano je detaljno opisati sve faze nastanka jedrilice klase Dragon. Gradnja ovakve jedrilice je izuzetno kompleksna, teška, te joj izgradnja traje dugo. Opisana je izgradnja od samog početka, od nacrta, preko nabave potrebnog materijala i opreme, alata do krajnjeg bojanja i postavljanja jarbola. Svaka faza gradnje je zahtjevna, te treba puno vremena do završetka gradnje. Posebna pažnja se pridaje točnom mjerenju i nabavi potrebnog materijala, alata i potrebne opreme. Također je bitno osigurati prostor za gradnju, natkriveno skladište za materijal i opremu. Piljenje drva za rebra i kasnije za laminiranje jedrilice mora biti maksimalno precizno. Svaki element jedrilice je trebalo precizno i uredno napraviti, te u konačnici sve napravljeno spojiti i učvrstiti kako bi dobili čvrsto i stabilno plovilo. Jedrilica klase Dragon je vrlo ugodna za plovidbu, te su utrošeno vrijeme i novac ispunili svrhu