New era of personalized medicine:Advanced therapy medicinal products in Europe

Advanced therapy medicinal products are human medical therapies based on genes,cells,or tissues,and due to their characteristics,they offer new innovative opportunities for the treatment of diseases and injuries,especially for diseases beyond the reach of traditional approaches.These therapies are at the forefront of innovation and have historically been very controversial,although in the last decade they have gained prominence while the number of new advanced therapies has increased every year.In this regard,despite the controversy they may generate,they are expected to dominate the market in the coming decades.Technologies based on advanced therapies are the present and future of medicine and bring us closer to the long-awaited precision medicine.Here we review the field as it stands today,with a focus on the molecular mechanisms that guided the different advanced therapies approved by the European Medicines Agency,their current status,and their legal approval.

Molecular pathogenesis and therapeutic strategies of human osteosarcoma

Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy regimens.Identifying the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic targets.Defects in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease phenotypes.As such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific aberrancies.Born out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical testing.They broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing agents.As new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than ever.In this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

Advances in the engineering of the outer blood-retina barrier:From in-vitro modelling to cellular therapy

The outer blood-retina barrier(oBRB),crucial for the survival and the proper functioning of the overlying retinal layers,is disrupted in numerous diseases affecting the retina,leading to the loss of the photoreceptors and ultimately of vision.To study the oBRB and/or its degeneration,many in vitro oBRB models have been developed,notably to investigate potential therapeutic strategies against retinal diseases.Indeed,to this day,most of these pathologies are untreatable,especially once the first signs of degeneration are observed.To cure those patients,a current strategy is to cultivate in vitro a mature oBRB epithelium on a custom membrane that is further implanted to replace the damaged native tissue.After a description of the oBRB and the related diseases,this review presents an overview of the oBRB models,from the simplest to the most complex.Then,we propose a discussion over the used cell types,for their relevance to study or treat the oBRB.Models designed for in vitro applications are then examined,by paying particular attention to the design evolution in the last years,the development of pathological models and the benefits of co-culture models,including both the retinal pigment epithelium and the choroid.Lastly,this review focuses on the models developed for in vivo implantation,with special emphasis on the choice of the material,its processing and its characterization,before discussing the reported pre-clinical and clinical trials.

Recent developments in regenerative ophthalmology

Regenerative medicine(RM)is one of the most promising disciplines for advancements in modern medicine,and regenerative ophthalmology(RO)is one of the most active fields of regenerative medicine.This review aims to provide an overview of regenerative ophthalmology,including the range of tools and materials being used,and to describe its application in ophthalmologic subspecialties,with the exception of surgical implantation of artificial tissues or organs(e.g.,contact lens,artificial cornea,intraocular lens,artificial retina,and bionic eyes)due to space limitations.In addition,current challenges and limitations of regenerative ophthalmology are discussed and future directions are highlighted.