The pathology of solid organ xenotransplantation Purpose of review The use of genetically modified pigs has resulted in prolonged xenograft organ survival, overcoming the initial barriers that lead to hyperacute rejection and immediate loss of the graft. The purpose of the present review is to revisit the xenogeneic response and the pathologic changes in the xenograft organ in the context of recent publications of large animal studies that highlight existing challenges. Recent findings Transgenic modifications that have included complement regulatory proteins and coagulation regulatory proteins have prolonged xenograft survival in pig to nonhuman primate kidneys, livers, and hearts. Modifications of immunosuppressive regimens such as the addition of mTOR inhibition and costimulatory blockade have also led to better outcomes. Antibody-mediated rejection and thrombotic microangiopathy persist as primary challenges to the field and require further systematic exploration. Summary The efforts to overcome the natural antibody response to xenoantigens are largely sufficient. There is great opportunity for designing immunosuppression protocols and for detecting early coagulopathies, complement activation, and donor-specific antibody response. With graft survival prolongation, there is also a greater need to understand mechanisms and to enhance diagnostic tools for pathologic evaluation. Correspondence to Ivy A. Rosales, Immunopathology Research Laboratory, Massachusetts General Hospital, Boston, MA 02114, USA. Tel: +1-617-7260233; mobile: +1-617-4606211; e-mail: irosales@mgh.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Organs by design: can bioprinting meet self-organization? Purpose of review Engineering functional organs starting from stem or progenitor cells holds promise to address the urgent need for organ transplants. However, to date, the development of complex organ structures remains an open challenge. Recent findings Among multiple approaches to organ regeneration that are being investigated, two main directions can be identified, namely the patterned deposition of cells to impose specific structures, using bioprinting technologies, and (ii) the spontaneous development of organoids, according to principles of self-organization. In this review, we shortly describe the advantages and limitations of these paradigms and we discuss how they can synergize their positive features to better control and robustly develop organs from stem cells, toward organogenesis by design. Summary The outlined possibilities to bring together tools and concepts of bioprinting and self-organization will be relevant not only to generate implantable organs, but also to dissect fundamental mechanisms of organogenesis and to test therapeutic strategies in modeled pathological settings. Correspondence to Ivan Martin, Department of Biomedicine, University Hospital Basel, University of Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland. Tel: +41(0)61 2652384; e-mail: ivan.martin@usb.ch Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Xenotransplantation: the summit climb No abstract available