title: Concise review: humanized models of tumor immunology in the 21st century: convergence of cancer research and tissue engineering.
abstract: Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to "make the model organism mouse more human." To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.
authors.affiliation: Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.|Orthopedic Center for Musculoskeletal Research, University of Wuerzburg, Koenig-Ludwig-Haus, Wuerzburg, Germany.
authors.forename: Boris Michael
authors.initials: BM
authors.lastname: Holzapfel
authors.affiliation: Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.|Department of Orthopedics, University of Regensburg, Asklepios Klinikum Bad Abbach, Bad Abbach, Germany.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Wagner
authors.affiliation: Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.
authors.forename: Laure
authors.initials: L
authors.lastname: Thibaudeau
authors.affiliation: Stem Cell Biology Group, Blood and Bone Diseases Program, Mater Research Institute, The University of Queensland, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Levesque
authors.affiliation: Regenerative Medicine, Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Brisbane, Queensland, Australia.|George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.|Institute for Advanced Study, Technical University Munich, Garching, Munich, Germany.
authors.forename: Dietmar Werner
authors.initials: DW
authors.lastname: Hutmacher
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D009369:Neoplasms / Q000628:therapy*; D044968:Regenerative Medicine / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods; D023822:Tissue Engineering / Q000379:methods; D057170:Translational Research, Biomedical
keywords: Adult hematopoietic stem cells; Adult stem cells; Bone; Bone marrow; CD34+; Humanized mice models; Stem cell transplantation; Stem cell-microenvironment interactions; Tissue regeneration