Lessons from the Embryo: an Unrejected Transplant and a Benign Tumor
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Lessons from the Embryo: an Unrejected Transplant and a Benign Tumor Alaleh Rezalotfi 1,2,3
&
Angelos Varotsos Vrynas 4 & Maryam Dehghanian 5
&
Nima Rezaei 2,6,7,8
Accepted: 15 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Embryogenesis is regarded the ‘miracle of life’, yet numerous aspects of this process are not fully understood. As the embryo grows in the mother’s womb, immune components, stem cells and microenvironmental cues cooperate among others to promote embryonic development. Evidently, these key players are frequently associated with transplantation failure and tumor growth. While the fields of transplantation and cancer biology do not overlap, both can be viewed from the perspective of an embryo. As an ‘unrejected transplant’ and a ‘benign tumor’, lessons from embryonic development may reveal features of transplants and tumors that have been overlooked. Therefore, eavesdropping at these natural complex events during pregnancy may inspire more durable approaches to arrest transplant rejection or cancer progression. Keywords Embryogenesis . stem cells . Transplant . Tumor . Fetal-inspired medicine
Introduction The fetus, despite being an allogeneic organism, is not immunologically rejected by the mother’s immune system [1], allowing it to fully develop [2]. While an immune balance is established between pro- and anti-inflammatory cues to ensure both the embryo’s and mother’s safety, these controlled responses are not applicable in organ transplantation. The main challenge is to suppress pharmaceutically the host immune system of organ recipients to ensure the long-term
survival of allografts, yet prolonged immune suppression brings perils to them [3]. To effectively blend in with the organism, both transplants and the embryo need to adapt to endogenous immune defenses. Rather frequently, transplantation failures can possibly be explained by triggered immune mechanisms [4] that are usually silent during successful pregnancy. Moreover, resembling the immunosuppressive environment of an embryo, tumor cells grow in a microenvironment [5] that favors anti-tumor immunity. Along with an immunosuppressive microenvironment,
Alaleh Rezalotfi, Angelos Varotsos Vrynas and Maryam Dehghanian contributed equally to this work. * Nima Rezaei [email protected] Alaleh Rezalotfi [email protected] Angelos Varotsos Vrynas [email protected] Maryam Dehghanian [email protected] 1
2
Department of Stem Cells and Developmental Biology, Cell Sciences Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
3
Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran
4
Department of Bioengineering, Imperial College London, London, UK
5
Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
6
Rese
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