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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Immunol.</journal-id>
<journal-title>Frontiers in Immunology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Immunol.</abbrev-journal-title>
<issn pub-type="epub">1664-3224</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fimmu.2024.1439832</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Immunology</subject>
<subj-group>
<subject>Editorial</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Editorial: Community series in progress of allo- and xeno-transplantation facilitating the initial xeno-kidney and islet clinical trials, volume II</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Mou</surname>
<given-names>Lisha</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
<xref ref-type="author-notes" rid="fn001">
<sup>*</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1199233"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ekser</surname>
<given-names>Burcin</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/1260106/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>Department of Endocrinology, Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People&#x2019;s Hospital</institution>, <addr-line>Shenzhen</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>MetaLife Lab, Shenzhen Institute of Translational Medicine, Health Science Center, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People&#x2019;s Hospital</institution>, <addr-line>Shenzhen</addr-line>, <country>China</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Division of Transplant Surgery, Department of Surgery, Indiana University School of Medicine</institution>, <addr-line>Indianapolis, IN</addr-line>, <country>United States</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>Edited and Reviewed by: Antoine Toubert, Universit&#xe9; Paris Cit&#xe9;, France</p>
</fn>
<fn fn-type="corresp" id="fn001">
<p>*Correspondence: Lisha Mou, <email xlink:href="mailto:lishamou@email.szu.edu.cn">lishamou@email.szu.edu.cn</email>
</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>13</day>
<month>06</month>
<year>2024</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1439832</elocation-id>
<history>
<date date-type="received">
<day>28</day>
<month>05</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>06</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2024 Mou and Ekser</copyright-statement>
<copyright-year>2024</copyright-year>
<copyright-holder>Mou and Ekser</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<related-article id="RA1" related-article-type="commentary-article" xlink:href="https://www.frontiersin.org/research-topics/54736/community-series-in-progress-of-allo--and-xeno-transplantation-facilitating-the-initial-xeno-kidney-and-islet-clinical-trials-volume-ii/articles" ext-link-type="uri">Editorial on the Research Topic <article-title>Community series in progress of allo- and xeno-transplantation facilitating the initial xeno-kidney and islet clinical trials, volume II</article-title>
</related-article>
<kwd-group>
<kwd>xenotransplantation</kwd>
<kwd>islet transplantation</kwd>
<kwd>kidney transplantation</kwd>
<kwd>genetically modified porcine endothelial cells</kwd>
<kwd>PD-L1 overexpression</kwd>
<kwd>genetic modifications in pigs</kwd>
<kwd>microenvironment in transplantation</kwd>
<kwd>hepatocyte microencapsulation</kwd>
</kwd-group>
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<ref-count count="0"/>
<page-count count="3"/>
<word-count count="769"/>
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<custom-meta-wrap>
<custom-meta>
<meta-name>section-in-acceptance</meta-name>
<meta-value>Alloimmunity and Transplantation</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<p>The advent of xenotransplantation has ushered in a new era of possibilities in addressing the severe organ shortage crisis. The current Research Topic in this volume of &#x201c;Progress of Allo- and Xeno-transplantation Facilitating the Initial Xeno-Kidney and Islet Clinical Trials&#x201d; offers a collection of pioneering studies that explore various facets of xenotransplantation, particularly focusing on kidney and islet transplantation. This editorial provides an overview of the contributing articles, highlighting their key findings and placing them within the broader context of transplantation research.</p>
<sec id="s1">
<label>1</label>
<title>Challenges and opportunities in the islet transplantation microenvironment</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2023.1293762">Chen et&#xa0;al.</ext-link> presented a comprehensive summary of the challenges and opportunities in the islet transplantation microenvironment. Their study underscores the importance of the microenvironment in determining transplantation outcomes and offers insights into potential strategies to improve islet graft survival with a focus on inflammatory cytokines, immune cells, and vascular endothelial cells.</p>
</sec>
<sec id="s2">
<label>2</label>
<title>Pancreatic islet transplantation: current advances and challenges</title>
<p>In a similar topic but with a different approach, <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1391504">Wang et&#xa0;al.</ext-link> provided a thorough review of the current advances and challenges in pancreatic islet transplantation. They discuss the issues related to islet sourcing, transplantation sites, and immune rejection. Their study highlights the feasibility of inducing stem cells to differentiate into &#x3b2;-like cells <italic>in vitro</italic> and explores the potential of porcine islets in addressing the shortage of islet donors.</p>
</sec>
<sec id="s3">
<label>3</label>
<title>Co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells</title>
<p>To improve the outcomes in xenotransplantation, <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2023.1217809">Cross-Najafi et&#xa0;al.</ext-link> investigated the co-expression of HLA-E and HLA-G on genetically modified porcine endothelial cells. Their findings demonstrated that the co-expression of HLA-E and HLA-G can significantly attenuate human NK cell-mediated degranulation, shedding light on more successful xenotransplantation outcomes.</p>
</sec>
<sec id="s4">
<label>4</label>
<title>Combined islet and kidney xenotransplantation for diabetic nephropathy</title>
<p>A mini-review by <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1351717">Eisenson et&#xa0;al.</ext-link> provided an update on the ongoing research in combined islet and kidney xenotransplantation for diabetic nephropathy. The authors highlighted the potential of this dual approach in addressing both diabetes and kidney failure, showcasing promising preliminary results with evidence from the published literature.</p>
</sec>
<sec id="s5">
<label>5</label>
<title>Human PD-L1 overexpression in porcine kidneys</title>
<p>In original research by <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1279050">Schmalkuche et&#xa0;al.</ext-link>, the effect of human PD-L1 overexpression in porcine kidneys has been explored. This interesting study showed that human PD-L1 genetic modification can reduce xenogeneic human T-cell immune responses, thus enhancing the viability of porcine kidneys in case of clinical xenotransplantation.</p>
</sec>
<sec id="s6">
<label>6</label>
<title>Genetically modified pigs targeting complement activation</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1383936">Sun et&#xa0;al.</ext-link> discussed the cutting-edge genetic modifications in pigs aimed at targeting complement activation, which has been a major barrier in xenotransplantation. Their study provides valuable insights into the genetic engineering techniques that can mitigate immune rejection.</p>
</sec>
<sec id="s7">
<label>7</label>
<title>Microenvironment and survival in kidney transplantation</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1379742">Huang et&#xa0;al.</ext-link> conducted a bibliometric analysis to examine the relationship between the microenvironment and survival in kidney transplantation. Their analysis identifies key trends and research hotspots, offering a roadmap for future studies in this critical area.</p>
</sec>
<sec id="s8">
<label>8</label>
<title>Advances in hepatocyte microencapsulation</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1385022">Wang et&#xa0;al.</ext-link> reviewed the advances in hepatocyte microencapsulation, focusing on selecting materials and preservation methods. Their&#xa0;comprehensive review highlights the progress made in enhancing&#xa0;the&#xa0;viability and functionality of encapsulated hepatocytes for transplantation.</p>
</sec>
<sec id="s9">
<label>9</label>
<title>Developments in kidney xenotransplantation</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2023.1242478">Xu and He</ext-link> presented a detailed overview of the developments in kidney xenotransplantation. Their study highlights the significant strides made in genetic modifications and immunosuppressive protocols, which are crucial for the success of clinical xenotransplantation.</p>
</sec>
<sec id="s10">
<label>10</label>
<title>Ethical and legislative advances in xenotransplantation</title>
<p>With his expertise over decades, <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1355609">Hawthorne</ext-link> discussed the ethical and legislative advances in xenotransplantation, with a main focus on cardiac xenotransplants. His paper emphasizes the importance of ethical considerations and regulatory frameworks in advancing xenotransplantation to clinical practice in a safe manner.</p>
</sec>
<sec id="s11">
<label>11</label>
<title>Anesthesia and surgery in kidney xenotransplantation</title>
<p>
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fimmu.2024.1386382">Zhang et&#xa0;al.</ext-link> explored the role of anesthesia and surgical techniques in advancing kidney xenotransplantation to clinical practice. Their study bridges the gap between preclinical and clinical practices, offering insights into optimizing surgical outcomes.</p>
<p>The collection of articles by many experts in this volume provides a comprehensive overview of the current state of xenotransplantation research. Each study contributes valuable knowledge to the field, addressing various challenges and proposing innovative solutions.</p>
<p>As we move closer to clinical reality with limited cases happening all over the world, it is imperative to continue interdisciplinary collaboration and rigorous research to overcome the remaining hurdles in xenotransplantation worldwide. This collective effort will lead to successful clinical trials and ultimately, a wider application of xenotransplantation in addressing the organ shortage crisis globally.</p>
</sec>
<sec id="s12" sec-type="author-contributions">
<title>Author contributions</title>
<p>LM: Writing &#x2013; original draft. BE: Writing &#x2013; review &amp; editing.</p>
</sec>
</body>
<back>
<sec id="s13" sec-type="funding-information">
<title>Funding</title>
<p>The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Shenzhen Science and Technology Program (JCYJ20230807115107015, GCZX2015043017281705), the National Key R&amp;D Program of China (2017YFC1103704), Shenzhen High-level Hospital Construction Fund (2019).</p>
</sec>
<sec id="s14" sec-type="COI-statement">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec id="s15" sec-type="disclaimer">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
</back>
</article>