{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:09Z","timestamp":1792789089974,"version":"4.5.0"},"reference-count":35,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32673665"],"award-info":[{"award-number":["32673665"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32673665"],"award-info":[{"award-number":["32673665"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["TD2024C002"],"award-info":[{"award-number":["TD2024C002"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Innovation Project of Heilongjiang Academy of Agriculture Sciences","award":["CX23ZD06"],"award-info":[{"award-number":["CX23ZD06"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-34"],"award-info":[{"award-number":["CARS-34"]}],"id":[{"id":"https:\/\/ror.org\/03p5eky76","id-type":"ROR","asserted-by":"crossref"}]},{"award":["CARS-34"],"award-info":[{"award-number":["CARS-34"]}],"id":[{"id":"https:\/\/ror.org\/03p5eky76","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breakthroughs in gene-editing technologies have brought pig-to-human xenotransplantation to the clinical forefront. Nevertheless, the micro-scale impacts of the complex pathophysiological milieu within recipients on grafts have long been overlooked by the academic community. Focusing on stromal vascular fraction (SVF) cells and preadipocytes widely present in donor organs, this study explores the potential mechanism underlying beige adipogenesis induced by post-operative anti-inflammatory drugs (e.g., dexamethasone) and surgical stress (norepinephrine), as well as its possible relationship with host immune system activation. The literature search and study-selection reporting were informed by PRISMA 2020. Five information sources were searched, and nine relevant studies on experimentally induced porcine adipose beiging, predominantly in vitro, were included in marker-specific meta-analyses. The meta-analysis showed a higher pooled expression of CD137, CIDEA, UCP3, PGC1\u03b1 and DIO2 during experimentally induced porcine beige adipogenesis. To explore the structural plausibility of cross-species interaction, molecular docking analysis of the candidate protein CD137 was performed using AlphaFold 3. The predicted binding energies were \u22129.4 kcal\/mol for porcine CD137\u2013human CD137L and \u22129.0 kcal\/mol for the human homologous complex. These computational predictions suggest a structurally plausible interaction, but the results do not demonstrate stronger biological binding, macrophage activation, or immune rejection. Overall, the findings support a hypothesis that porcine adipocyte beiging and CD137-related cross-species interactions may be relevant to xenograft immunometabolism; direct experimental validation in xenotransplantation models is required.<\/jats:p>","DOI":"10.3390\/cells15191758","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:18:46Z","timestamp":1790583526000},"page":"1758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Meta-Analysis of Porcine Beige Adipogenesis with Cross-Species CD137-CD137L Molecular Docking: Potential Implications for Pig-to-Human Xenotransplantation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0592-5988","authenticated-orcid":false,"given":"Zhenhua","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmiao","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ma","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Key Laboratory of Combining Farming and Animal Husbandry, Ministry of Agriculture and Rural Affairs, No. 368 Xuefu Road, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70137","DOI":"10.1111\/xen.70137","article-title":"Early Experimental Report of the First 8-Gene-Edited Pig-to-Rhesus Macaque Cardiac Xenotransplantation in China","volume":"33","author":"Wang","year":"2026","journal-title":"Xenotransplantation"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Liu, H., Hoang, T., Hu, Y., Xu, Y., Sun, Z., Peiffer, B.J., Huang, Y., Sun, Z., and Zhang, H. (2026). Proteomic Identification of Pig Xenoantigens for Clinical Xenotransplantation. bioRxiv.","DOI":"10.64898\/2026.05.22.727249"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101148","DOI":"10.1016\/j.medj.2026.101148","article-title":"First human decedent model of orthotopic multi-organ xenotransplantation: Whole liver and bilateral kidneys from a six-gene-edited pig","volume":"7","author":"Liao","year":"2026","journal-title":"Med"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1016\/j.healun.2024.07.022","article-title":"Extended survival of 9- and 10-gene-edited pig heart xenografts with ischemia minimization and CD154 costimulation blockade-based immunosuppression","volume":"43","author":"Chaban","year":"2024","journal-title":"J. Heart Lung Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/SLA.0000000000006380","article-title":"Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation","volume":"280","author":"Anderson","year":"2024","journal-title":"Ann. Surg."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Kim, S., Yazawa, T., Koide, A., Yoneda, E., Aoki, R., Okazaki, T., Tomita, K., Watanabe, H., Muroi, Y., and Testuka, M. (2024). Potential Role of Pig UCP3 in Modulating Adipocyte Browning via the Beta-Adrenergic Receptor Signaling Pathway. Biology, 13.","DOI":"10.3390\/biology13050284"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/d41586-024-01453-2","article-title":"Pig-organ transplants: What three human recipients have taught scientists","volume":"629","author":"Kozlov","year":"2024","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.hbpd.2026.04.009","article-title":"Liver xenotransplantation: Progress, mechanistic barriers and strategies for clinical translation","volume":"25","author":"Mang","year":"2026","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Henderson, D., Knoedler, L., Mathieu, O., Rouas-Freiss, N., Cetrulo, C.L., Lemaitre, G., Smadja, D.M., Fortunel, N.O., and Lellouch, A.G. (2026). Porcine xenotransplantation in the clinical era: Converging advances and unresolved barriers on the path to clinical translation\u2014A narrative review. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1866007"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s12265-026-10800-9","article-title":"Immunometabolic Remodeling in Ischemic and Non-Ischemic Heart Failure","volume":"19","author":"Zang","year":"2026","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/17460751.2026.2663179","article-title":"Multilineage-differentiating stress-enduring (Muse) cells in ischemic heart disease. A systematic review of preclinical and clinical studies","volume":"21","author":"Seelan","year":"2026","journal-title":"Regen. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.ijbiomac.2022.11.231","article-title":"A Ganoderma lucidum polysaccharide F31 alleviates hyperglycemia through kidney protection and adipocyte apoptosis","volume":"226","author":"Jiao","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s13287-025-04225-5","article-title":"Adipose stromal cells increase insulin sensitivity and decrease liver gluconeogenesis in a mouse model of type 1 diabetes mellitus","volume":"16","author":"Lai","year":"2025","journal-title":"Stem Cell Res. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1579062","DOI":"10.3389\/fbioe.2025.1579062","article-title":"An engineered adipose formulation decreases hepatic inflammation and fibrosis in a rodent model of metabolic dysfunction-associated steatotic liver disease","volume":"13","author":"Choi","year":"2025","journal-title":"Front. Bioeng. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103906","DOI":"10.1016\/j.jtherbio.2024.103906","article-title":"Differential expression of ADRB1 causes different responses to norepinephrine in adipocytes of Duroc-Landrace-Yorkshire pigs and min pigs","volume":"123","author":"Zhao","year":"2024","journal-title":"J. Therm. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"106679","DOI":"10.1016\/j.domaniend.2021.106679","article-title":"Skeletal muscle-secreted myokine interleukin-6 induces white adipose tissue conversion into beige adipose tissue in myostatin gene knockout pigs","volume":"78","author":"Xuan","year":"2022","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bbrc.2022.06.047","article-title":"Nonivamide induces brown fat-like characteristics in porcine subcutaneous adipocytes","volume":"619","author":"Zhao","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, H., Wu, J., Fang, Y., and Li, Q. (2025). MD Simulation Reveals a Trimerization-Enhanced Interaction of CD137L with CD137. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26051903"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Liu, Y., Yang, Z., Xiang, Y., Cheng, G., Chen, L., Wang, S., Zang, M., Zhou, N., Zhang, X., and Chen, R. (2025). Single-cell analysis reveals an important role of CD137L+ macrophages in the host response to uropathogenic Escherichia coli infection in the bladder. PLoS Pathog., 21.","DOI":"10.1371\/journal.ppat.1013543"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liu, J., Jiang, Y., Chen, C., Zhang, L., Wang, J., Yang, C., Wu, T., Yang, S., Tao, C., and Wang, Y. (2024). Bone Morphogenetic Protein 2 Enhances Porcine Beige Adipogenesis via AKT\/mTOR and MAPK Signaling Pathways. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25073915"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/lipd.12010","article-title":"Divergent Response of Murine and Porcine Adipocytes to Stimulation of Browning Genes by 18-Carbon Polyunsaturated Fatty Acids and Beta-Receptor Agonists","volume":"53","author":"Shin","year":"2018","journal-title":"Lipids"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zhang, L., Hu, S., Cao, C., Chen, C., Liu, J., Wang, Y., Liu, J., Zhao, J., Tao, C., and Wang, Y. (2022). Functional and Genetic Characterization of Porcine Beige Adipocytes. Cells, 11.","DOI":"10.3390\/cells11040751"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3103\/S0095452724010080","article-title":"TAP2 Effect on Min-Pig Stromal Vascular Fraction Cell Gene Expression","volume":"58","author":"Wang","year":"2024","journal-title":"Cytol. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yang, S., Ma, H., Wang, L., Wang, F., Xia, J., Liu, D., Mu, L., Yang, X., and Liu, D. (2024). The Role of beta3-Adrenergic Receptors in Cold-Induced Beige Adipocyte Production in Pigs. Cells, 13.","DOI":"10.3390\/cells13080709"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e621","DOI":"10.1016\/S2352-3026(25)00162-0","article-title":"Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): A randomised, open-label, multicentre, phase 3 trial","volume":"12","author":"Bringhen","year":"2025","journal-title":"Lancet Haematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40780-023-00310-0","article-title":"Induction of CYP3A activity by dexamethasone may not be strong, even at high doses: Insights from a case of tacrolimus co-administration","volume":"9","author":"Ohno","year":"2023","journal-title":"J. Pharm. Health Care Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.12659\/AOT.883960","article-title":"Norepinephrine versus dopamine pretreatment of potential heart donors\u2014Impact on long-term outcome","volume":"18","author":"Helbig","year":"2013","journal-title":"Ann. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.transproceed.2024.11.037","article-title":"Factors Impacting Early Adverse Outcomes in Simultaneous Heart-Kidney Transplantation","volume":"57","author":"DuBray","year":"2025","journal-title":"Transplant. Proc."},{"key":"ref_29","first-page":"e80553","article-title":"Prolonged Amphetamine-Dextroamphetamine Use: An Unrecognized Cause of Cardiomyopathy","volume":"17","author":"Habeb","year":"2025","journal-title":"Cureus"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liu, J., Jiang, Y., Liu, T., Chen, C., Chui, L., Cui, A., Zhang, X., Wang, X., Wang, Y., and Yang, C. (2025). Single-nucleus RNA sequencing defines adipose tissue subpopulations that contribute to Tibetan pig cold adaptation. BMC Biol., 23.","DOI":"10.1186\/s12915-025-02211-0"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/PRS.0000000000011743","article-title":"Brown Adipose Tissue Improves Angiogenesis and M2 Macrophage Polarization in Burn Wounds by Activating Interleukin-17 Signaling","volume":"155","author":"Zhou","year":"2025","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eadn5229","DOI":"10.1126\/sciadv.adn5229","article-title":"Macrophage-derived chemokine CCL22 establishes local LN-mediated adaptive thermogenesis and energy expenditure","volume":"10","author":"Yuan","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s00266-023-03782-5","article-title":"A Study on the Acquisition and Identification of Beige Adipocytes and Exosomes as Well as Their Inflammatory Regulation by Promoting Macrophage Polarization","volume":"48","author":"Wu","year":"2024","journal-title":"Aesthet. Plast. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/bbb\/zbae033","article-title":"A modified system using macrophage-conditioned medium revealed that the indirect effects of anti-inflammatory food-derived compounds improve inflammation-induced suppression of UCP-1 mRNA expression in 10T1\/2 adipocytes","volume":"88","author":"Takahashi","year":"2024","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_35","unstructured":"Gallerand, A., Caillot, Z., Terekhova, M., Castiglione, A., Leporati, L., Giacchero, M., Pilot, T., Chang, M., Dolfi, B., and Zair, F.N. (2024). CD226 (+) adipose tissue macrophages arise from MDP-derived monocytes and regulate lipid metabolism. bioRxiv."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1758\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:13:42Z","timestamp":1790741622000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":35,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cells15191758"],"URL":"https:\/\/doi.org\/10.3390\/cells15191758","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]}}}