Identifying Key Questions and Challenges in Microchimerism Biology

Kristine J Chua¹, Rachel C Quilang², Katja Sallinger³, Christina Athena Aktipis^{4

5}, Petra Arck^{6

7}, Diana W Bianchi^{8

9}, Hyun-Dong Chang^{10

11}, Henderson J Cleaves 2nd¹², Michael Eikmans², Heidi E S Fjeldstad¹³, David Haig¹⁴, Whitney E Harrington^{15

16}, William Horsnell^{17

18}, Daniel P Jacobsen^{13

19}, Mads Kamper-Jørgensen²⁰, Sami B Kanaan²¹, Kiarash Khosrotehrani^{22

23}, Nathalie C Lambert²⁴, Jane Lee Nelson²⁵, Maria B Olsen^{19

26}, Tiffany D Pan²⁷, Jelmer R Prins²⁸, Frank A Schildberg²⁹, Anne Cathrine Staff^{13

19}, Anders Ståhlberg^{30

31}, Ina A Stelzer³², Christopher Urbschat^{6

7}, Sing Sing Way^{33

34}, Melissa A Wilson³⁵, Jody Ye³⁶, Thomas Kroneis³, Amy M Boddy³⁷

Affiliations

¹ Department of Anthropology, University of Notre Dame, Notre Dame, 46556, USA.
² Department of Immunology, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands.
³ Department of Cell Biology, Histology & Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, 8010, Austria.
⁴ Center for Evolution and Medicine, Arizona State University, Tempe, 85287, USA.
⁵ Department of Psychology, Arizona State University, Tempe, 85287, USA.
⁶ Division of Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
⁷ Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
⁸ National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, USA.
⁹ National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, USA.
¹⁰ German Rheumatology Research Center, A Leibniz Institute (DRFZ), 10117, Berlin, Germany.
¹¹ Technische Universität Berlin, Department for Cytometry, Institute of Biotechnology, 13355, Berlin, Germany.
¹² Department of Chemistry, Howard University, Washington, D.C., 20059, USA.
¹³ Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, 0424, Norway.
¹⁴ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, USA.
¹⁵ Department of Pediatrics, University of Washington School of Medicine, Seattle, 98195, USA.
¹⁶ Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, 98105, USA.
¹⁷ MRC Centre for Medical Mycology, University of Exeter, Exeter, EX4 4QJ, UK.
¹⁸ Institute for Infectious Disease and Molecular Medicine, Centre for Infectious Disease Research in Africa and Division of Immunology, University of Cape Town, Cape Town, 7701, South Africa.
¹⁹ Faculty of Medicine, University of Oslo, Oslo, 0316, Norway.
²⁰ Department of Public Health, University of Copenhagen, Copenhagen, DK-1165, Denmark.
²¹ Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, 98109, USA.
²² Frazer institute, The University of Queensland, Woolloongabba, 4072, Australia.
²³ Translational Research institute, The University of Queensland, Woolloongabba, 4072, Australia.
²⁴ INSERM UMRs 1097, ARTHEMIS, Aix Marseille University, Marseille, 13284, France.
²⁵ Medicine, Rheumatology, University of Washington and Fred Hutchinson Cancer Center, Seattle, 98109, USA.
²⁶ Research Institute of Internal Medicine, Oslo University Hospital, Oslo, 0424, Norway.
²⁷ Center for Studies in Demography and Ecology, University of Washington, Seattle, 98195, USA.
²⁸ Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, 9700 AB, The Netherlands.
²⁹ Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127, Bonn, Germany.
³⁰ Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Wallenberg Centre for Molecular and Translational Medicine, Science for Life Laboratory, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 405 30, Sweden.
³¹ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, SE 413 45, Sweden.
³² Pathology, Center for Perinatal Discovery, University of California San Diego, La Jolla, 92037, USA.
³³ Center for Inflammation and Tolerance, Cincinnati Children's Hospital, Cincinnati, 45229, USA.
³⁴ University of Cincinnati College of Medicine, Cincinnati, 45219, USA.
³⁵ National Human Genome Research Institute, National Institutes of Health Bethesda, Bethesda, 20892, USA.
³⁶ Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, 10461, USA.
³⁷ Department of Anthropology, University of California Santa Barbara, Santa Barbara, 93106, USA.

PMID: 41134118
DOI: 10.1002/advs.202514969

Identifying Key Questions and Challenges in Microchimerism Biology

Kristine J Chua et al. Adv Sci (Weinh). 2025.

. 2025 Oct 24:e14969.

doi: 10.1002/advs.202514969. Online ahead of print.

Authors

Affiliations

¹ Department of Anthropology, University of Notre Dame, Notre Dame, 46556, USA.
² Department of Immunology, Leiden University Medical Center, Leiden, 2333 ZA, Netherlands.
³ Department of Cell Biology, Histology & Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, 8010, Austria.
⁴ Center for Evolution and Medicine, Arizona State University, Tempe, 85287, USA.
⁵ Department of Psychology, Arizona State University, Tempe, 85287, USA.
⁶ Division of Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
⁷ Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, 20246, Hamburg, Germany.
⁸ National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, USA.
⁹ National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, 20892, USA.
¹⁰ German Rheumatology Research Center, A Leibniz Institute (DRFZ), 10117, Berlin, Germany.
¹¹ Technische Universität Berlin, Department for Cytometry, Institute of Biotechnology, 13355, Berlin, Germany.
¹² Department of Chemistry, Howard University, Washington, D.C., 20059, USA.
¹³ Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, 0424, Norway.
¹⁴ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, 02138, USA.
¹⁵ Department of Pediatrics, University of Washington School of Medicine, Seattle, 98195, USA.
¹⁶ Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, 98105, USA.
¹⁷ MRC Centre for Medical Mycology, University of Exeter, Exeter, EX4 4QJ, UK.
¹⁸ Institute for Infectious Disease and Molecular Medicine, Centre for Infectious Disease Research in Africa and Division of Immunology, University of Cape Town, Cape Town, 7701, South Africa.
¹⁹ Faculty of Medicine, University of Oslo, Oslo, 0316, Norway.
²⁰ Department of Public Health, University of Copenhagen, Copenhagen, DK-1165, Denmark.
²¹ Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, 98109, USA.
²² Frazer institute, The University of Queensland, Woolloongabba, 4072, Australia.
²³ Translational Research institute, The University of Queensland, Woolloongabba, 4072, Australia.
²⁴ INSERM UMRs 1097, ARTHEMIS, Aix Marseille University, Marseille, 13284, France.
²⁵ Medicine, Rheumatology, University of Washington and Fred Hutchinson Cancer Center, Seattle, 98109, USA.
²⁶ Research Institute of Internal Medicine, Oslo University Hospital, Oslo, 0424, Norway.
²⁷ Center for Studies in Demography and Ecology, University of Washington, Seattle, 98195, USA.
²⁸ Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, 9700 AB, The Netherlands.
²⁹ Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127, Bonn, Germany.
³⁰ Sahlgrenska Center for Cancer Research, Department of Laboratory Medicine, Wallenberg Centre for Molecular and Translational Medicine, Science for Life Laboratory, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 405 30, Sweden.
³¹ Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Region Västra Götaland, Gothenburg, SE 413 45, Sweden.
³² Pathology, Center for Perinatal Discovery, University of California San Diego, La Jolla, 92037, USA.
³³ Center for Inflammation and Tolerance, Cincinnati Children's Hospital, Cincinnati, 45229, USA.
³⁴ University of Cincinnati College of Medicine, Cincinnati, 45219, USA.
³⁵ National Human Genome Research Institute, National Institutes of Health Bethesda, Bethesda, 20892, USA.
³⁶ Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, 10461, USA.
³⁷ Department of Anthropology, University of California Santa Barbara, Santa Barbara, 93106, USA.

PMID: 41134118
DOI: 10.1002/advs.202514969

Abstract

Microchimerism research has recently gained renewed attention despite known existence of these rare cells for decades. Fetal and maternal microchimeric-derived cells may have functional capabilities, and are increasingly associated with both beneficial and adverse health outcomes. Yet, establishing the role of microchimerism in health has been largely constrained methodologically and theoretically. The Microchimerism, Human Health, and Evolution Project address these challenges by calling on 29 leading microchimerism experts to put forth key research questions that can substantially advance the field. Seven major categories are identified: function and mechanism; microchimerism in interventions, treatment, and transplant; mapping "generational microchimerism"; evolution; microchimerism detection; appropriate experimental model systems; and definition of microchimerism. Identifying these questions - and continuing to find answers - will be crucial for advancing the knowledge of microchimerism in health and disease.

Keywords: autoimmunity; detection methods; evolution; immune tolerance; maternal‐fetal interaction; microchimerism; pregnancy.

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References

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Identifying Key Questions and Challenges in Microchimerism Biology

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Identifying Key Questions and Challenges in Microchimerism Biology

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