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Cryo-imaging of Stem Cell Biodistribution in Mouse Model of Graft-Versus-Host-Disease

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Abstract

We demonstrated the use of multispectral cryo-imaging and software to analyze human mesenchymal stromal cells (hMSCs) biodistribution in mouse models of graft-versus-host-disease (GVHD) following allogeneic bone marrow transplantation (BMT). We injected quantum dot labeled MSCs via tail vein to mice receiving BMT and analyzed hMSC biodistribution in major organs (e.g. lung, liver, spleen, kidneys and bone marrow). We compared the biodistribution of hMSCs in mice following allogeneic BMT recipients (with GVHD) to the biodistribution following syngeneic BMT (without GVHD). Cryo-imaging system revealed cellular biodistribution and redistribution patterns in the animal model. We initially found clusters of cells in the lung that eventually dissociated to single cells and redistributed to other organs within 72 h. The in vivo half-life of the exogenous MSCs was about 21 h. We found that the biodistribution of stromal cells was not related to blood flow, rather cells preferentially homed to specific organs. In conclusion, cryo-imaging was suitable for analyzing the cellular biodistribution. It could provide capabilities of visualizing cells anywhere in the mouse model with single cell sensitivity. By characterizing the biodistribution and anatomical specificity of a therapeutic cellular product, we believe that cryo-imaging can play an important role in the advancement of stem and stromal cell therapies and regenerative medicine.

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Acknowledgments

The research was supported by an Ohio Third Frontier Wright Projects Program award (OTFWPP) (D.L.W., co-I), National Center of Regenerative Medicine Pilot Grant (K.R.C.), the Ohio Board of Regents (K.R.C.), the Meredith Cowden Foundation (K.R.C.), The Thailand Research Fund MRG6080218 (P.W.), and the National Institute of Health through R42-CA124270, R41HD063241-01 (D.L.W.).

Conflict of interest

Dr. Gargesha (M.G.) declares that he is an employee of BioInVision Inc. which is a company that manufactures CryoViz™, a system that utilizes the cryo-imaging principle as the core technology. The rest of the authors (P.W., S.E., K.R.C., D.L.W.) declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Computer Engineering, Faculty of Engineering, Chiang Mai University, Chiang Mai, 50200, Thailand

    Patiwet Wuttisarnwattana

  2. Biomedical Engineering Institute, Chiang Mai University, Chiang Mai, Thailand

    Patiwet Wuttisarnwattana

  3. Department of Pediatric Hematology and Oncology, Case Western Reserve University, Cleveland, OH, USA

    Saada Eid

  4. BioInVision, Inc., Mayfield Village, OH, USA

    Madhusudhana Gargesha

  5. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD, USA

    Kenneth R. Cooke

  6. Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA

    David L. Wilson

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  1. Patiwet Wuttisarnwattana
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  2. Saada Eid
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  3. Madhusudhana Gargesha
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  4. Kenneth R. Cooke
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  5. David L. Wilson
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Correspondence to Patiwet Wuttisarnwattana.

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Associate Editor Smadar Cohen oversaw the review of this article.

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Wuttisarnwattana, P., Eid, S., Gargesha, M. et al. Cryo-imaging of Stem Cell Biodistribution in Mouse Model of Graft-Versus-Host-Disease. Ann Biomed Eng 48, 1702–1711 (2020). https://doi.org/10.1007/s10439-020-02487-z

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