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Therapeutic implications of transplanted-cell death

Nature Biomedical Engineering volume 5, pages 379–384 (2021)Cite this article

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The phagocytic clearance of the large fraction of transplanted cells that typically undergo rapid cell death contributes to therapeutic outcomes.

Cell therapies have produced mixed clinical outcomes. Haematopoietic stem cells, chimeric antigen receptor T cells and other cell products with a well-defined mechanism of action (MOA) tend to perform well; but those cell products with poorly defined MOAs have had limited success. In particular, mesenchymal stromal cells (MSCs) have been a subject of intense focus over the past two decades, with over 700 clinical trials reported across a range of diseases. Overall, MSCs have a positive safety profile, yet the majority of efficacy studies of MSC transplantation therapies have failed to deliver1,2,3,4. Even for the few MSC products that have been clinically approved (for treating graft-versus-host disease (GvHD), complex perianal fistulas and spinal-cord injury, in particular), their overall clinical efficacy and adoption remain unclear2,5,6. Also, their unapproved use in clandestine stem cell clinics has led to hype and to provocative debate within scientific communities and the public regarding whether these therapies work and whether they should be excluded from scientific forums, peer-reviewed journals and research funding7,8,9.

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Fig. 1: Potential mechanisms of cell therapy.
Fig. 2: Therapeutic targeting of phagocytosis and of cell-clearance pathways.

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Acknowledgements

We thank J. Gu for helpful comments. This work was supported by the NIH grants 1DP2CA195763, R21CA219225 and P2CHD086843 (the Alliance for Regenerative Rehabilitation Research & Training; AR3T), and by DOD/CDMRP W81XWH-17-1-0522 and NSF/SBIR no. 1913404.

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Authors and Affiliations

  1. Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA

    Zachary W. Wagoner & Weian Zhao

  2. Department of Pharmaceutical Sciences, University of California, Irvine, Irvine, CA, USA

    Zachary W. Wagoner & Weian Zhao

  3. Chao Family Comprehensive Cancer Center, University of California, Irvine, Irvine, CA, USA

    Weian Zhao

  4. Edwards Life Sciences Center for Advanced Cardiovascular Technology, University of California, Irvine, Irvine, CA, USA

    Weian Zhao

  5. Department of Biomedical Engineering, University of California, Irvine, Irvine, CA, USA

    Weian Zhao

  6. Department of Biological Chemistry, University of California, Irvine, Irvine, CA, USA

    Weian Zhao

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  1. Zachary W. Wagoner
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Correspondence to Weian Zhao.

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Competing interests

W.Z. is a co-founder of Velox Biosystems Inc., Amberstone Biosciences Inc. and Arvetas Biosciences Inc.

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Wagoner, Z.W., Zhao, W. Therapeutic implications of transplanted-cell death. Nat Biomed Eng 5, 379–384 (2021). https://doi.org/10.1038/s41551-021-00729-6

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