Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Therapeutic implications of transplanted-cell death

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

Subjects

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

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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

References

  1. Martin, I., Galipeau, J., Kessler, C., Blanc, K. L. & Dazzi, F. Sci. Transl. Med. 11, eaat2189 (2019).

    Article  CAS  PubMed  Google Scholar 

  2. Galipeau, J. & Sensébé, L. Cell Stem Cell 22, 824–833 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Bianco, P. et al. Nat. Med. 19, 35–42 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fibbe, W. E., Dazzi, F. & LeBlanc, K. Nat. Med. 19, 812–813 (2013).

    Article  CAS  PubMed  Google Scholar 

  5. Cyranoski, D. Nature 565, 544–545 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Panés, J. et al. Lancet 388, 1281–1290 (2016).

    Article  PubMed  Google Scholar 

  7. Sipp, D., Robey, P. G. & Turner, L. Nature 561, 455–457 (2018).

    Article  CAS  PubMed  Google Scholar 

  8. Caplan, A. I. Nature 566, 39 (2019).

    Article  CAS  PubMed  Google Scholar 

  9. Galipeau, J., Weiss, D. J. & Dominici, M. Cytotherapy 21, 1–2 (2019).

    Article  PubMed  Google Scholar 

  10. Caplan, A. I. J. Orthop. Res. 9, 641–650 (1991).

    Article  CAS  PubMed  Google Scholar 

  11. Caplan, A. I. Stem Cells Transl. Med. 6, 1445–1451 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Singer, N. G. & Caplan, A. I. Annu. Rev. Pathol. 6, 457–478 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Uccelli, A., Moretta, L. & Pistoia, V. Nat. Rev. Immunol. 8, 726–736 (2008).

    Article  CAS  PubMed  Google Scholar 

  14. Leibacher, J. & Henschler, R. Stem Cell Res. Ther. 7, 7 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Parekkadan, B. & Milwid, J. M. Annu. Rev. Biomed. Eng. 12, 87–117 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ankrum, J. & Karp, J. M. Trends Mol. Med. 16, 203–209 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Salvadori, M. et al. Mol. Ther. Methods Clin. Dev. 14, 1–15 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moll, G. et al. Adv. Exp. Med. Biol. 951, 77–98 (2016).

    Article  CAS  PubMed  Google Scholar 

  19. Fischer, U. M. et al. Stem Cells Dev. 18, 683–691 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Eggenhofer, E. et al. Front. Immunol. 3, 297 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. von Bahr, L. et al. Stem Cells 30, 1575–1578 (2012).

    Article  Google Scholar 

  22. Liu, L. et al. EBioMedicine 47, 563–577 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Ghahremani Piraghaj, M. et al. Life Sci. 212, 203–212 (2018).

    Article  CAS  PubMed  Google Scholar 

  24. Eggenhofer, E., Luk, F., Dahlke, M. H. & Hoogduijn, M. J. Front. Immunol. 5, 148 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Braza, F. et al. Stem Cells 34, 1836–1845 (2016).

    Article  CAS  PubMed  Google Scholar 

  26. Mathias, L. J. et al. J. Immunol. 191, 5914–5924 (2013).

    Article  CAS  PubMed  Google Scholar 

  27. Jiang, Y. et al. Basic Res. Cardiol. 105, 431–442 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Lu, W. et al. Int. J. Cardiol. 165, 333–340 (2013).

    Article  PubMed  Google Scholar 

  29. Ben-Mordechai, T. et al. J. Am. Coll. Cardiol. 62, 1890–1901 (2013).

    Article  PubMed  Google Scholar 

  30. Thum, T., Bauersachs, J., Poole-Wilson, P. A., Volk, H.-D. & Anker, S. D. J. Am. Coll. Cardiol. 46, 1799–1802 (2005).

    Article  CAS  PubMed  Google Scholar 

  31. Carty, F., Mahon, B. P. & English, K. Clin. Exp. Immunol. 188, 1–11 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. de Witte, S. F. H. et al. Stem Cells 36, 602–615 (2018).

    Article  PubMed  Google Scholar 

  33. Luk, F. et al. Stem Cells Dev. 25, 1342–1354 (2016).

    Article  CAS  PubMed  Google Scholar 

  34. Galleu, A. et al. Sci. Transl. Med. 9, eaam7828 (2017).

    Article  PubMed  Google Scholar 

  35. Abdolmaleki, F. et al. Front. Immunol. 9, 1645 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Nagata, S., Hanayama, R. & Kawane, K. Cell 140, 619–630 (2010).

    Article  CAS  PubMed  Google Scholar 

  37. Boada-Romero, E., Martinez, J., Heckmann, B. L. & Green, D. R. Nat. Rev. Mol. Cell Biol. 21, 398–414 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Poon, I. K. H., Lucas, C. D., Rossi, A. G. & Ravichandran, K. S. Nat. Rev. Immunol. 14, 166–180 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Weiss, D. J. et al. Front. Immunol. 10, 1191 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jackson, M. V. et al. Stem Cells 34, 2210–2223 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Fleshner, M. & Crane, C. R. Trends Immunol. 38, 768–776 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Németh, K. et al. Nat. Med. 15, 42–49 (2009).

    Article  PubMed  Google Scholar 

  43. Jäger, R. & Fearnhead, H. O. Biochem. Res. Int. 2012, e453838 (2012).

    Article  Google Scholar 

  44. Cheung, T. S., Galleu, A., von Bonin, M., Bornhäuser, M. & Dazzi, F. Haematologica 104, e438–e441 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Riazifar, M. et al. ACS Nano 13, 6670–6688 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gonçalves, Fd. C. et al. Sci. Rep. 7, 12100 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Phinney, D. G. et al. Nat. Commun. 6, 8472 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lalu, M. M. et al. PLoS ONE 7, e47559 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Moll, G. et al. Stem Cells 30, 1565–1574 (2012).

    Article  CAS  PubMed  Google Scholar 

  50. Moll, G. et al. Trends Mol. Med. 25, 149–163 (2019).

    Article  PubMed  Google Scholar 

  51. Moll, G. & Blanc, K. L. ISBT Sci. Ser. 10, 357–365 (2015).

    Article  Google Scholar 

  52. Hicks, A. U., MacLellan, C. L., Chernenko, G. A. & Corbett, D. Brain Res. 1231, 103–112 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Liao, L.-Y., Lau, B. W.-M., Sánchez-Vidaña, D. I. & Gao, Q. Neural Regen. Res. 14, 1129–1137 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Donegà, M., Giusto, E., Cossetti, C. & Pluchino, S. in Neural Stem Cells: New Perspectives https://doi.org/10.5772/55426 (IntechOpen, 2013).

  55. Vannella, K. M. & Wynn, T. A. Annu. Rev. Physiol. 79, 593–617 (2017).

    Article  CAS  PubMed  Google Scholar 

  56. Wynn, T. A. & Vannella, K. M. Immunity 44, 450–462 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Mosser, D. M. & Edwards, J. P. Nat. Rev. Immunol. 8, 958–969 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Korns, D. R. P., Frasch, S. C. P., Fernandez-Boyanapalli, R. P., Henson, P. M. P. & Bratton, D. L. M. Front. Immunol. 2, 57 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Spiller, K. L. & Koh, T. J. Adv. Drug Deliv. Rev. 122, 74–83 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yin, J. Q., Zhu, J. & Ankrum, J. A. Nat. Biomed. Eng. 3, 90–104 (2019).

    Article  CAS  PubMed  Google Scholar 

  61. Stabler, C. L., Li, Y., Stewart, J. M. & Keselowsky, B. G. Nat. Rev. Mater. 4, 429–450 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Tuettenberg, A., Steinbrink, K. & Schuppan, D. Nanomedicine 11, 2735–2751 (2016).

    Article  CAS  PubMed  Google Scholar 

  63. Smith, T. D., Nagalla, R. R., Chen, E. Y. & Liu, W. F. Adv. Drug Deliv. Rev. 114, 193–205 (2017).

    Article  CAS  PubMed  Google Scholar 

  64. Ankrum, J. A., Dastidar, R. G., Ong, J. F., Levy, O. & Karp, J. M. Sci. Rep. 4, 4645 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Zhang, F. et al. Nat. Commun. 10, 3974 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Phinney, D. G. & Pittenger, M. F. Stem Cells 35, 851–858 (2017).

    Article  CAS  PubMed  Google Scholar 

  67. Théry, C., Ostrowski, M. & Segura, E. Nat. Rev. Immunol. 9, 581–593 (2009).

    Article  PubMed  Google Scholar 

  68. Riazifar, M., Pone, E. J., Lötvall, J. & Zhao, W. Annu. Rev. Pharmacol. Toxicol. 57, 125–154 (2017).

    Article  CAS  PubMed  Google Scholar 

  69. Armstrong, J. P. K., Holme, M. N. & Stevens, M. M. ACS Nano 11, 69–83 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Harel-Adar, T. et al. Proc. Natl Acad. Sci. USA 108, 1827–1832 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Bagalkot, V., Deiuliis, J. A., Rajagopalan, S. & Maiseyeu, A. Adv. Drug Deliv. Rev. 99, 2–11 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Saas, P., Daguindau, E. & Perruche, S. Stem Cells 34, 1464–1473 (2016).

    Article  PubMed  Google Scholar 

  73. Pilon, C. et al. Front. Immunol. 10, 2908 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhang, B. et al. Cytotherapy 20, 687–696 (2018).

    Article  CAS  PubMed  Google Scholar 

  75. Shigemoto-Kuroda, T. et al. Stem Cell Rep. 8, 1214–1225 (2017).

    Article  CAS  Google Scholar 

  76. Lankford, K. L. et al. PLoS ONE 13, e0190358 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Henao Agudelo, J. S. et al. Front. Immunol. 8, 881 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Song, Y. et al. Stem Cells 35, 1208–1221 (2017).

    Article  CAS  PubMed  Google Scholar 

  79. Domenis, R. et al. Sci. Rep. 8, 13325 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Patel, A. N. et al. Lancet 387, 2412–2421 (2016).

    Article  CAS  PubMed  Google Scholar 

  81. Giri, J. & Galipeau, J. Blood Adv. 4, 1987–1997 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Giri, J., Das, R., Nylen, E., Chinnadurai, R. & Galipeau, J. Cell Rep. 30, 1923–1934.e4 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Shi, Y. et al. Nat. Rev. Nephrol. 14, 493–507 (2018).

    Article  CAS  PubMed  Google Scholar 

  84. Matthay, M. A. et al. Lancet Respir. Med. 7, 154–162 (2019).

    Article  PubMed  Google Scholar 

  85. Caplan, H. et al. Front. Immunol. 10, 1645 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kallmeyer, K. et al. Stem Cells Transl. Med. 9, 131–144 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Braid, L. R., Wood, C. A., Wiese, D. M. & Ford, B. N. Cytotherapy 20, 232–244 (2018).

    Article  PubMed  Google Scholar 

  88. Le Blanc, K. et al. Lancet 363, 1439–1441 (2004).

    Article  PubMed  Google Scholar 

  89. Segaliny, A. I. et al. EBioMedicine 45, 39–57 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Liao, W. et al. Biomaterials 77, 87–97 (2016).

    Article  CAS  PubMed  Google Scholar 

  91. Gupta, N. et al. J. Immunol. 179, 1855–1863 (2007).

    Article  CAS  PubMed  Google Scholar 

  92. Kavanagh, H. & Mahon, B. P. Allergy 66, 523–531 (2011).

    Article  CAS  PubMed  Google Scholar 

  93. Sun, J. et al. Cell. Physiol. Biochem. 27, 587–596 (2011).

    Article  CAS  PubMed  Google Scholar 

  94. Chang, C.-L. et al. J. Transl. Med. 10, 244 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

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

Authors
  1. Zachary W. Wagoner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weian Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weian Zhao.

Ethics declarations

Competing interests

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41551-021-00729-6

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research