Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model

Zonghu Han; Joseph Sushil Rao; Lakshya Gangwar; Bat Erdene Namsrai; Jacqueline L. Pasek-Allen; Michael L. Etheridge; Susan M. Wolf; Timothy L. Pruett; John C. Bischof; Erik B. Finger

doi:10.1038/s41467-023-38824-8

Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model

Zonghu Han, Joseph Sushil Rao, Lakshya Gangwar, Bat Erdene Namsrai, Jacqueline L. Pasek-Allen, Michael L. Etheridge, Susan M. Wolf, Timothy L. Pruett, John C. Bischof, Erik B. Finger

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Abstract

Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.

Original language	English (US)
Article number	3407
Journal	Nature communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-38824-8
State	Published - Dec 2023

Bibliographical note

Funding Information:
Z.H. and J.S.R contributed equally as co-first authors and are listed in alphabetical order. J.C.B. and E.B.F. contributed equally as co-senior and corresponding authors. We acknowledge Dr. Usha Kini (St. John’s National Academy of Health Sciences, India) for interpreting histologic samples; Diane Tobolt, Mikaela Hintz, and Saurin Kantesaria for technical assistance; Andy Grams for technical illustration; Dr. Michael Lotti for editorial assistance; and Dr. Greg Fahy for scientific discussion on CPA formulation. Some figures were created with BioRender.com (Figs. , , and ). This work was supported by NIH grants DK117425 (E.B.F, J.C.B.), HL135046 (E.B.F, J.C.B.), DK131209 (E.B.F, J.C.B.), and DK132211 (E.B.F, J.C.B.), NSF grant EEC-1941543 (E.B.F, J.C.B., T.L.P., S.M.W.), and a gift from the Biostasis Research Institute funded in part through contributions from LifeGift, Nevada Donor Network, Lifesource, Donor Network West, and Lifebanc.

Funding Information:
Z.H. and J.S.R contributed equally as co-first authors and are listed in alphabetical order. J.C.B. and E.B.F. contributed equally as co-senior and corresponding authors. We acknowledge Dr. Usha Kini (St. John’s National Academy of Health Sciences, India) for interpreting histologic samples; Diane Tobolt, Mikaela Hintz, and Saurin Kantesaria for technical assistance; Andy Grams for technical illustration; Dr. Michael Lotti for editorial assistance; and Dr. Greg Fahy for scientific discussion on CPA formulation. Some figures were created with BioRender.com (Figs. 1 , 4 , and 7). This work was supported by NIH grants DK117425 (E.B.F, J.C.B.), HL135046 (E.B.F, J.C.B.), DK131209 (E.B.F, J.C.B.), and DK132211 (E.B.F, J.C.B.), NSF grant EEC-1941543 (E.B.F, J.C.B., T.L.P., S.M.W.), and a gift from the Biostasis Research Institute funded in part through contributions from LifeGift, Nevada Donor Network, Lifesource, Donor Network West, and Lifebanc.

Publisher Copyright:
© 2023, The Author(s).

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

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Han, Z., Rao, J. S., Gangwar, L., Namsrai, B. E., Pasek-Allen, J. L., Etheridge, M. L., Wolf, S. M., Pruett, T. L., Bischof, J. C., & Finger, E. B. (2023). Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model. Nature communications, 14(1), Article 3407. https://doi.org/10.1038/s41467-023-38824-8

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title = "Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model",

abstract = "Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.",

author = "Zonghu Han and Rao, {Joseph Sushil} and Lakshya Gangwar and Namsrai, {Bat Erdene} and Pasek-Allen, {Jacqueline L.} and Etheridge, {Michael L.} and Wolf, {Susan M.} and Pruett, {Timothy L.} and Bischof, {John C.} and Finger, {Erik B.}",

note = "Funding Information: Z.H. and J.S.R contributed equally as co-first authors and are listed in alphabetical order. J.C.B. and E.B.F. contributed equally as co-senior and corresponding authors. We acknowledge Dr. Usha Kini (St. John{\textquoteright}s National Academy of Health Sciences, India) for interpreting histologic samples; Diane Tobolt, Mikaela Hintz, and Saurin Kantesaria for technical assistance; Andy Grams for technical illustration; Dr. Michael Lotti for editorial assistance; and Dr. Greg Fahy for scientific discussion on CPA formulation. Some figures were created with BioRender.com (Figs. , , and ). This work was supported by NIH grants DK117425 (E.B.F, J.C.B.), HL135046 (E.B.F, J.C.B.), DK131209 (E.B.F, J.C.B.), and DK132211 (E.B.F, J.C.B.), NSF grant EEC-1941543 (E.B.F, J.C.B., T.L.P., S.M.W.), and a gift from the Biostasis Research Institute funded in part through contributions from LifeGift, Nevada Donor Network, Lifesource, Donor Network West, and Lifebanc. Funding Information: Z.H. and J.S.R contributed equally as co-first authors and are listed in alphabetical order. J.C.B. and E.B.F. contributed equally as co-senior and corresponding authors. We acknowledge Dr. Usha Kini (St. John{\textquoteright}s National Academy of Health Sciences, India) for interpreting histologic samples; Diane Tobolt, Mikaela Hintz, and Saurin Kantesaria for technical assistance; Andy Grams for technical illustration; Dr. Michael Lotti for editorial assistance; and Dr. Greg Fahy for scientific discussion on CPA formulation. Some figures were created with BioRender.com (Figs. 1 , 4 , and 7). This work was supported by NIH grants DK117425 (E.B.F, J.C.B.), HL135046 (E.B.F, J.C.B.), DK131209 (E.B.F, J.C.B.), and DK132211 (E.B.F, J.C.B.), NSF grant EEC-1941543 (E.B.F, J.C.B., T.L.P., S.M.W.), and a gift from the Biostasis Research Institute funded in part through contributions from LifeGift, Nevada Donor Network, Lifesource, Donor Network West, and Lifebanc. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

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AU - Namsrai, Bat Erdene

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AU - Etheridge, Michael L.

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AU - Pruett, Timothy L.

AU - Bischof, John C.

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N2 - Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.

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Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model

Abstract

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