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Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents

Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we showed in mice that fetal or adult lung progenitors could potentially provide donor cells for transplantation, provided that the lung...

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Autores principales: Milman Krentsis, Irit, Orgad, Ran, Zheng, Yangxi, Bachar Lustig, Esther, Rosen, Chava, Shezen, Elias, Yadav, Sandeep, Nathansohn Levi, Bar, Assayag, Miri, Berkman, Neville, Karmouty Quintana, Harry, Shoshan, Einav, Blagdon, Christa, Reisner, Yair
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929438/
https://www.ncbi.nlm.nih.gov/pubmed/35298657
http://dx.doi.org/10.1093/stcltm/szab016
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author Milman Krentsis, Irit
Orgad, Ran
Zheng, Yangxi
Bachar Lustig, Esther
Rosen, Chava
Shezen, Elias
Yadav, Sandeep
Nathansohn Levi, Bar
Assayag, Miri
Berkman, Neville
Karmouty Quintana, Harry
Shoshan, Einav
Blagdon, Christa
Reisner, Yair
author_facet Milman Krentsis, Irit
Orgad, Ran
Zheng, Yangxi
Bachar Lustig, Esther
Rosen, Chava
Shezen, Elias
Yadav, Sandeep
Nathansohn Levi, Bar
Assayag, Miri
Berkman, Neville
Karmouty Quintana, Harry
Shoshan, Einav
Blagdon, Christa
Reisner, Yair
author_sort Milman Krentsis, Irit
collection PubMed
description Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we showed in mice that fetal or adult lung progenitors could potentially provide donor cells for transplantation, provided that the lung stem cell niche in the recipient is vacated of endogenous lung progenitors by adequate conditioning. Accordingly, marked lung regeneration could be attained following i.v. infusion of a single cell suspension of lung cells into recipient mice conditioned with naphthalene (NA) and 6Gy total body irradiation (TBI). As clinical translation of this approach requires the use of allogenic donors, we more recently developed a novel transplantation modality based on co-infusion of hematopoietic and lung progenitors from the same donor. Thus, by virtue of hematopoietic chimerism, which leads to immune tolerance toward donor antigens, the lung progenitors can be successfully engrafted without any need for post-transplant immune suppression. In the present study, we demonstrate that it is possible to replace NA in the conditioning regimen with Cyclophosphamide (CY), approved for the treatment of many diseases and that a lower dose of 2 GY TBI can successfully enable engraftment of donor-derived hematopoietic and lung progenitors when CY is administered in 2 doses after the stem cell infusion. Taken together, our results suggest a feasible and relatively safe protocol that could potentially be translated to clinical transplantation of lung progenitors across major MHC barriers in patients with terminal lung diseases.
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spelling pubmed-89294382022-03-18 Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents Milman Krentsis, Irit Orgad, Ran Zheng, Yangxi Bachar Lustig, Esther Rosen, Chava Shezen, Elias Yadav, Sandeep Nathansohn Levi, Bar Assayag, Miri Berkman, Neville Karmouty Quintana, Harry Shoshan, Einav Blagdon, Christa Reisner, Yair Stem Cells Transl Med Enabling Technologies for Cell-Based Clinical Translation Over the last decades, several studies demonstrated the possibility of lung regeneration through transplantation of various lung progenitor populations. Recently, we showed in mice that fetal or adult lung progenitors could potentially provide donor cells for transplantation, provided that the lung stem cell niche in the recipient is vacated of endogenous lung progenitors by adequate conditioning. Accordingly, marked lung regeneration could be attained following i.v. infusion of a single cell suspension of lung cells into recipient mice conditioned with naphthalene (NA) and 6Gy total body irradiation (TBI). As clinical translation of this approach requires the use of allogenic donors, we more recently developed a novel transplantation modality based on co-infusion of hematopoietic and lung progenitors from the same donor. Thus, by virtue of hematopoietic chimerism, which leads to immune tolerance toward donor antigens, the lung progenitors can be successfully engrafted without any need for post-transplant immune suppression. In the present study, we demonstrate that it is possible to replace NA in the conditioning regimen with Cyclophosphamide (CY), approved for the treatment of many diseases and that a lower dose of 2 GY TBI can successfully enable engraftment of donor-derived hematopoietic and lung progenitors when CY is administered in 2 doses after the stem cell infusion. Taken together, our results suggest a feasible and relatively safe protocol that could potentially be translated to clinical transplantation of lung progenitors across major MHC barriers in patients with terminal lung diseases. Oxford University Press 2022-02-28 /pmc/articles/PMC8929438/ /pubmed/35298657 http://dx.doi.org/10.1093/stcltm/szab016 Text en © The Author(s) 2022. Published by Oxford University Press. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Enabling Technologies for Cell-Based Clinical Translation
Milman Krentsis, Irit
Orgad, Ran
Zheng, Yangxi
Bachar Lustig, Esther
Rosen, Chava
Shezen, Elias
Yadav, Sandeep
Nathansohn Levi, Bar
Assayag, Miri
Berkman, Neville
Karmouty Quintana, Harry
Shoshan, Einav
Blagdon, Christa
Reisner, Yair
Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title_full Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title_fullStr Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title_full_unstemmed Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title_short Lung Regeneration by Transplantation of Allogeneic Lung Progenitors Using a Safer Conditioning Regimen and Clinical-grade Reagents
title_sort lung regeneration by transplantation of allogeneic lung progenitors using a safer conditioning regimen and clinical-grade reagents
topic Enabling Technologies for Cell-Based Clinical Translation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8929438/
https://www.ncbi.nlm.nih.gov/pubmed/35298657
http://dx.doi.org/10.1093/stcltm/szab016
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