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Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival

Platelet microvesicles (pMVs) are submicron-sized heterogeneous vesicles released upon activation and contain several membrane receptors and proteins (CD41, CD61, CD62, CXCR4, PAR-1, etc.). We have revealed their ability to adhere to the triblock copolymer pluronic-F127 (PF127) and form a platelet m...

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Autores principales: Chander, Vikas, Gangenahalli, Gurudutta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957521/
https://www.ncbi.nlm.nih.gov/pubmed/31932650
http://dx.doi.org/10.1038/s41598-019-57057-8
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author Chander, Vikas
Gangenahalli, Gurudutta
author_facet Chander, Vikas
Gangenahalli, Gurudutta
author_sort Chander, Vikas
collection PubMed
description Platelet microvesicles (pMVs) are submicron-sized heterogeneous vesicles released upon activation and contain several membrane receptors and proteins (CD41, CD61, CD62, CXCR4, PAR-1, etc.). We have revealed their ability to adhere to the triblock copolymer pluronic-F127 (PF127) and form a platelet microvesicular nanocloud which has the potential to enhance the transvascular migration of hematopoietic stem cells across the sinusoidal endothelium to the bone marrow. Besides, the pMVs nanoclouds bestow survival benefits when present on the cells used for infusion, particularly with PF127-stabilized with chitosan-alginate (PF127-CA HSCs). The vesicles were found to be firmly associated with PF127 in the nanocloud, which was detected by confocal laser scanning microscopy. The abrogation of CXCR4/SDF-1 axis regulating the transmigration of the cells by antagonist AMD3100 revealed that the enriched CXCR4 receptors on pMVs robustize the transmigration of the infused cells. The homing of the cells led to effective engraftment and faster regeneration of the critical blood lineages, which elicited 100% survival of the mice receiving lethal doses of radiation. The Human Long-Term Culture Initiating Cells (LTC-ICs), Severe Combined Immunodeficient (SCID) - Repopulating Cells (SRCs) and Colony Forming Cells (CFCs) responsible for the regeneration, but present in extremely low numbers in the infused cell dose, have enabled the cells to reach the bone marrow in high numbers. This potential of the PF127 to sequester the pMVs and its application to achieve over 10-fold delivery of HSCs across the trans-endothelial checkpoint has so far not been reported. Thus, this mechanistic innovation is a potential post-exposure life-saving regimen capable of circumventing the irreparable damage to the bone marrow caused by lethal doses of radiation.
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spelling pubmed-69575212020-01-16 Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival Chander, Vikas Gangenahalli, Gurudutta Sci Rep Article Platelet microvesicles (pMVs) are submicron-sized heterogeneous vesicles released upon activation and contain several membrane receptors and proteins (CD41, CD61, CD62, CXCR4, PAR-1, etc.). We have revealed their ability to adhere to the triblock copolymer pluronic-F127 (PF127) and form a platelet microvesicular nanocloud which has the potential to enhance the transvascular migration of hematopoietic stem cells across the sinusoidal endothelium to the bone marrow. Besides, the pMVs nanoclouds bestow survival benefits when present on the cells used for infusion, particularly with PF127-stabilized with chitosan-alginate (PF127-CA HSCs). The vesicles were found to be firmly associated with PF127 in the nanocloud, which was detected by confocal laser scanning microscopy. The abrogation of CXCR4/SDF-1 axis regulating the transmigration of the cells by antagonist AMD3100 revealed that the enriched CXCR4 receptors on pMVs robustize the transmigration of the infused cells. The homing of the cells led to effective engraftment and faster regeneration of the critical blood lineages, which elicited 100% survival of the mice receiving lethal doses of radiation. The Human Long-Term Culture Initiating Cells (LTC-ICs), Severe Combined Immunodeficient (SCID) - Repopulating Cells (SRCs) and Colony Forming Cells (CFCs) responsible for the regeneration, but present in extremely low numbers in the infused cell dose, have enabled the cells to reach the bone marrow in high numbers. This potential of the PF127 to sequester the pMVs and its application to achieve over 10-fold delivery of HSCs across the trans-endothelial checkpoint has so far not been reported. Thus, this mechanistic innovation is a potential post-exposure life-saving regimen capable of circumventing the irreparable damage to the bone marrow caused by lethal doses of radiation. Nature Publishing Group UK 2020-01-13 /pmc/articles/PMC6957521/ /pubmed/31932650 http://dx.doi.org/10.1038/s41598-019-57057-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chander, Vikas
Gangenahalli, Gurudutta
Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title_full Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title_fullStr Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title_full_unstemmed Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title_short Pluronic-F127/Platelet Microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
title_sort pluronic-f127/platelet microvesicles nanocomplex delivers stem cells in high doses to the bone marrow and confers post-irradiation survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957521/
https://www.ncbi.nlm.nih.gov/pubmed/31932650
http://dx.doi.org/10.1038/s41598-019-57057-8
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