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Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
BACKGROUND: Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking s...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405448/ https://www.ncbi.nlm.nih.gov/pubmed/32758261 http://dx.doi.org/10.1186/s12967-020-02470-1 |
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author | Woods, Erik J. Sherry, Aubrey M. Woods, John R. Hardin, James W. LaFontaine, Michael Brandacher, Gerald Johnstone, Brian H. |
author_facet | Woods, Erik J. Sherry, Aubrey M. Woods, John R. Hardin, James W. LaFontaine, Michael Brandacher, Gerald Johnstone, Brian H. |
author_sort | Woods, Erik J. |
collection | PubMed |
description | BACKGROUND: Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking system will be to manage the prolonged ischemia times that are inevitable when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. Our objectives were to: (a) quantify, under realistic field conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) identify ischemia-time boundaries beyond which HSPC quality is adversely affected; (c) investigate whole-body cooling as a strategy for preserving cell quality; and (d) investigate processing experience as a variable affecting quality. METHODS: Seventy-five bones from 62 donors were analyzed for CD34+ viability following their exposure to various periods of warm-ischemia time (WIT), cold-ischemia time (CIT), and body-cooling time (BCT). Regression models were developed to quantify the independent associations of WIT, CIT, and BCT, with the viability and function of recovered HSPCs. RESULTS: Results demonstrate that under “real-world” scenarios: (a) combinations of warm- and cold-ischemia times favorable to the recovery of high-quality HSPCs are achievable (e.g., CD34+ cell viabilities in the range of 80–90% were commonly observed); (b) body cooling prior to bone recovery is detrimental to cell viability (e.g., CD34+ viability < 73% with, vs. > 89% without body cooling); (c) vertebral bodies (VBs) are a superior source of HSPCs compared to ilia (IL) (e.g., %CD34+ viability > 80% when VBs were the source, vs. < 74% when IL were the source); and (d) processing experience is a critical variable affecting quality. CONCLUSIONS: Our models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards. |
format | Online Article Text |
id | pubmed-7405448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74054482020-08-07 Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank Woods, Erik J. Sherry, Aubrey M. Woods, John R. Hardin, James W. LaFontaine, Michael Brandacher, Gerald Johnstone, Brian H. J Transl Med Research BACKGROUND: Deceased organ donors represent an untapped source of therapeutic bone marrow (BM) that can be recovered in 3–5 times the volume of that obtained from living donors, tested for quality, cryopreserved, and banked indefinitely for future on-demand use. A challenge for a future BM banking system will be to manage the prolonged ischemia times that are inevitable when bones procured at geographically-dispersed locations are shipped to distant facilities for processing. Our objectives were to: (a) quantify, under realistic field conditions, the relationship between ischemia time and the quality of hematopoietic stem and progenitor cells (HSPCs) derived from deceased-donor BM; (b) identify ischemia-time boundaries beyond which HSPC quality is adversely affected; (c) investigate whole-body cooling as a strategy for preserving cell quality; and (d) investigate processing experience as a variable affecting quality. METHODS: Seventy-five bones from 62 donors were analyzed for CD34+ viability following their exposure to various periods of warm-ischemia time (WIT), cold-ischemia time (CIT), and body-cooling time (BCT). Regression models were developed to quantify the independent associations of WIT, CIT, and BCT, with the viability and function of recovered HSPCs. RESULTS: Results demonstrate that under “real-world” scenarios: (a) combinations of warm- and cold-ischemia times favorable to the recovery of high-quality HSPCs are achievable (e.g., CD34+ cell viabilities in the range of 80–90% were commonly observed); (b) body cooling prior to bone recovery is detrimental to cell viability (e.g., CD34+ viability < 73% with, vs. > 89% without body cooling); (c) vertebral bodies (VBs) are a superior source of HSPCs compared to ilia (IL) (e.g., %CD34+ viability > 80% when VBs were the source, vs. < 74% when IL were the source); and (d) processing experience is a critical variable affecting quality. CONCLUSIONS: Our models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards. BioMed Central 2020-08-05 /pmc/articles/PMC7405448/ /pubmed/32758261 http://dx.doi.org/10.1186/s12967-020-02470-1 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Woods, Erik J. Sherry, Aubrey M. Woods, John R. Hardin, James W. LaFontaine, Michael Brandacher, Gerald Johnstone, Brian H. Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title | Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title_full | Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title_fullStr | Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title_full_unstemmed | Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title_short | Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
title_sort | ischemia considerations for the development of an organ and tissue donor derived bone marrow bank |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405448/ https://www.ncbi.nlm.nih.gov/pubmed/32758261 http://dx.doi.org/10.1186/s12967-020-02470-1 |
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