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Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
Erik John Woods
Ossium Health, Inc.
Corresponding Author
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This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Translational Medicine.
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.
Keywords
deceased-donor bone marrow, bone marrow banking, bone marrow ischemia time, hematopoietic stem cell transplant
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CURRENT STATUS: Published
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Posted 17 Jun, 2020
Published
On 05 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 05 Jul, 2020
Review #2 received
Received 03 Jul, 2020
Review #1 received
Received 28 Jun, 2020
Reviewer #2 agreed
On 26 Jun, 2020
Reviewers invited
Invitations sent on 22 Jun, 2020
Reviewer #1 agreed
On 22 Jun, 2020
Editor assigned
On 15 Jun, 2020
Submission checks complete
On 14 Jun, 2020
Editor invited
On 14 Jun, 2020
No comments provided
Review #1 received
Received 21 May, 2020
Editorial decision: Major revision
On 21 May, 2020
Review #2 received
Received 17 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 30 Apr, 2020
Editor assigned
On 27 Apr, 2020
Editor invited
On 26 Apr, 2020
Submission checks complete
On 24 Apr, 2020
First submitted
On 23 Apr, 2020
Metrics
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PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
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This preprint is under consideration at Journal of Translational Medicine. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Ischemia considerations for the development of an organ and tissue donor derived bone marrow bank
Erik John Woods
Ossium Health, Inc.
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 17 Jun, 2020
Published
On 05 Aug, 2020
No community comments so far
Editorial decision: Minor revision
On 05 Jul, 2020
Review #2 received
Received 03 Jul, 2020
Review #1 received
Received 28 Jun, 2020
Reviewer #2 agreed
On 26 Jun, 2020
Reviewers invited
Invitations sent on 22 Jun, 2020
Reviewer #1 agreed
On 22 Jun, 2020
Editor assigned
On 15 Jun, 2020
Submission checks complete
On 14 Jun, 2020
Editor invited
On 14 Jun, 2020
No comments provided
Review #1 received
Received 21 May, 2020
Editorial decision: Major revision
On 21 May, 2020
Review #2 received
Received 17 May, 2020
Reviewer #2 agreed
On 06 May, 2020
Reviewer #1 agreed
On 04 May, 2020
Reviewers invited
Invitations sent on 30 Apr, 2020
Editor assigned
On 27 Apr, 2020
Editor invited
On 26 Apr, 2020
Submission checks complete
On 24 Apr, 2020
First submitted
On 23 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Translational Medicine.
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.
Figure 1
Figure 2