Abstract
BackgroundDeceased 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.MethodsSeventy-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.ResultsResults 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.ConclusionsOur models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards.
Highlights
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
Our analyses show that high-quality, functional hematopoietic stem and progenitor cells (HSPCs) can be obtained from deceased donors even after recovered bones are subjected to cumulative warm- and cold-ischemia times exceeding 40 h, provided that body cooling, which is shown to be detrimental to viability, is avoided
The statistical distributions of individual ischemia-time components warm-ischemia time (WIT), cold-ischemia time (CIT), and body cooling time (BCT) ordered by total ischemia time, for each of 62 donors is provided in the Additional file: Appendix S3, Figure S1
Summary
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. Deceased-donor bone marrow (BM) represents a large, untapped source of hematopoietic stem and progenitor cells (HSPCs) that could be cryopreserved and banked for future on-demand use in bone marrow transplant (BMT) procedures. A donor BM bank would provide a repository for future tolerance induction and immunomodulation procedures that use delayed protocols. Such procedures have already been proven successful in non-human primates [6, 7]. Organizing an integrated organ-donor BM procurement and banking system that capitalizes on this infrastructure, will require coordinated efforts, involving the recovery and safe shipment of biological material to specialized BM cell-processing centers appropriately scaled for clinical production
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