Woods Erik J, Sherry Aubrey M, Woods John R, Hardin James W, LaFontaine Michael, Brandacher Gerald, Johnstone Brian H
Ossium Health, Inc., 5742 W. 74th St, Indianapolis, IN, 46278, USA.
Department of Biomedical Sciences, College of Osteopathic Medicine, Marian University, 3200 Cold Spring Rd, Indianapolis, IN, 46222, USA.
J Transl Med. 2020 Aug 5;18(1):300. doi: 10.1186/s12967-020-02470-1.
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.
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 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.
Our models can be used by an emerging BM banking system to formulate ischemia-time tolerance limits and data-driven HSPC quality-acceptance standards.
已故器官捐献者是治疗性骨髓（BM）的一个未开发来源，其可获取的骨髓量是活体捐献者的3至5倍，可对其进行质量检测、冷冻保存，并无限期储存以供未来按需使用。未来骨髓库系统面临的一个挑战将是应对长时间的缺血时间，当从地理上分散的地点获取的骨骼被运往遥远的设施进行处理时，缺血时间不可避免。我们的目标是：（a）在实际现场条件下，量化缺血时间与源自已故捐献者骨髓的造血干细胞和祖细胞（HSPCs）质量之间的关系；（b）确定HSPC质量受到不利影响的缺血时间界限；（c）研究全身冷却作为一种保存细胞质量的策略；（d）研究处理经验作为影响质量的一个变量。
对来自62名捐献者的75块骨骼在经历不同时长的热缺血时间（WIT）、冷缺血时间（CIT）和身体冷却时间（BCT）后，分析其CD34 +活力。建立回归模型以量化WIT、CIT和BCT与回收的HSPCs活力和功能之间的独立关联。
结果表明，在“现实世界”场景下：（a）可实现有利于高质量HSPCs回收的热缺血和冷缺血时间组合（例如，常见CD34 +细胞活力在80 - 90%范围内）；（b）骨骼回收前的身体冷却对细胞活力有害（例如，有身体冷却时CD34 +活力< 73%，无身体冷却时> 89%）；（c）与髂骨（IL）相比，椎体（VBs）是HSPCs的优质来源（例如，以VBs为来源时%CD34 +活力> 80%，以IL为来源时< 74%）；（d）处理经验是影响质量的关键变量。
我们的模型可供新兴的骨髓库系统用于制定缺血时间耐受限度和数据驱动的HSPC质量验收标准。
