Newborn Research Centre, Royal Women's Hospital, Melbourne, Victoria, Australia.
Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
Stem Cells Transl Med. 2021 May;10(5):773-780. doi: 10.1002/sctm.20-0281. Epub 2021 Jan 6.
Cell therapies for neonatal morbidities are progressing to early phase clinical trials. However, protocols for intravenous (IV) delivery of cell therapies to infants have not been evaluated. It has been assumed the cell dose prescribed is the dose delivered. Early in our clinical trial of human amnion epithelial cells (hAECs), we observed cells settling in the syringe and IV tubing used to deliver the suspension. The effect on dose delivery was unknown. We aimed to quantify this observation and determine an optimal protocol for IV delivery of hAECs to extremely preterm infants. A standard pediatric infusion protocol was modeled in the laboratory. A syringe pump delivered the hAEC suspension over 60 minutes via a pediatric blood transfusion set (200-μm filter and 2.2 mL IV line). The infusion protocol was varied by agitation methods, IV-line volumes (0.2-2.2 mL), albumin concentrations (2% vs 4%), and syringe orientations (horizontal vs vertical) to assess whether these variables influenced the dose delivered. The influence of flow rate (3-15 mL/h) was assessed after other variables were optimized. The standard infusion protocol delivered 17.6% ± 9% of the intended hAEC dose. Increasing albumin concentration to 4%, positioning the syringe and IV line vertically, and decreasing IV-line volume to 0.6 mL delivered 99.7% ± 13% of the intended hAEC dose. Flow rate did not affect dose delivery. Cell therapy infusion protocols must be considered. We describe the refinement of a cell infusion protocol that delivers intended cell doses and could form the basis of future neonatal cell delivery protocols.
细胞疗法治疗新生儿疾病正在进入早期临床试验阶段。然而，尚未评估将细胞疗法通过静脉（IV）途径递送给婴儿的方案。人们普遍认为，规定的细胞剂量就是实际递送给患者的剂量。在我们对人羊膜上皮细胞（hAEC）的临床试验早期，我们观察到细胞在用于输送混悬液的注射器和 IV 管中沉淀。这对剂量输送的影响尚不清楚。我们旨在量化这一观察结果，并确定将 hAEC 递送给极早产儿的最佳 IV 输注方案。在实验室中模拟了标准儿科输注方案。注射器泵以 60 分钟的时间通过儿科输血套装（200-μm 过滤器和 2.2 mL IV 管）输送 hAEC 混悬液。通过搅拌方法、IV 管体积（0.2-2.2 mL）、白蛋白浓度（2%比 4%）和注射器方向（水平与垂直）改变输注方案，以评估这些变量是否会影响剂量输送。在优化其他变量后，评估了流速（3-15 mL/h）的影响。标准输注方案输送了 17.6%±9%的预期 hAEC 剂量。将白蛋白浓度提高到 4%、将注射器和 IV 管垂直放置并将 IV 管体积减少到 0.6 mL，可输送 99.7%±13%的预期 hAEC 剂量。流速不影响剂量输送。必须考虑细胞治疗输注方案。我们描述了细胞输注方案的改进，该方案可输送预期的细胞剂量，并可能为未来的新生儿细胞输送方案奠定基础。
