为极早产儿自体细胞治疗应用采集脐带血的可行性。

Feasibility of cord blood collection for autologous cell therapy applications in extremely preterm infants.

作者信息

Zhou Lindsay, McDonald Courtney A, Yawno Tamara, Penny Tayla, Miller Suzanne L, Jenkin Graham, Malhotra Atul

机构信息

Department of Pediatrics, Monash University, Melbourne, Australia; The Ritchie Center, Hudson Institute of Medical Research, Melbourne, Australia; Monash Newborn, Monash Children's Hospital, Melbourne, Australia.

The Ritchie Center, Hudson Institute of Medical Research, Melbourne, Australia; Department of Obstetrics and Gynecology, Monash University, Melbourne, Australia.

出版信息

Cytotherapy. 2023 May;25(5):458-462. doi: 10.1016/j.jcyt.2023.01.001. Epub 2023 Feb 4.

DOI:10.1016/j.jcyt.2023.01.001

PMID:36740465

Abstract

BACKGROUND AIMS

Umbilical cord blood (UCB)-derived cells show strong promise as a treatment for neonatal brain injury in pre-clinical models and early-phase clinical trials. Feasibility of UCB collection and autologous administration is reported for term infants, but data are limited for preterm infants. Here the authors assessed the feasibility of UCB-derived cell collection for autologous use in extremely preterm infants born at less than 28 weeks, a population with a high incidence of brain injury and subsequent neurodisability.

METHODS

In a prospective study at a tertiary hospital in Melbourne, Australia, UCB was collected from infants born at less than 28 weeks and processed to obtain total nucleated cells (TNCs), CD34+ cells, mononuclear cells and cell viability via fluorescence-activated cell sorting prior to cryopreservation. Feasibility was pre-defined as volume adequate for cryopreservation (>9 mL UCB collected) and >25 × 10 TNCs/kg retrieved.

RESULTS

Thirty-eight infants (21 male, 17 female) were included in the study. Twenty-four (63.1%) were delivered via cesarean section, 30 (78.9%) received delayed cord clamping before collection and 11 (28.9%) were a multiple birth. Median (interquartile range [IQR]) gestational age was 26.0 weeks (24.5-27.5) and mean (standard deviation) birth weight was 761.5 g (221.5). Median (IQR) UCB volume collected was 19.1 mL/kg (10.5-23.5), median (IQR) TNC count was 105.2 × 10/kg (57.4-174.4), median (IQR) CD34+ cell count was 1.5 × 10/kg (0.6-2.1) and median (IQR) cell viability pre-cryopreservation was 95% (92.1-96.0). Feasibility of collection volume and cell count suitable for cell cryopreservation was achieved in 27 (71%) and 28 (73.6%) infants, respectively.

CONCLUSIONS

UCB-derived cell collection adequate for cryopreservation and subsequent autologous reinfusion was achieved in 70% of extremely preterm infants. Extremely preterm UCB demonstrated a higher CD34+:TNC ratio compared with published full-term values. Recruitment to demonstrate safety of UCB cell administration in extremely premature infants is ongoing in the CORD-SAFE study (trial registration no. ACTRN12619001637134).

摘要

背景目的

在临床前模型和早期临床试验中，脐带血（UCB）来源的细胞作为新生儿脑损伤的治疗方法显示出巨大潜力。足月婴儿脐带血采集及自体输注的可行性已有报道，但早产儿的数据有限。本文作者评估了出生孕周小于28周的极早产儿自体使用脐带血来源细胞采集的可行性，该人群脑损伤及后续神经残疾发生率较高。

方法

在澳大利亚墨尔本一家三级医院进行的一项前瞻性研究中，收集出生孕周小于28周婴儿的脐带血，在冷冻保存前通过荧光激活细胞分选处理以获得有核细胞总数（TNCs）、CD34 +细胞、单核细胞及细胞活力。可行性预先定义为采集的脐带血体积足以冷冻保存（采集的脐带血>9 mL）且回收的TNCs>25×10 /kg。

结果

38例婴儿（21例男性，17例女性）纳入研究。24例（63.1%）通过剖宫产分娩，30例（78.9%）在采集前接受延迟脐带结扎，11例（28.9%）为多胎妊娠。中位（四分位间距[IQR]）孕周为26.0周（24.5 - 27.5），平均（标准差）出生体重为761.5 g（221.5）。采集的脐带血中位（IQR）体积为19.1 mL/kg（10.5 - 23.5），TNCs计数中位（IQR）为105.2×10 /kg（57.4 - 174.4），CD34 +细胞计数中位（IQR）为1.5×10 /kg（0.6 - 2.1），冷冻保存前细胞活力中位（IQR）为95%（92.1 - 96.0）。分别有27例（71%）和28例（73.6%）婴儿实现了适合细胞冷冻保存的采集体积和细胞计数的可行性。