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

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

doi:10.1016/j.jcyt.2023.01.001

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

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

Authors

Lindsay Zhou¹, Courtney A McDonald², Tamara Yawno³, Tayla Penny⁴, Suzanne L Miller², Graham Jenkin², Atul Malhotra⁵

Affiliations

¹ 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. Electronic address: lindsay.zhou1@monash.edu.
² The Ritchie Center, Hudson Institute of Medical Research, Melbourne, Australia; Department of Obstetrics and Gynecology, Monash University, Melbourne, Australia.
³ Department of Pediatrics, Monash University, Melbourne, Australia; The Ritchie Center, Hudson Institute of Medical Research, Melbourne, Australia; Department of Obstetrics and Gynecology, Monash University, Melbourne, Australia.
⁴ The Ritchie Center, Hudson Institute of Medical Research, Melbourne, Australia.
⁵ 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.

PMID: 36740465
DOI: 10.1016/j.jcyt.2023.01.001

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 × 10⁶ 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 × 10⁶/kg (57.4-174.4), median (IQR) CD34+ cell count was 1.5 × 10⁶/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).

Keywords: autologous cell therapy; brain injury; cell therapy; neonatal cell therapy; regenerative medicine; umbilical cord blood cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cesarean Section
Feasibility Studies
Female
Fetal Blood*
Humans
Infant
Infant, Extremely Premature*
Infant, Newborn
Male
Pregnancy
Prospective Studies

Associated data

ANZCTR/ACTRN12619001637134