Allogeneic administration of human umbilical cord-derived mesenchymal stem/stromal cells for bronchopulmonary dysplasia: preliminary outcomes in four Vietnamese infants

Abstract

Background Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the progression of lung development in four infants with established BPD. Methods UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge. Results No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the progressive reductions in fibrosis. Conclusions Allo-UC-MSC administration is safe in preterm infants with established BPD. Trial registration This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019).

Clinically relevant preservation conditions for mesenchymal stem/stromal cells derived from perinatal and adult tissue sources

“…However, the use of PBS, M199, culture media and DMEM are inappropriate for clinical and therapeutic treatment because they are not approved vehicles for safe infusion into patients. Therefore, in our study, NaCl and RL were chosen as the main base media for MSC preservation because they have been widely used in numerous clinical trials 3,8,21 . It was reported that MSCs maintained in saline or dextrose for more than 2 h exhibited significantly reductions in viability, CFU capacity and differentiation ability 22 .…”

“…Therefore, in our study, NaCl and RL were chosen as the main base media for MSC preservation because they have been widely used in numerous clinical trials. 3 , 8 , 21 It was reported that MSCs maintained in saline or dextrose for more than 2 h exhibited significantly reductions in viability, CFU capacity and differentiation ability. 22 Based on the theory of cell ion and osmotic homeostasis, cell viability is strongly regulated by the osmolality and electrolyte concentration of the extracellular environment.…”

“… 5 The lack of major histocompatibility (MHC) class II in combination with the expression of early embryonic surface markers in the naive form of these MSCs provides solid evidence for their multipotency and immunological privilege. 6 Accessibility, easy and reproducible expansion, safety and potential effective treatment are considered major advantages of MSC therapy in various diseases, including orthopaedic injuries, cardiovascular disease, 7 pulmonary disease (bronchopulmonary dysplasia), 8 , 9 graft‐vs.‐host disease 10 and autoimmune disease, 11 among others.…”

Human Adipose-Derived Mesenchymal Stromal Cells Exhibit High HLA-DR Levels and Altered Cellular Characteristics under a Xeno-free and Serum-free Condition

“…The xeno-free and serum-free medium PS has been used to manufacture ADMSCs and umbilical cord-derived MSCs in some clinical trials [34,40,41]. However, there is only limited data reporting the immunophenotype of MSCs in this medium so far.…”

Human Adipose-derived Mesenchymal Stromal Cells Exhibit High HLA-DR Levels and Altered Cellular Characteristics under a Xeno-free and Serum-free Condition

“…Univariate analyses were conducted using Spearman's rank correlation and Kruskal-Wallis test. Statistical analyses were performed using the R software version 3.6.1 by a statistician [39]. Plots were prepared using the software GraphPad Prism 5.0 (GraphPad Software, La Jolla, CA).…”