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Phase II Trial Suggests Safety and Feasibility of MSC Therapy for Chronic Lung Disease in Preterm Infants

Review of “Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Bronchopulmonary dysplasia, a chronic lung disease caused by prolonged periods of ventilator and oxygen therapy [1], remains a significant cause of mortality and long‐term respiratory and neurologic morbidities in premature infants. Recent research, including that from the groups of Won Soon Park (Sungkyunkwan University School of Medicine) and Ai‐Rhan Kim (University of Ulsan College of Medicine, Seoul, South Korea), has established mesenchymal stem cell (MSC) therapy as a potentially exciting means of inhibiting the development of bronchopulmonary dysplasia in human infants [2-7]. Furthermore, phase I clinical trials have suggested the safety and feasibility of intratracheal transplantations of human umbilical cord blood‐derived MSCs in affected premature infants, with no adverse respiratory, growth, or neurodevelopmental effects noted during a two-year follow‐up [8, 9].

In the hope of taking this therapy a step closer to widespread clinical use, the Park and Kim teams now report on a double‐blind, randomized placebo‐controlled phase II clinical trial assessing the therapeutic efficacy of human umbilical cord blood‐derived MSC transplantation for bronchopulmonary dysplasia in preterm infants. As described in a recent STEM CELLS Translational Medicine article, their results support a more focused, larger, and controlled phase II clinical trial [10].

The details of this trial reported by Ahn et al. include:

  • 66 preterm infants between 23 to 28 gestational weeks receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14 received MSCs or placebo
    • No significant differences in the clinical characteristics, including gestational age, birth weight, and Apgar scores (assesses the health of newborn children against infant mortality), existed between study groups
  • MSC treatment significantly reduced the levels of inflammatory cytokines (such as interleukin (IL)‐1β, IL‐6, IL‐8, tumor necrosis factor‐α) in the tracheal aspirate fluid
    • However, MSC transplantation failed to significantly improve primary outcomes (death or severe/moderate bronchopulmonary dysplasia
  • Subgroup analysis revealed a significant improvement of severe bronchopulmonary dysplasia (secondary outcome) in the 23 to 24 gestational week subgroup, but not in the 25 to 28 gestational week subgroup
    • As the study was underpowered to detect efficacy, a subsequent larger and controlled phase II clinical trial will focus on infants at 23 to 24 gestational weeks

Overall, this trial provides evidence for the safety and feasibility of intratracheal MSC transplantation in preterm infants, and they hope that the larger trial will support the effectiveness of this promising therapeutic approach. The authors also note that they have just completed the 5‐year long‐term follow‐up on the infants in this trial, and they hope to publish data regarding respiratory and developmental outcomes shortly.

For more on mesenchymal stem cell therapy as a treatment option for premature infants with bronchopulmonary dysplasia, stay tuned to the Stem Cells Portal!


References

  1. Baraldi E and Filippone M, Chronic Lung Disease after Premature Birth. New England Journal of Medicine 2007;357:1946-1955.
  2. Ahn SY, Chang YS, Kim SY, et al., Long-Term (Postnatal Day 70) Outcome and Safety of Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Neonatal Hyperoxic Lung Injury. Yonsei Med J 2013;54:416-424.
  3. Ahn SY, Chang YS, Sung DK, et al., Cell type-dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury. Cytotherapy 2015;17:1025-1035.
  4. Chang YS, Choi SJ, Ahn SY, et al., Timing of Umbilical Cord Blood Derived Mesenchymal Stem Cells Transplantation Determines Therapeutic Efficacy in the Neonatal Hyperoxic Lung Injury. PLOS ONE 2013;8:e52419.
  5. Chang YS, Choi SJ, Sung DK, et al., Intratracheal Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Dose-Dependently Attenuates Hyperoxia-Induced Lung Injury in Neonatal Rats. Cell Transplantation 2011;20:1843-1854.
  6. Chang YS, Oh W, Choi SJ, et al., Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Attenuate Hyperoxia-Induced Lung Injury in Neonatal Rats. Cell Transplantation 2009;18:869-886.
  7. Sutsko RP, Young KC, Ribeiro A, et al., Long-term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia-induced lung injury. Pediatric Research 2013;73:46-53.
  8. Chang YS, Ahn SY, Yoo HS, et al., Mesenchymal Stem Cells for Bronchopulmonary Dysplasia: Phase 1 Dose-Escalation Clinical Trial. The Journal of Pediatrics 2014;164:966-972.e6.
  9. Ahn SY, Chang YS, Kim JH, et al., Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia. The Journal of Pediatrics 2017;185:49-54.e2.
  10. Ahn SY, Chang YS, Lee MH, et al., Stem cells for bronchopulmonary dysplasia in preterm infants: A randomized controlled phase II trial. STEM CELLS Translational Medicine 2021;10:1129-1137.