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Placenta-derived Stem Cells: A New Means to Treat Chronic Lung Disease in Premature Infants?

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Review of “First‐In‐Human Administration of Allogeneic Amnion Cells in Premature Infants with Bronchopulmonary Dysplasia: A Safety Study” from STEM CELLS Translational Medicine by Stuart P. Atkinson

Bronchopulmonary dysplasia (BPD), which entails impaired vascular development and alveolarization and lung inflammation [1], remains a common complication for premature babies [2]. Furthermore, we do not currently possess an effective means to cure BPD, and so the development of targeted therapies for BPD represents a research priority [3]. One clinical trial recently reported on the safety and tolerability of allogeneic human umbilical cord‐derived mesenchymal stem cells (MSCs) in premature babies at risk of developing BPD [4], suggesting the potential utility of additional stem cell-based therapies.

Now, researchers from the laboratory of Euan M. Wallace (Monash University, Clayton, Victoria, Australia) report the results of their first‐in‐human phase I trial to assess the safety and tolerability of allogeneic human amnion epithelial cells (hAECs) in premature babies with established BPD. The derivation of hAECs from discarded placenta membranes provides clinically relevant numbers of MSC-like cells [5] that can prevent the development of certain hallmarks of BPD in a preclinical model of the disease [6]. 

In STEM CELLS Translational Medicine, Lim et al. now report on the safety of allogeneic hAEC infusions in infants with established BPD, justifying future randomized clinical trials to assess efficacy [7].

Here are the details of this new study of placenta-derived stem cells as a new means to treat chronic lung disease in premature infants:

  • The single‐center, open‐label phase I trial intravenously administered one million allogeneic hAECs per kilogram bodyweight to six premature infants with BPD
    • While hAEC administration to the first infant led to a transient cardiorespiratory compromise consistent with a pulmonary embolic event, no overall adverse reaction occurred and the infant was discharged at one year of age and assessed again after two years
    • The introduction of an inline filter, the reduction of cell concentration, and a reduction in cell infusion rate nullified adverse events during infusion in the other infants
  • The authors observed no adverse events related to cell administration
    • One infant, who had never been successfully extubated since birth, died one month after cell administration due to multiorgan failure related to a cardiorespiratory collapse related to accidental extubation and not to cell administration

This encouraging study, which indicates safety and tolerability of placenta-derived stem cells, will soon be complemented by the report of longer‐term safety outcomes after completion of 2 years of follow‐up of the five infants (expected in 2019). These results will hopefully encourage the organization of randomized, placebo‐controlled dose‐escalation trials to assess efficacy in the hope of constructing effective cellular therapies for the prevention and treatment of chronic neonatal conditions.

For all the future related studies on placenta-derived stem cell therapy for BPD, stay tuned to the Stem Cells Portal.

References

  1. Baker CD and Alvira CM, Disrupted lung development and bronchopulmonary dysplasia: opportunities for lung repair and regeneration. Current opinion in pediatrics 2014;26:306.
  2. Jobe AH and Bancalari E, Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9.
  3. McEvoy CT, Jain L, Schmidt B, et al., Bronchopulmonary dysplasia: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases. Ann Am Thorac Soc 2014;11 Suppl 3:S146-53.
  4. Chang YS, Ahn SY, Yoo HS, et al., Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr 2014;164:966-972.e6.
  5. Murphy S, Rosli S, Acharya R, et al., Amnion epithelial cell isolation and characterization for clinical use. Curr Protoc Stem Cell Biol 2010;Chapter 1:Unit 1E.6.
  6. Vosdoganes P, Hodges RJ, Lim R, et al., Human amnion epithelial cells as a treatment for inflammation-induced fetal lung injury in sheep. Am J Obstet Gynecol 2011;205:156.e26-33.
  7. Lim R, Malhotra A, Tan J, et al., First-In-Human Administration of Allogeneic Amnion Cells in Premature Infants With Bronchopulmonary Dysplasia: A Safety Study. STEM CELLS Translational Medicine 2018;7:628-635.