Mesenchymal stem cell therapy for bronchopulmonary dysplasia: current evidence and future directions—a narrative review
- 1Department of Pediatrics, University of Connecticut, Farmington, CT, USA
- 2Department of Cardiology, Westchester Medical Center and New York Medical College, Westchester, NY, USA
- 3Department of Medicine and Cardiology, Westchester Medical Center and New York Medical College, Westchester, NY, USA
Abstract
Background and Objective: Bronchopulmonary dysplasia (BPD) remains the most common long-term respiratory complication of extreme prematurity, with no disease-modifying therapy in routine clinical practice. Mesenchymal stem cells (MSCs) derived from umbilical cord (UC) blood have advanced further toward clinical translation than any other regenerative candidate for BPD. This review synthesizes the current clinical evidence for MSC therapy in BPD, focusing on trial results, safety, long-term outcomes, and emerging cell-free alternatives.
Methods: PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from January 2009 to June 2026 using MeSH and free-text terms for MSCs, BPD, and extracellular vesicles (EVs), restricted to English-language publications.
Key Content and Findings: Phase I trials across multiple institutions confirmed safety and feasibility of intratracheal and intravenous MSC administration in extremely preterm infants. The pivotal phase II randomized controlled trial did not meet its primary efficacy endpoint (death or moderate-to-severe BPD at 36 weeks) in the overall cohort. Preliminary sponsor-reported long-term follow-up data did not demonstrate a durable respiratory benefit at five years, including in a subgroup born at 23–24 weeks gestation; these findings have not yet been confirmed in a peer-reviewed primary publication. Ongoing trials are testing earlier prevention-oriented dosing (HULC-2; NCT07058025) and the first cell-free MSC-EV product, EXOB-001, in a combined phase I/II design (NCT06279741).
Conclusions: Available clinical data are reassuring with no major treatment-related safety signals to date, but no confirmed efficacy benefit has been demonstrated in completed trials. The field requires earlier prevention-oriented dosing windows, standardised cell-free EV products, and pivotal trials with pre-specified long-term endpoints built in from the start. MSC therapy for BPD remains investigational; enrolment in well-designed trials is the most appropriate pathway for eligible infants.
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BibTeX
@article{jha2026mesenchymal,
title = {{Mesenchymal stem cell therapy for bronchopulmonary dysplasia: current evidence and future directions—a narrative review}},
author = {Jagriti Jha and Siddhant Passey and Wilbert S. Aronow},
journal = {Annals of Translational Medicine},
year = {2026},
month = oct,
doi = {10.21037/atm-2026-0153},
url = {https://doi.org/10.21037/atm-2026-0153},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Mesenchymal stem cell therapy for bronchopulmonary dysplasia: current evidence and future directions—a narrative review
AU - Jagriti Jha
AU - Siddhant Passey
AU - Wilbert S. Aronow
PY - 2026
DA - 2026/10/22
JO - Annals of Translational Medicine
DO - 10.21037/atm-2026-0153
UR - https://doi.org/10.21037/atm-2026-0153
AB - Background and Objective: Bronchopulmonary dysplasia (BPD) remains the most common long-term respiratory complication of extreme prematurity, with no disease-modifying therapy in routine clinical practice. Mesenchymal stem cells (MSCs) derived from umbilical cord (UC) blood have advanced further toward clinical translation than any other regenerative candidate for BPD. This review synthesizes the current clinical evidence for MSC therapy in BPD, focusing on trial results, safety, long-term outcomes, and emerging cell-free alternatives. Methods: PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from January 2009 to June 2026 using MeSH and free-text terms for MSCs, BPD, and extracellular vesicles (EVs), restricted to English-language publications. Key Content and Findings: Phase I trials across multiple institutions confirmed safety and feasibility of intratracheal and intravenous MSC administration in extremely preterm infants. The pivotal phase II randomized controlled trial did not meet its primary efficacy endpoint (death or moderate-to-severe BPD at 36 weeks) in the overall cohort. Preliminary sponsor-reported long-term follow-up data did not demonstrate a durable respiratory benefit at five years, including in a subgroup born at 23–24 weeks gestation; these findings have not yet been confirmed in a peer-reviewed primary publication. Ongoing trials are testing earlier prevention-oriented dosing (HULC-2; NCT07058025) and the first cell-free MSC-EV product, EXOB-001, in a combined phase I/II design (NCT06279741). Conclusions: Available clinical data are reassuring with no major treatment-related safety signals to date, but no confirmed efficacy benefit has been demonstrated in completed trials. The field requires earlier prevention-oriented dosing windows, standardised cell-free EV products, and pivotal trials with pre-specified long-term endpoints built in from the start. MSC therapy for BPD remains investigational; enrolment in well-designed trials is the most appropriate pathway for eligible infants.
SN - 2305-5839
SN - 2305-5847
ER -