# Mesenchymal Stem Cell Therapy for Neurological Complications of Prematurity: A Narrative Review

## TL;DR

This paper reviews how mesenchymal stem cells may help treat neurological issues in premature infants by reducing inflammation and supporting tissue repair.

## Contribution

The paper highlights MSCs' paracrine signaling as a key mechanism and explores cell-free alternatives for safer therapy.

## Key findings

- MSCs improve oligodendrocyte maturation and reduce white matter injury in preclinical models.
- Early clinical trials show feasibility and short-term safety of MSC therapy in neonatal encephalopathy.
- MSC-derived extracellular vesicles may provide similar benefits with fewer safety concerns.

## Abstract

Background: Preterm birth is a leading cause of neonatal mortality and long-term disability worldwide. Injury in premature infants is demonstrated by disrupted organ development from inflammation, oxidative stress, hypoxia, and impaired vascular maturation. Current therapies largely provide supportive care and do not directly promote tissue regeneration. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential strategy to enhance endogenous repair across organ systems commonly affected by prematurity. Results: Evidence indicates that MSCs exert therapeutic effects primarily through transient paracrine signaling rather than long-term engraftment. Following administration, MSCs release cytokines, growth factors, and extracellular vesicles that reduce inflammation, promote angiogenesis, and support tissue repair. In preclinical models of neonatal brain injury, MSC therapy has been associated with improved oligodendrocyte maturation and reduced white matter injury. Early clinical trials in neonatal encephalopathy demonstrate feasibility and short-term safety of both autologous and allogeneic cell products. However, studies remain limited by small sample sizes and short follow-up. Cell-free approaches using MSC-derived extracellular vesicles may offer similar biological benefits with potentially lower safety and regulatory concerns. Conclusions: MSC-based therapies represent a promising regenerative approach for complications of prematurity. Rigorous, large-scale trials with standardized protocols and long-term follow-up are necessary to clarify efficacy, optimize delivery strategies, and define safety in this vulnerable population.