Abstract
Mesenchymal stromal cells (MSCs) can be derived from various tissue sources, such as the bone marrow (BMSCs), adipose tissue (ADSCs), umbilical cord (UC-MSCs) and umbilical cord blood (UCB-MSCs). Clinical trials have been conducted to investigate the potential of MSCs in ameliorating neonatal diseases, including bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). In preclinical studies, MSC therapy has been tested for the treatment of various neonatal diseases affecting the heart, eye, gut, and brain as well as sepsis. Up to date, the number of clinical trials using MSCs to treat neonatal diseases is still limited. The data reported thus far positioned MSC therapy as safe with positive outcomes. However, most of these trials are still preliminary and generally smaller in scale. Larger trials with more appropriate controls and a longer follow-up period need to be conducted to prove the safety and efficacy of the therapy more conclusively. This review discusses the current application of MSCs in treating neonatal diseases, its mechanism of action and future direction of this novel therapy, including the potential of using MSC-derived extracellular vesicles instead of the cells to treat various clinical conditions in the newborn.
Highlights
Mesenchymal stromal cells (MSCs) possess several unique properties which render them an ideal candidate for cell-based therapy in various neonatal diseases
The results indicated that all sources of stem cells reduced the incidence and severity of experimental necrotizing enterocolitis (NEC)
Results showed that stromal thickness increased significantly and transparency improved in MSC-treated corneas as early as 8 weeks after treatment compared to the control group
Summary
Mesenchymal stromal cells (MSCs) possess several unique properties which render them an ideal candidate for cell-based therapy in various neonatal diseases. Alvarez-Fuente et al reported suppression of pro-inflammatory as well as improvement in pulmonary hypertension and diminished levels of surfactant protein D (SP-D) expression, a biomarker for lung injury, in 2 preterm infants given multiple dosages of allogeneic BMSCs intravenously [17] Both patients received stem cell therapy at the very advanced stages of BPD and passed away 6 weeks after the initiation of MSC therapy. Lin et al reported improvement in respiratory functions after intratracheal administration of maternal BMSC (6.25 × 106 cells/kg) in a 10-month old preterm infant with BPD that developed acute respiratory distress syndrome (ARDS) [18] Results from these clinical studies suggested that the beneficial effects of MSCs might be attributed to paracrine effects that stimulate alveolarization and vascularization rather than cell engraftment and proliferation as traces of donor cells in the recipients were absent. Frequency of Follow up Safety outcome Key efficacy outcome cell period administration
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