Mesenchymal stem cells in the pathogenesis and treatment of bronchopulmonary dysplasia: a clinical review

Abstract

Advances in neonatal medicine have led to increased survival of infants born at the limits of viability, resulting in an increased incidence of bronchopulmonary dysplasia (BPD). BPD is a chronic lung disease of premature infants characterized by the arrest of alveolarization, fibroblast activation, and inflammation. BPD leads to significant morbidity and mortality in the neonatal period and is one of the leading causes of chronic lung disease in children. The past decade has brought a surge of trials investigating cellular therapies for the treatment of pulmonary diseases. Mesenchymal stem cells (MSCs) are of particular interest because of their ease of isolation, low immunogenicity, and antiinflammatory and reparative properties. Clinical trials of MSCs have demonstrated short-term safety and tolerability; however, studies have also shown populations of MSCs with adverse pro-inflammatory and myofibroblastic characteristics. Cell-based therapies may represent the next breakthrough therapy for the treatment of BPD, however, there remain barriers to implementation as well as gaps in knowledge of the role of endogenous MSCs in the pathogenesis of BPD. Concurrent high-quality basic science, translational, and clinical studies investigating the fundamental pathophysiology underlying BPD, therapeutic mechanisms of exogenous MSCs, and logistics of translating cellular therapies will be important areas of future research.

Timing of erythropoietin modified mesenchymal stromal cell transplantation for the treatment of experimental bronchopulmonary dysplasia

“…We have shown that MSCs in combination with EPO could attenuate lung fibrosis induced by high oxygen through inhibition of TGF‐β1/Smad signalling . Recent studies suggest that inflammation response also plays a major role in the development of BPD, therefore, it is very necessary to study whether the MSCs and EPO combination therapy can more attenuate inflammation than MSCs transplantation alone. p38 MAPK acts upstream of LPS‐induced nuclear factor‐kappa B (NF‐κB), which is a key participant in the inflammation, immune response, and regulation of cell differentiation and apoptosis during acute lung injury .…”

Intratracheal Transplantation of Amnion-Derived Mesenchymal Stem Cells Ameliorates Hyperoxia-Induced Neonatal Hyperoxic Lung Injury via Aminoacyl-Peptide Hydrolase

“…Clinical studies investigating the appropriate dose of IT MSCs for treatment of BPD included doses of 1×10 7 and 2×10 7 cells/kg. Both doses appeared to be safe without increased short term or long-term adverse events (31,32). Multiple studies have investigated the efficacy of IT MSCs delivery in rat BPD model, and these have typically included doses of ∼10 5 cells per rat (33,34).…”

Use of Autologous Cord Blood Mononuclear Cells Infusion for the Prevention of Bronchopulmonary Dysplasia in Extremely Preterm Neonates: A Study Protocol for a Placebo-Controlled Randomized Multicenter Trial [NCT04440670]

“…As a convenient and safe source of stem cells, it could provide regrowth to underdeveloped lung tissue of preterm infants by providing more stem/progenitor cells. In addition, its paracrine effects help to improve lung function, vascularization of the airways, and reduce fibrosis, and therefore have considerable potential for reducing lung injury in preterm infants (35)(36)(37)(38)(39)(40). However, few studies have evaluated the effects of ACBMNC infusion for prevention of BPD in extremely preterm infants.…”