Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in preterm infants who have been treated with supplemental oxygen and mechanical ventilation. Despite major advances in perinatal and neonatal medicine, limited progress has been made in reducing BPD rates. The use of mesenchymal stem cells (MSC) is a promising and innovative therapy for several diseases because they are easy to extract and they have low immunogenicity, anti-inflammatory properties, and regenerative ability. According to several pre-clinical studies that have used BPD animal models, one mechanism of action for MSC in BPD is mainly due to the paracrine effects of MSC-derived humoral factors, such as interleukin (IL)-6, IL-8, vascular endothelial growth factor, collagen, and elastin, rather than the multilineage and regenerative capacities of MSC. Cell-free preparations derived from MSC, including conditioned media and exosomes, remain a pre-clinical technology despite their great clinical potential. A first-in-human clinical trial of MSC treatment for BPD was performed as a phase I dose-escalation trial using umbilical cord blood-derived MSC. That trial demonstrated the short-and long-term safety and feasibility of MSC, given that significantly reduced inflammatory marker expression was observed in tracheal aspirates. As of recently, several clinical trials of MSC use for BPD are ongoing or are planned in some countries to investigate the efficacy of MSC in the prevention or treatment of BPD in premature infants. Many clinicians are currently awaiting the results from these trials so that MSC can be used clinically for human BPD. 100 Unknown Cord blood Recruiting BPD, bronchopulmonary dysplasia; FiO 2 , fraction of inspired oxygen; MSC, mesenchymal stem cells.

Can Stem Cells Beat COVID-19: Advancing Stem Cells and Extracellular Vesicles Toward Mainstream Medicine for Lung Injuries Associated With SARS-CoV-2 Infections

“…Since the key for the treatment of SARS-CoV-2 infection lies in the management of the cytokine storm in the lungs, MSCs are well-suited considering their main mechanism of action is through their immunomodulatory and anti-inflammatory properties (Fatima et al, 2017). The safety profile and efficacy of MSCs are well-established based on the results from a number of completed clinical studies investigating the therapeutic potential of these therapies in lung diseases such as ARDS (Matthay et al, 2019; and bronchopulmonary dysplasia (Namba, 2019), cardiovascular diseases (Kim et al, 2015;Suvakov et al, 2020), diabetes (Thakkar et al, 2015;Cho et al, 2018), and spinal cord injury (Xu and Yang, 2019).…”

Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease

“…Bronchopulmonary dysplasia (BPD), a leading cause of morbidity and mortality in premature infants, is a chronic lung disease that is multifactorial in origin [35]. The lungs of infants with BPD are underdeveloped due to the arrest or delay of alveolar development and pulmonary angiogenesis.…”

“…These patients are at increased risk of pulmonary infection, inflammation, and injury throughout infancy and childhood. There is a significant body of research evaluating the utility of using MSCs as a possible therapy for BPD, as highlighted in several recent reviews [35][36][37]. However, given the success of MSC-derived EVs in other pulmonary diseases, there are now multiple studies looking at the role of MSC-derived EV as therapy for BPD.…”

Efficacy and safety of mesenchymal stem cells for the treatment of patients infected with COVID-19: a systematic review and meta-analysis protocol

“…The safety and effectiveness of MSC therapy have been well documented in several clinical studies including ARDS, bronchopulmonary dysplasia and cardiovascular diseases. [8][9][10][11][12] In a recent case study, a 65-year-old critically ill ventilator-ridden patient with COVID-19 was treated with allogeneic human umbilical cord MSCs (three infusions of 5×10 7 cells at an interval of 3 days) and the patient was off the ventilator and able to walk after the second infusion. No obvious side effects were observed.…”