Mesenchymal stem cell-derived secretomes for therapeutic potential of premature infant diseases

Abstract

Preterm birth is a complex syndrome and remains a substantial public health problem globally. Its common complications include periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC) and retinopathy of prematurity (ROP). Despite great advances in the comprehension of the pathogenesis and improvements in neonatal intensive care and associated medicine, preterm birth-related diseases remain essentially without adequate treatment and can lead to high morbidity and mortality. The therapeutic potential of mesenchymal stem/stromal cells (MSCs) appears promising as evidenced by their efficacy in preclinical models of pathologies relevant to premature infant complications. MSC-based therapeutic efficacy is closely associated with MSC secretomes and a subsequent paracrine action response to tissue injuries, which are complex and abundant in response to the local microenvironment. In the current review, we summarize the paracrine mechanisms of MSC secretomes underlying diverse preterm birth-related diseases, including PVL, BPD, NEC and ROP, are summarized, and focus is placed on MSC-conditioned media (CM) and MSC-derived extracellular vesicles (EVs) as key mediators of modulatory action, thereby providing new insights for future therapies in newborn medicine.lung function and help to remove the ventilator as soon as possible [12]. However, many studies have reported that glucocorticoid can increase the risk of adverse reactions, such as those by the nervous system, in the early or late stages, and its dose and course of treatment are not certain [13,14]. In terms of surgical treatment, preterm infants with surgical NEC are at risk of significant growth reduction and neurodevelopmental impairment (NDI), including cerebral palsy, deafness and blindness [15,16]. These sequelae and complications of prematurity-related diseases affect not only the neonatal period, but also infancy and childhood, and even adolescence and adulthood [17][18][19]. Currently, although various treatment methods have been found to achieve certain curative effects, there still exist several side effects and disputes above. Thus, it is necessary to explore and develop new therapies for the treatment and prevention of premature infant diseases.Accumulating studies have established the importance and feasibility of stem cell-based therapies to ameliorate many degenerative and inflammatory diseases. Among these stem/progenitor cell types, mesenchymal stem/stromal cells (MSCs) have received more extensive attention because they are easily extracted, exert anti-inflammatory effects, have low immunogenicity and can renew themselves. The therapeutic potential of MSCs has been demonstrated in many diseases such as cancer [20,21] and cardiovascular [22,23] and lung [24][25][26] diseases. MSCs also represent a promising and growing approach to the targeting of various pathological processes and cellular impairments underlying the major abnormalities in premature infant and preterm-associated neonatal diseases [27][28]...

Comparing the Therapeutic Potential of Stem Cells and their Secretory Products in Regenerative Medicine

“…Besides brain injuries, therapeutic effects of growth factors present in MSCs have also been investigated for other pathologic conditions such as cutaneous injury, whereby the use of AT-MSC secretome that contains VEGF, HGF, transforming growth factor β (TGF-β), and keratinocyte growth factor (KGF) was able to induce greater cellular proliferation, trigger cell migration, and decrease the wound size at a faster rate [91][92][93][94][95]. The positive impact of these diverse growth factors in promoting angiogenesis [96], regenerating muscle tissue [97], and reducing incidences of premature infant diseases such as periventricular leukomalacia, retinopathy of prematurity, bronchopulmonary dysplasia, and necrotizing enterocolitis [98] also has been implicated.…”

Indirect co-culture of lung carcinoma cells with hyperthermia-treated mesenchymal stem cells influences tumor spheroid growth in a collagen-based 3-dimensional microfluidic model

“…Additionally, this study found that the conditioned medium inhibited tumor proliferation for other cancer cell types, and it included a group of secreted factors that could be responsible for this. Cell-free conditioned media derived from MSCs can be enriched in growth factors, exosomes, cytokines and chemokines [47]. Even though the results obtained in our study showed that the AMMSC-CM has a pro-tumorigenic tendency, despite this difference, few studies have investigated the anti-tumor effects of these cells in 3D culture.…”

The Potential of Mesenchymal Stromal Cell as Therapy in Neonatal Diseases

“…These changes in brain tissue will disrupt the cognitive, adaptive, motor, and social functions in the infant. Unlike other brain diseases with some limited therapeutic option, there is no specific treatment for PVL except for expectant and supportive management ( 36 ). Thus, researchers have begun exploring the use of MSCs for the treatment of PVL.…”