The Therapeutic Potential of Stem Cells for Bronchopulmonary Dysplasia: “It’s About Time” or “Not so Fast” ?

Abstract

While the survival of extremely premature infants improved over the past decades, the rate of complications - especially for bronchopulmonary dysplasia (BPD) - remains unacceptably high. Over the past 50 years, no safe therapy has had a substantial impact on the incidence and severity of BPD. This may stem from the multifactorial disease pathogenesis and the increasing lung immaturity. Mesenchymal stromal cells (MSCs) display pleiotropic effects and showed promising results in neonatal rodents in preventing or rescuing lung injury without adverse effects. Early phase clinical trials are now underway to determine the safety and efficacy of this therapy in the extremely premature infants. This review summarizes our current knowledge about MSCs, their mechanism of action and the results of preclinical studies that provided the rationale for early phase clinical trials and discuss our remaining gaps in knowledge.

The First Allogeneic Transplantation of Human Umbilical Cord-derived Mesenchymal Stem/stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants

“…Therefore, MSC transplantation emerges as a promising therapy investigated in a recently reported phase I clinical trial (21). Two potential mechanisms supporting the action of MSCs in BPD patients are the immunological regulatory functions and the secretion of a wide range of growth factors, cytokines, and exosomes that are involved in the initiation of tissue regeneration (35,36). Despite the rapid evolution of MSC therapy forthe treatment of BPD, it is important to emphasize that cell-based therapies for lung regeneration are still in their infancy, and major knowledge gaps regardinghow these MSCs may be involved in the repair of the damaged lung remain to be addressed.…”

“…Despite the rapid evolution of MSC therapy forthe treatment of BPD, it is important to emphasize that cell-based therapies for lung regeneration are still in their infancy, and major knowledge gaps regardinghow these MSCs may be involved in the repair of the damaged lung remain to be addressed. Hence, a better understanding of the biological activity of MSCs and technological advances in the manufacturing of these cells couldsupport the development of such therapies in the near future (36).…”

Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies

“…MSCs are multipotent stem cells that can be isolated from many tissue types ( Ee and Thébaud, 2018 ); MSC therapy is the most extensively studied cell therapy for BPD in hyperoxia models. This cell therapy focus has been placed on MSCs owing to their pleiotropic effects of immune modulation, angiogenesis and anti-oxidant activity – key hallmarks of BPD ( Ee and Thébaud, 2018 ; Davis et al, 2012 ; Kuchroo et al, 2015 ; Dey et al, 2012 ). A concern with the use of certain stem cells is their ability to form non-cancerous tumors called teratomas upon in vivo administration ( Hentze et al, 2009 ; Gutierrez-Aranda et al, 2010 ).…”

Mesenchymal stem cells for the prevention of bronchopulmonary dysplasia

“…Human MSC must meet the following three criteria: (i) adherence to plastic when maintained in culture; (ii) positive expression of several antigens such as CD90, CD105, and CD73; and (iii) ability to differentiate into osteoblasts, adipocytes, and chondrocytes under in vitro inductive conditions . Clinical trials are now being performed in patients with diseases including not only BPD but also graft‐versus‐host disease after BM transplantation, systemic lupus erythematosus, Crohn's disease, diabetes mellitus, multiple sclerosis, amyotrophic lateral sclerosis, spinal cord injury, and liver failure due to cirrhosis and hepatitis B …”