Cell therapy for the treatment of sepsis and acute respiratory distress syndrome

Abstract

Sepsis and acute respiratory distress syndrome (ARDS) are life threating diseases with high mortality and morbidity in all the critical care units around the world. After decades of research, and numerous pre-clinical and clinical trials, sepsis and ARDS remain without a specific and effective pharmacotherapy and essentially the management remains supportive. In the last years cell therapies gained potential as a therapeutic treatment for ARDS and sepsis. Based on numerous pre-clinical studies, there is a growing evidence of the potential benefits of cell based therapies for the treatment of sepsis and ARDS. Several cell types are used in the last years for the treatment of both syndromes showing high efficiency. Embryonic stem cells (ESC), multipotent stem (or stromal) cells (MSC) and epithelial progenitors cells (EpPC) have been used for both diseases. Nowadays, the major part of the pre-clinical studies are using MSC, however other relevant groups are also using induced pluripotent stem cells (iPSC) for the treatment of both syndromes and alveolar type II cells for ARDS treatment. Numerous questions need further study including: determining the best source for the progenitor cells isolation, their large scale production and cryopreservation. Also, the heterogeneity of patients with sepsis and ARDS is massive, and establish a target population or the stratification of the patients will help us to determine better the therapeutic effect of these cell therapies. In this review we are going to describe briefly the different cell types, their potential sources and characteristics and mechanism of action. Here, also we elucidate the results of several pre-clicinical and clinical studies in ARDS and in sepsis and the future directions of these studies.

Comparative Effects of Umbilical Cord- and Menstrual Blood-Derived MSCs in Repairing Acute Lung Injury

“…Although ALI pathophysiology and treatments have been investigated in many studies, effective pharmacotherapies or therapeutic strategies are limited [ 11 ]. MSCs may be a promising alternative for treating lung diseases [ 12 , 13 ], as increasing evidence supports the therapeutic effects of MSCs in pulmonary fibrosis, bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and ALI. Recent studies have also shown that transplantation of MSCs from the bone marrow, umbilical cord (UC), menstrual blood (MB), and adipose tissue can attenuate lung injury and inflammatory responses [ 14 – 16 ].…”

From sepsis to acute respiratory distress syndrome (ARDS): emerging preventive strategies based on molecular and genetic researches

“…Diffuse alveolar damage is regarded as the histological hallmark of the first and acute phase of ARDS. Due to vascular leakage, alveolar epithelial damage and the accumulation of free fluid, the capacity for oxygen exchange decreases and leads to acute respiratory failure that subsequently develops into ARDS [30]. Thus, strategies targeting sepsis progression and cut the connection of the inflammatory network at an appropriate time to maintain the integrity of the vascular barrier integrity are urgently needed.…”

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

“…Currently, there is no specific treatment for septic shock and the management of this devastating complication of serious infections remains supportive. However, the following measures should be taken into consideration: early identification, fluid resuscitation, prompt institution of antibiotic therapy, control of the source of infection, circulatory support, and lung protection by mechanical ventilation [48,49,52,53].…”

“…Based on numerous preclinical studies, cell-based therapies are potentially beneficial in the treatment of septic shock and ARDS. However, various types of stem cells including embryonic stem cells, MSCs, and induced pluripotent stem cells have been used in the treatment of sepsis and ARDS, but MSCs are the most commonly used stem cells in septic shock [53]. In patients with septic shock complicated by acute lung injury (ALI) and ARDS, the paracrine factors secreted by MSCs can: mediate endothelial and epithelial permeability, and increase alveolar fluid clearance in addition to other mechanisms that reduce the complications of septic shock [54].…”