Prevention of LPS-induced acute respiratory distress syndrome in sheep by bone marrow-derived mesenchymal stem/stromal cells

Abstract

In this study, 10 male Shall sheep were used in two groups and bone marrow samples were collected and BM-MSCs isolated. Then experimental model of ARDS was induced by intrapulmonary injection of LPS to dose of 400 μg/kg. Twenty-four hours after LPS injection, 5×10 7 cells of BM-MSCs were autologous transferred in the group of treatment and 1ml PBS was infused in the group of control as intrapulmonary. Then, the symptoms of clinical, complete blood count, analysis of arterial blood gases and the concentrations of IL6,IL10,TNF-α,total protein, Ig M and albumin BAL were determined before and at times of 3,6,12,24,48,72, and 168 after transplantation/infusion. The results of the investigations 24 hours post-LPS injection(time 0) indicated the occurrence of acute in ammation which con rmed ARDS model. These changes included increase in RR, HR and RT, decrease in PO2 and SatO2 and increase in PCO2, WBC, neutrophils, macrophages, total protein, IL6, IL10, TNF-α, Ig M and albumin. But the stem/stromal cells transplantation reduced the severity of clinical signs induced by LPS, caused signi cant increase in PO 2 , SatO 2 and IL-10 and signi cant decrease in PCO 2 , the total protein, TNF-α, IL-6, Ig M, albumin, WBCs, neutrophils and macrophages at different times of sampling both in compared with before transplantation(time 0) and in compared with the group of control.While in the control group, in ammation continued until the end of the study. These results showed that BM-MSCs are able to reduce in ammation and have an important role in reconstruction of the damaged lung.

Mesenchymal Stromal Cells in Acute Respiratory Distress Syndrome: Shoulder Heavy Responsibilities, and a Long Way to Go

“…Second, the stem cell therapy dose for smoke inhalation injury is rarely reported. Allogeneic MSC single dose (6.1 × 10 6 MSCs per dose) in this study was much lower than those used in previous large-animal studies or clinical trials of ARDS (usually 1–10 million cells/kg, or even higher) ( 3 , 4 ). Moreover, I do not know whether the actual MSC dose in autologous BMAC (3 × 10 6 white blood cells and a mean of 56.6 × 10 6 platelets per dose) was equivalent to the allogeneic MSC dose.…”

Regenerative medicine in lung diseases: A systematic review

“…Aside from symptomatic therapy, no specific treatment for these diseases have been defined that would substantially improve short- and long-term outcomes. Positive effects in terms of reducing pulmonary edema and inflammation and improving gas exchange have been reported after cell treatment in experimentally induced ARDS in sheep ( 22 , 25 , 32 , 36 , 37 ). Currently, research on the effect of SC on the treatment of ARDS caused by respiratory viruses is particularly relevant due to the COVID-19 pandemic ( 67 , 90 , 92 ).…”

Small Ruminants and Its Use in Regenerative Medicine: Recent Works and Future Perspectives

“…To explore other respiratory diseases, sheep models have already been used in the studies of acute bronchial obstruction, regulation of surfactant proteins, infant respiratory distress syndrome using premature lambs and adult respiratory distress syndrome [95]. The use of MSCs in the treatment of pulmonary pathologies has already been explored in different studies involving sheep, with, for example, improved oxygenation and decreased pulmonary oedema in cases of bacterial pneumonia [99], decreased impact of endotoxins with attenuation of inflammation in acute respiratory distress syndrome [100][101][102] and attenuation of pulmonary microvascular hyperpermeability after smoke and hot air inhalation [103]. In a sheep model of endotoxemia treated with intrathecal implantation of BM-MSCs, easier management of acute respiratory distress, less inflammation and better histological parameters were observed [104].…”