Immunoregulatory effects of multipotent adult progenitor cells in a porcine ex vivo lung perfusion model

Abstract

BackgroundPrimary graft dysfunction (PGD) is considered to be the end result of an inflammatory response targeting the new lung allograft after transplant. Previous research has indicated that MAPC cell therapy might attenuate this injury by its paracrine effects on the pro-/anti-inflammatory balance. This study aims to investigate the immunoregulatory capacities of MAPC cells in PGD when administered in the airways.MethodsLungs of domestic pigs (n = 6/group) were subjected to 90 minutes of warm ischemia. Lungs were cold flushed, cannulated on ice and placed on EVLP for 6 hours. At the start of EVLP, 40 ml of an albumin-plasmalyte mixture was distributed in the airways (CONTR group). In the MAPC cell group, 150 million MAPC cells (ReGenesys/Athersys, Cleveland, OH, USA) were added to this mixture. At the end of EVLP, a physiological evaluation (pulmonary vascular resistance, lung compliance, PaO2/FiO2), wet-to-dry weight ratio (W/D) sampling and a multiplex analysis of bronchoalveolar lavage (BAL) (2 × 30 ml) was performed.ResultsPulmonary vascular resistance, lung compliance, PaO2/FiO2 and W/D were not statistically different at the end of EVLP between both groups. BAL neutrophilia was significantly reduced in the MAPC cell group. Moreover, there was a significant decrease in TNF-α, IL-1β and IFN-γ in the BAL, but not in IFN-α; whereas IL-4, IL-10 and IL-8 were below the detection limit.ConclusionsAlthough no physiologic effect of MAPC cell distribution in the airways was detected during EVLP, we observed a reduction in pro-inflammatory cytokines and neutrophils in BAL in the MAPC cell group. This effect on the innate immune system might play an important role in critically modifying the process of PGD after transplantation. Further experiments will have to elucidate the immunoregulatory effect of MAPC cell administration on graft function after transplantation.

Plasma‐Activated Substrate with a Tropoelastin Anchor for the Maintenance and Delivery of Multipotent Adult Progenitor Cells

“…Accordingly, the undelivered cells on the PIII‐treated and tropoelastin‐coated patches remain viable and can repopulate the polymer surface for subsequent transfer to skin. At the same time, the proliferating cells can serve as a resource of secreted growth factors and cytokines that promote healing . Therefore, while the number of cells initially delivered from unmodified and functionalized PU are similar, the potential for repeated cell expansion and transfer from the functionalized patches translates to a higher total amount of delivered cells from the same starting dose.…”

Machine perfusion of thoracic organs

“…In another study by the Leuven group, the immunoregulatory capacities of multipotent adult progenitor cells (MAPC) on PGD were investigated in a lung injury model when administered via the airways. Although physiologic parameters during 6 hours EVLP were not different between both study groups, neutrophilia in bronchoalveolar lavage (BAL) fluid was significantly reduced in the MAPC group compared to controls, accompanied with a significant decrease in TNF-α, IL-1β and IFN-γ in the BAL (168).…”

Evolving Trend of EVLP: Advancements and Emerging Pathways

“…Three hours of EVLP could reduce donor leukocyte transfer into the recipient and migration to lymph nodes, as well as diminished recipient T cell infiltration [105]. EVLP could further reduce inflammatory reaction related to a following PGD occurrence [106], although some extracorporeal life support is being used early in patients who have PGD [107]. reducing primary graft dysfunction incidence [108].…”