Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas

Abstract

Ischaemia impairs organ quality during preservation in a time‐dependent manner, due to a lack of oxygen supply. Its impact on pancreas and islet transplantation outcome has been demonstrated by a correlation between cold ischaemia time and poor islet isolation efficiency. Our goal in the present study was to improve pancreas and islet quality using a novel natural oxygen carrier (M101, 2 g/L), which has been proven safe and efficient in other clinical applications, including kidney transplantation, and for several pre‐clinical transplantation models. When M101 was added to the preservation solution of rat pancreas during ischaemia, a decrease in oxidative stress (ROS), necrosis (HMGB1), and cellular stress pathway (p38 MAPK)activity was observed. Freshly isolated islets had improved function when M101 was injected in the pancreas. Additionally, human pancreases exposed to M101 for 3 hours had an increase in complex 1 mitochondrial activity, as well as activation of AKT activity, a cell survival marker. Insulin secretion was also up‐regulated for isolated islets. In summary, these results demonstrate a positive effect of the oxygen carrier M101 on rat and human pancreas during preservation, with an overall improvement in post‐isolation islet quality.

A therapeutic oxygen carrier isolated from Arenicola marina decreased P. gingivalis induced inflammation and tissue destruction

“…Direct oxygenation of damaged tissue is a therapeutic strategy paving way for the use of oxygen carriers such as M101. Indeed, preservation and perfusion of rat and human pancreas (ex vivo) 32 and porcine kidneys (in vivo) 33 with M101 solution improved graft function and transplantation outcome. Interestingly, first M101 use in human clinical trial demonstrated that kidney preservation with M101 solution (1 g/L) before transplantation, improved graft survival and renal function.…”

“…Owing to this exceptional O 2 -binding capacity, M101 releases O 2 according to a simple gradient and possesses antioxidative properties. It also exhibits intrinsic superoxide dismutase (SOD)-like activity, preventing the occurrence of potentially harmful hemoglobin degradation products such as heme-protein-associated free radical species (ROS), or ROS related to ischemia in the solution 31 , 32 . These desirable properties of M101 open new vistas for its wide industrial and therapeutic applications.…”

“…These desirable properties of M101 open new vistas for its wide industrial and therapeutic applications. The efficacy of M101 used ex vivo or in vivo as an additive to preservation solutions for preventing ischemia/reperfusion injuries has already been demonstrated in preclinical studies in kidney 33 , heart 34 , pancreas 32 , lung 35 and liver 36 . In the context of inflammation control, supplementation with M101 has shown reduced inflammation and fibrosis in kidney epithelium during static preservation 34 .…”

Combating hypoxemia in COVID-19 patients with a natural oxygen carrier, HEMO2Life® (M101)

“…Furthermore, the size of this molecule is 250 times smaller than a human red blood cell, allowing it to diffuse in all areas of the microcirculation, without diffusing outside the vascular sector. This product has been the subject of numerous publications [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] . This worm is farmed in aquaculture in a very strict good manufacturer practice conditions under ISO-13485 regulation.…”

Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation

“…12 Similar results were reported in preclinical models of lung, heart, and pancreas graft preservation. [13][14][15][16] Recently, in a French clinical trial using kidney transplantation from deceased donors, M101 demonstrated safety and efficacy, drastically decreasing the rate of delayed graft function recovery from 26% to 7%. 17 However, M101 performance in cold-stored liver graft remains to be studied.…”