Marque Bretagne

ADDITIVE TO HYPOTHERMIC GRAFT PRESERVATION SOLUTIONS

The annual number of transplants is broadly constantly increasing in France, from 4,945 in 2011 to 5,276 in 2021. However, this still falls well short of demand. In 2020, 26,001 patients were waiting for organs1. More than 900 people on the transplant waiting list died due to the lack of available organs.
Faced with this shortage, regulatory and health authorities have authorized the use of organs from older and older donors and from donors who suffered cardiac death. Organs from such donors are very sensitive to the ischemia-reperfusion cycle.

In the USA, more than 115,000 people are waiting for transplants2. Yet, a study showed that out of  8,800 organs 540 were considered as lost3.

During a transplant of “solid” organs, the organ removed is experiencing a sudden stop of blood supply and therefore the oxygen necessary for its survival (i.e. ischemia). It is then usually placed in a 4°C preservation solution to reduce its metabolism (Figure 1).

Ischemia/reperfusion can lead to lesions due to the lack of oxygenation of the graft, and these play an important role in the risk of primary rejection of the graft by the recipient. Ischemia/reperfusion can lead to lesions due to the lack of oxygenation of the graft, and these play an important role in the risk of primary rejection of the graft by the recipient.

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Figure 1: The ischemia-reperfusion cycle is one of the major problems of transplantation

The challenge is therefore major to provide solutions to limit these lesions and thus improve the quality of the grafts.

In this context, the HEMO2life® medical device developed by Hemarina represents a breakthrough innovation in the field of organ preservation. HEMO2life® is an additive to organ preservation solutions, allowing the graft to be oxygenated physiologically and thus considerably reducing the risk of graft rejection and extending the storage time of the grafts.

HEMO2life® has been tested on several pre-clinical models, and has been the subject of two clinical studies in kidney transplantation (Oxyop – NCT02652520 & Oxyop2 – NCT04181710)) led by Prof. Yannick Le Meur (CHRU Brest) and Prof. Benoît Barrou (APHP, Pitié-Salpêtrière Paris), including in total more than 550 patients.

A retrospective study (Oxyop4 – NCT05050513) has been carried out in order to follow-up Oxyop patients over 4 years. The results have showed a reduced delayed graft function  and a better survival of patients who have received a graft preserved with HEMO2life®

Another retrospective study, based on the comparison of Oxyop clinical  data and ASTRE database containing the clinical parameters of 6,584 patients after kidney transplantation, confirmed the positive results of the OXYOP study and suggested that the better recovery of renal function observed with HEMO2life® in the OXYOP study is due to a clear therapeutic benefit of HEMO2life® reducing DGF independently of Cold Ischemia Time (Le Meur et al., 2022, Artificial Organ,  46, 597-605).

Since 2018, HEMO2life® has also been used a couple of times in the context of major reconstructive surgeries and  complex grafts (composite tissue grafts).  

The immediate benefit of the widespread use of this technology would be twofold: to provide transplant surgeons with organs in excellent physiological conditions and provide better preservation conditions for the graft while it is in transit.
This would increase the time the organ could survive between the time of collection and transplantation to the recipient.

Today, harvested organs can only survive a few hours post removal, after which time they lose their metabolic functions and intrinsic quality (3-4 hours for a heart and 24 hours for a kidney). HEMO2 life® allows longer possible preservation time of the harvested organs, can be easily integrated into current hospital practices and could greatly facilitate the organisation of the transplant by giving medical staff more time to prepare the transplant.

1. Biomedicine Agency, press release, CRISTAL, 03/03/2021
2. Number of candidates for transplantation in the United States, Organ Procurement & Transplantation Network
https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#

3. The Organ Shortage Crisis in America , Flescher, Andrew , Washington, DC:  Georgetown University Press, 2018. 

Class III Medical Device (NB 2797)

HEMO2life® : Related Publications

Asong-Fontem, N., Panisello-Rosello, A., Lopez, A., Imai, K., Zal, F., Delpy, E., Rosello-Catafau, J., Adam, R. A Novel Oxygen Carrier (M101) Attenuates Ischemia-Reperfusion Injuries during Static Cold Storage in Steatotic Livers Int. J. Mol. Sci. - 2021 https://pubmed.ncbi.nlm.nih.gov/34445250/

Ali, A., Watanabe, Y., Galasso, M., Watanabe, T., Chen, M., Fan, E., Brochard, L., Ramadan, K., Ribeiro, RVP., Stansfield, W., Gokhale, H., Gazzalle, A., Waddell, T., Liu, M., Keshavjee, S., Cypel, M. An extracellular oxygen carrier during prolonged pulmonary preservation improves post-transplant lung function J Heart Lung Transplant. - 2020 https://www.ncbi.nlm.nih.gov/pubmed/32334946

Le Meur, Y., Morelon, E., Essig, M., Thierry, A., Büchler, M., Drouin, S., Deruelle, C., Badet, L., Pesteil, F., Delpech, P-O., Boutin, J-M., Renard, F., Barrou, B. First-in-human use of a marine oxygen carrier for organ preservation: a safety and proof-of-principle study. Am J Transplant. - 2020 https://www.ncbi.nlm.nih.gov/pubmed/32012441

Alix, P., Val-Laillet, D., Turlin, B., Ben Mosbah, I., Burel, A., Bobillier, E., Bendavid, C., Delpy, E., Zal, F., Corlu, A., Boudjema, K. Adding the oxygen carrier M101 to a cold-storage solution could be an alternative to HOPE for liver graft preservation. JHEP Rep. - 2020 https://pubmed.ncbi.nlm.nih.gov/32695967/

Lemaire, F., Sigrist, S., Delpy, E., Cherfan, J., Peronet, C., Zal, F., Bouzakri, K., Pinget, M., Maillard, E. Beneficial effects of the novel marine oxygen carrier M101 during cold preservation of rat and human pancreas. Journal of Cellular and Molecular Medicine. - 2019 https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14666

Kaminski, J., Hannaert, P., Kasil,A., Thuillier, R., Leize, E., Delpy, E., Steichen, C., Goujon, J.-M., Zal, F., Hauet, T. Efficacy of the natural oxygen transporter HEMO2life® in cold preservation in a preclinical porcine model of donation after cardiac death. Transplant International, official journal of the European Society for Organ Transplantation. - 2019 https://www.ncbi.nlm.nih.gov/pubmed/30924562

Thuillier, R., Delpy, E., Matillon, X., Kaminski J., Kasil, A., Soussi, D., Danion, J., Sauvageon, Y., Rod, X., Donatini, G., Barrou, B., Badet, L., Zal, F., Hauet, T. Preventing acute kidney injury during transplantation: the application of novel oxygen carriers. Expert Opinion on Investigational Drugs, 28(7):643-657. - 2019 https://www.ncbi.nlm.nih.gov/pubmed/31165652

Kasil, A., Giraud, S., Couturier, P., Amiri, A., Danion, J., Donatini, G., Matillon, X., Hauet, T., Badet, L. Individual and combined impact of oxygen and oxygen transporter supplementation during kidney machine preservation in a porcine preclinical kidney transplantation model. International Journal of Molecular Sciences, 20(8). - 2019 https://www.ncbi.nlm.nih.gov/pubmed/31018558

Glorion, M., Polard, V., Favereau, F., Hauet, T., Zal, F., Fadel, E., Sage, E. Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model. Artificial Cells, Nanomedicine, and Biotechnology, 46(8):1773-1780. - 2018 https://www.ncbi.nlm.nih.gov/pubmed/29069926

Ali, A., Watanabe, Y., Galasso, M., Stansfield, W., Watanabe, T., Ramandan, K., Chen, M., Ribeiro, R.P., Gokhale, H., Gazzalle, A., Waddell, T., Liu, M., Keshavjee, S., Cypel, M. Two-Day Lung Preservation Followed by Lung Transplantation in a Large Animal Model Using Novel Extracellular Oxygen Carrier. The Journal of Heart and Lung Transplantation, - 2018 https://www.jhltonline.org/article/S1053-2498(18)30296-1/abstract

Lemaire, F., Bietiger, W., Peronet, C., Langlois, A., Mura, C., Bouzakri, K., Sigrist, S., Polard, V., Zal, F., Pinget, M., and Maillard, E. Effect of HEMO2life®, a marine oxygen carrier, for pancreas preservation during cold ischemia. Poster presented during 8th international EPITA Symposium, Innsbruck, Austria. - 2018

Polard, V., Alix, P. Evaluation of a specific oxygen carrier (M101®) added to pig liver cold storage solutions to improve post-transplant graft function. Presented at the XVI ISBS, held November 13-15, 2017 in Montréal, Canada. - 2017

Teh, E. S., Zal, F., Polard, V., Menasché, P., Chambers, D.J. HEMO2life® as a protective additive to Celsior solution for static storage of donor hearts prior to transplantation. Artificial Cells, Nanomedicine, and Biotechnology, 45(4):717-722. - 2017 https://www.ncbi.nlm.nih.gov/pubmed/28079401

Mallet, V., Dutheil, D., Polard, V., Rousselot, M., Leize, E., Hauet, T., Goujon, J.-M., Zal, F. Dose-Ranging study of the performance of the natural oxygen transporter HEMO2life® in organ preservation. Artificials Organs, 38(8):691-701. - 2014 https://www.ncbi.nlm.nih.gov/pubmed/24749976

Zal, F., Rousselot, M. Extracellular Hemoglobins from Annelids, and their Potential Use in Biotechnology Outstanding Marine Molecules, Wiley‐VCH Verlag GmbH & Co. KGaA, - 2014 https://onlinelibrary.wiley.com/doi/abs/10.1002/9783527681501.ch16

Thuillier, R., Dutheil, D., Trieu, M.T.N., Mallet, V., Allain, G., Rousselot, M., Denizot, M., Goujon J.-M., Zal, F., Hauet, T. Supplementation with a new therapeutic oxygen carrier reduces chronic fibrosis and organ dysfunction in kidney static preservation. American Journal of Transplantation, 11(9):1845-1860. - 2011 https://www.ncbi.nlm.nih.gov/pubmed/21875432

Le Meur, Y., Delpy, E., Renard, F., Hauet, T., Badet, L., Rerolle, JP., Thierry, A., Büchler, M., Zal, F., Barrou, B. HEMO2life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study Artificial Organs. - 2021 https://pubmed.ncbi.nlm.nih.gov/34951495/

Latest press releases

Hemarina and Delpharm announce the signing of a partnership for the manufacture of HEMO2life®
November 29, 2018

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Brest University Hospital and HEMARINA present the new positive advances of the first clinical trial of HEMO2life® at the American Transplant Congress in Seattle,
June 6, 2018

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Hemarina and the University Health Network of Toronto announce positive preclinical proof of concept results for the HEMO2life® oxygen transporter in the preservation of lung transplants before transplantation
April 12, 2018

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Brest University Hospital and HEMARINA announce positive results from the first clinical trial of HEMO2life® in kidney conservation before transplantation in humans.
November 14, 2017

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