M2RLab is currently working in the development of therapies treating life threatening diseases, such as acute renal failure (ARF) and acute respiratory distress syndrome (ARDS), and invalidating injuries with very high incidence in tendon and muscle.

ACUTE RENAL FAILURE

Acute renal failure (ARF) affects more than 1 million people a year in Europe, Japan and the United States and involves inflammatory processes in the kidney that can lead to complete loss of kidney function. It is estimated that 12% of patients who have suffered acute renal failure require subsequent dialysis treatment. It is estimated that in 5 years it will be the 5th cause of death. There are still no therapies that allow treating ARF in its early stages, so the development of new therapeutic alternatives is of great interest.

MUSCULAR INJURY

Although muscular tissue has the ability to regenerate, in severe injuries this process is delayed and a total restitution is not achieved, forming scar tissue. Scar tissue reduces patient motility and makes them more prone to reinjury. The initial inflammatory and reparative process generate a fibrotic response that could be avoided inhibiting the initial inflammation and changing the inflammatory environment in order to balance the regeneration process avoiding fibrosis.

ARDS

The most common complication in COVID 19 patients is the acute respiratory distress syndrome (ARDS) which is caused by the release of inflammatory compounds that reduce lung function. Approximately 14% of COVID-19 patients develop a serious illness that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. ARDS is a common complication not only for COVID patients, but also on other pathogen infections, and remains a largely unmet medical need.

OUR RESEACH TEAM PUBLISHED ARTICLES

Macrophage Phenotype and Fibrosis in Diabetic Nephropathy.

Calle P,Hotter G.Int J Mol Sci. 2020 Apr 17;21(8):2806. doi: 10.3390/ijms21082806.PMID: 32316547 Free PMC article.Review.

 

Urinary Neuropilin-1: A Predictive Biomarker for Renal Outcome in Lupus Nephritis.

Torres-Salido MT, Sanchis M, Solé C, Moliné T, Vidal M, Vidal X, Solà A, Hotter G, Ordi-Ros J, Cortés-Hernández J.Int J Mol Sci. 2019 Sep 17;20(18):4601. doi: 10.3390/ijms20184601.PMID: 31533337 Free PMC article.

 

CPT1a gene expression reverses the inflammatory and anti-phagocytic effect of 7-ketocholesterol in RAW264.7 macrophages.

Calle P, Muñoz A, Sola A,Hotter G.Lipids Health Dis. 2019 Dec 10;18(1):215. doi: 10.1186/s12944-019-1156-7.PMID: 31823799 Free PMC article.

 

CPT1a downregulation protects against cholesterol-induced fibrosis in tubular epithelial cells by downregulating TGFβ-1 and inflammasome.

Calle P, Torrico S, Muñoz A, Hotter G. Biochem Biophys Res Commun. 2019 Oct 1;517(4):715-721. doi: 10.1016/j.bbrc.2019.07.121. Epub 2019 Aug 9.PMID: 31405564 Free article.

 

Exploring macrophage cell therapy on Diabetic Kidney Disease.

Guiteras R, Sola A, Flaquer M, Manonelles A, Hotter G, Cruzado JM.J Cell Mol Med. 2019 Feb;23(2):841-851. doi: 10.1111/jcmm.13983. Epub 2018 Nov 8.PMID: 30407737 Free PMC article.

 

The influenza virus NS1A binding protein gene modulates macrophages response to cytokines and phagocytic potential in inflammation.

Hotter G, Mastora C, Jung M, Brüne B, Carbonell T, Josa C, Pérez-Calvo JI, Cruzado JM, Guiteras R, Sola A.Sci Rep. 2020 Sep 17;10(1):15302. doi: 10.1038/s41598-020-72342-7.PMID: 32943673 Free PMC article.

Lipocalin-2 abrogates epithelial cell cycle arrest by PPARγinhibition.

Jung M, Brüne B, von Knethen A, Guiteras R, Cruzado JM, Hotter G, Sola A. Lab Invest. 2018 Nov;98(11):1408-1422. doi: 10.1038/s41374-018-0098-4. Epub 2018 Aug 7.PMID: 30087458

 

Microencapsulated macrophages releases conditioned medium able to prevent epithelial to mesenchymal transition.

Sola A, Saenz Del Burgo L, Ciriza J, Hernandez RM, Orive G, Martin Cordero J, Calle P, Pedraz JL, Hotter G. Drug Deliv. 2018 Nov;25(1):91-101. doi: 10.1080/10717544.2017.1413449.PMID: 29250977 Free PMC article.

 

Macrophage Overexpressing NGAL Ameliorated Kidney Fibrosis in the UUO Mice Model.

Guiteras R, Sola A, Flaquer M, Hotter G, Torras J, Grinyó JM, Cruzado JM. Cell Physiol Biochem. 2017;42(5):1945-1960. doi: 10.1159/000479835. Epub 2017 Aug 9.PMID: 28793288

 

Carbonic Anhydrase Protects Fatty Liver Grafts against Ischemic Reperfusion Damage.

Bejaoui M, Pantazi E, De Luca V, Panisello A, Folch-Puy E, Hotter G, Capasso C, T Supuran C, Roselló-Catafau J. PLoS One. 2015 Jul 30;10(7):e0134499. doi: 10.1371/journal.pone.0134499. eCollection 2015.PMID: 26225852 Free PMC article.

 

Macrophage-derived Lipocalin-2 contributes to ischemic resistance mechanisms by protecting from renal injury.

Jung M, Brüne B, Hotter G,Sola A. Sci Rep. 2016 Feb 25;6:21950. doi: 10.1038/srep21950.PMID: 26911537 Free PMC article.

 

Lipocalin-2-induced renal regeneration depends on cytokines.

Vinuesa E, Sola A, Jung M, Alfaro V, Hotter G. Am J Physiol Renal Physiol. 2008 Nov;295(5):F1554-62. doi: 10.1152/ajprenal.90250.2008. Epub 2008 Sep 24.PMID: 18815220

miRNA let-7e targeting MMP9 is involved in adipose-derived stem cell differentiation toward epithelia.

Ventayol M, Viñas JL, Sola A, Jung M, Brüne B, Pi F, Mastora C, Hotter G. Cell Death Dis. 2014 Feb 6;5(2):e1048. doi: 10.1038/cddis.2014.2.PMID: 24503540 Free PMC article.

 

miRNA let-7e modulates the Wnt pathway and early nephrogenic markers in mouse embryonic stem cell differentiation.

Viñas JL, Ventayol M, Brüne B, Jung M, Sola A, Pi F, Mastora C, Hotter G. PLoS One. 2013 Apr 10;8(4):e60937. doi: 10.1371/journal.pone.0060937. Print 2013.PMID: 23593353 Free PMC article.

 

Interleukin-10-induced neutrophil gelatinase-associated lipocalin production in macrophages with consequences for tumor growth.

Jung M, Weigert A, Tausendschön M, Mora J, Ören B, Sola A, Hotter G, Muta T, Brüne B.Mol Cell Biol. 2012 Oct;32(19):3938-48. doi: 10.1128/MCB.00413-12. Epub 2012 Jul 30.PMID: 22851691 Free PMC article.

 

Infusion of IL-10-expressing cells protects against renal ischemia through induction of lipocalin-2.

Jung M, Sola A, Hughes J, Kluth DC, Vinuesa E, Viñas JL, Pérez-Ladaga A, Hotter G. Kidney Int. 2012 May;81(10):969-982. doi: 10.1038/ki.2011.446. Epub 2012 Jan 25.PMID: 22278021

 

Sphingosine-1-phosphate signalling induces the production of Lcn-2 by macrophages to promote kidney regeneration.

Sola A, Weigert A, Jung M, Vinuesa E, Brecht K, Weis N, Brüne B, Borregaard N, Hotter G. J Pathol. 2011 Dec;225(4):597-608. doi: 10.1002/path.2982.PMID: 22025214

 

Actin cytoskeleton derangement induces apoptosis in renal ischemia/reperfusion.

Genescà M, Sola A, Hotter G. Apoptosis. 2006 Apr;11(4):563-71. doi: 10.1007/s10495-006-4937-1.PMID: 16528472