Key publications

Clinical Study Phase 2 – Marsyas II

Clinical Study Report – Synopsis
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Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer – study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II
Trials 22, 10 (2021). https://doi.org/10.1186/s13063-020-04948-1.
Gugerell A, Gouya-Lechner G, Hofbauer H, Laggner M, Trautinger F, Almer G, Peterbauer-Scherb A, Seibold M, Hoetzenecker W, Dreschl C, Mildner M, Ankersmit HJ.
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Clinical Study Phase 1 – Marsyas I

Study Report – Synopsis
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Zellüberstände apoptotischer, mononukleärer Zellen zur Wundheilung. Klinische Phase-I-Untersuchung beim Menschen
Simader E, Mildner M, Ankersmit HJ
Scriptum Dermatologie 4/2017
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Safety and tolerability of topically administered autologous, apoptotic PBMC secretome (APOSEC) in dermal wounds: a randomized Phase 1 trial (MARSYAS I)
Sci Rep. 2017 Jul 24;7(1):6216. doi: 10.1038/s41598-017-06223-x.
Simader E, Traxler D, Kasiri MM, Hofbauer H, Wolzt M, Glogner C, Storka A, Mildner M, Gouya G, Geusau A, Fuchs C, Eder C, Graf A, Schaden M, Golabi B, Aretin MB, Suessner S, Gabriel C, Klepetko W, Tschachler E, Ankersmit HJ.
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Publication featuring Aposec

New Therapies for the Treatment of Diabetic Foot Ulcers: Updated Review of Clinical Trials
Surg Technol Int. 2020 Nov 28;37:37-47.
Stratman S, Schneider C, Kirsner RS

Papers

Therapeutic Application of Cell Secretomes in Cutaneous Wound Healing. J Invest Dermatol. 2023 Jun;143(6):893-912. doi: 10.1016/j.jid.2023.02.019.
Bormann D, Gugerell A, Ankersmit HJ, Mildner M.
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The Secretome of Irradiated Peripheral Mononuclear Cells Attenuates Hypertrophic Skin Scarring
Pharmaceutics 2023, 15(4), 1065; https://doi.org/10.3390/pharmaceutics15041065
Vorstandlechner V, Copic D, Klas K, Direder M, Golabi B, Radtke C, Ankersmit HJ and Mildner M
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The Effect of Paracrine Factors Released by Irradiated Peripheral Blood Mononuclear Cells on Neutrophil Extracellular Trap Formation
Antioxidants 2022, 11(8), 1559; https://doi.org/10.3390/antiox11081559
Klas K,Ondracek AS,Hofbauer TM, Mangold A, Pfisterer K, Laggner M, Copic D, Direder M, Bormann D, Ankersmit HJ, Mildner M.
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Paracrine Factors of Stressed Peripheral Blood Mononuclear Cells Activate Proangiogenic and Anti-Proteolytic Processes in Whole Blood Cells and Protect the Endothelial Barrier
Pharmaceutics 2022, 14(8), 1600; https://doi.org/10.3390/pharmaceutics14081600
Copic D, Direder M, Schossleitner K, Laggner M, Klas K, Bormann D, Ankersmit HJ, Mildner M.
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The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils.
EBioMedicine. 2022 Jul;81:104093. doi: 10.1016/j.ebiom.2022.104093. Epub 2022 Jun 4.
Laggner M, Acosta GS, Kitzmüller C, Copic D, Gruber F, Altenburger LM, Vorstandlechner V, Gugerell A, Direder M, Klas K, Bormann D, Peterbauer A, Shibuya A, Bohle B, Ankersmit HJ, Mildner M.
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Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis.
Biology (Basel). 2022 Jan 13;11(1):116. doi: 10.3390/biology11010116.
Mildner CS, Copic D, Zimmermann M, Lichtenauer M, Direder M, Klas K, Bormann D, Gugerell A, Moser B, Hoetzenecker K, Beer L, Gyöngyösi M, Ankersmit HJ, Laggner M.
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Comparing the efficacy of γ- and electron-irradiation of PBMCs to promote secretion of paracrine, regenerative factors.
Molecuclar Therapy, Volume 21, P14-27, June 11, 2021.
Laggner M, Gugerell A, Copic D, Jeitler M, Springer M, Peterbauer A, Kremslehner C, Filzwieser-Narzt M, Gruber F, Madlener S, Erb M, Widder J, Lechner W, Georg D, Mildner M, Ankersmit HJ.
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TGF-β in the Secretome of Irradiated Peripheral Blood Mononuclear Cells Supports In Vitro Osteoclastogenesis.
Int. J. Mol. Sci. 2020, 21(22), 8569; doi:10.3390/ijms21228569.
Panahipour L, Kargarpour Z, Laggner M, Mildner M, Ankersmit HJ, Gruber R.
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The secretome of stressed peripheral blood mononuclear cells increases tissue survival in a rodent epigastric flap model.
Bioeng Transl Med. 2020;e10186. doi: 10.1002/btm2.10186.
Hacker S, Mittermayr R, Traxler D, Keibl C, Resch A, Salminger S, Leiss H, Hacker P, Gabriel C, Golabi B, Pauzenberger R, Slezak P, Laggner M, Mildner M, Michlits W, Ankersmit HJ.
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Role for Lipids Secreted by Irradiated Peripheral Blood Mononuclear Cells in Inflammatory Resolution in Vitro.
International Journal of Molecular Sciences 2020, 21, 4694; doi:10.3390/ijms21134694.
Panahipour L, Kochergina E, Laggner M, Zimmermann M, Mildner M, Ankersmit HJ, Gruber R.
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Quantitative Hybrid Cardiac [18F]FDG-PET-MRI Images for Assessment of Cardiac Repair by Preconditioned Cardiosphere-Derived Cells.
Molecular Therapy. Methods & Clinical Development. Vol. 18, 11 Sept 2020, p 354-366. doi: 10.1016/j.omtm.2020.06.008.
Winkler J, Lukovic D, Mester-Tonczar J, Zlabinger K, Gugerell A, Pavo N, Jakab A. Szanka Z, Traxler1 D, Müller C, Spannbauer A, Riesenhuber M, Hasimbegovic E, Dawkins J, Zimmermann M, Ankersmit HJ, Marban E, Gyöngyösi M.
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Therapeutic potential of lipids obtained from γ-irradiated PBMCs in dendritic cell-mediated skin inflammation.
EBioMedicine. 2020 May;55:102774. doi: 10.1016/j.ebiom.2020.102774. Epub 2020 May 8.
Laggner M, Copic D, Nemec L, Vorstandlechner V, Gugerell A, Gruber F, Peterbauer A, Ankersmit HJ, Mildner M.
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Reproducibility of GMP-compliant production of therapeutic stressed peripheral blood mononuclear cell-derived secretomes, a novel class of biological medicinal products.
Stem Cell Res Ther. 2020 Jan 3;11(1):9. doi: 10.1186/s13287-019-1524-2.
Laggner M, Gugerell A, Bachmann C, Hofbauer H, Vorstandlechner V, Seibold M, Gouya Lechner G, Peterbauer A, Madlener S, Demyanets S, Sorgenfrey D, Ostler T, Erb M, Mildner M, Ankersmit HJ.
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Tissue-regenerative potential of the secretome of γ-irradiated peripheral blood mononuclear cells is mediated via TNFRSF1B-induced necroptosis
Cell Death Dis. 2019 Sep 30;10(10):729. doi: 10.1038/s41419-019-1974-6.
Simader E, Beer L, Laggner M, Vorstandlechner V2, Gugerell A, Erb M, Kalinina P, Copic D, Moser D, Spittler A, Tschachler E, Jan Ankersmit H, Mildner M
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Viral safety of APOSEC™: a novel peripheral blood mononuclear cell derived-biological for regenerative medicine
Blood Transfus. 2019 Feb 21. doi: 10.2450/2019.0249-18.
Gugerell A, Sorgenfrey D, Laggner M, Raimann J, Peterbauer A, Bormann D, Suessner S, Gabriel C, Moser B, Ostler T, Mildner M, Ankersmit HJ
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Toxicological testing of allogeneic secretome derived from peripheral mononuclear cells (APOSEC): a novel cell-free therapeutic agent in skin disease
Sci Rep. 2019 Apr 3;9(1):5598. doi: 10.1038/s41598-019-42057-5.
Wuschko S, Gugerell A, Chabicovsky M, Hofbauer H, Laggner M, Erb M, Ostler T, Peterbauer A, Suessner S, Demyanets S, Leuschner J, Moser B, Mildner M, Ankersmit HJ
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Different pro-angiogenic potential of γ-irradiated PBMC-derived secretome and its subfractions
Sci Rep. 2018 Dec 20;8(1):18016. doi: 10.1038/s41598-018-36928-6.
Wagner T, Traxler D, Simader E, Beer L, Narzt MS, Gruber F, Madlener S, Laggner M, Erb M, Vorstandlechner V, Gugerell A, Radtke C, Gnecchi M, Peterbauer A, Gschwandtner M, Tschachler E, Keibl C, Slezak P, Ankersmit HJ, Mildner M
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Ionizing radiation regulates long non-coding RNAs in human peripheral blood mononuclear cells
J Radiat Res. 2017 Mar 1;58(2):201-209. doi: 10.1093/jrr/rrw111.
Beer L, Nemec L, Wagner T, Ristl R, Altenburger LM, Ankersmit HJ, Mildner M
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Cell secretome based drug substances in regenerative medicine: when regulatory affairs meet basic science
Ann Transl Med. . 2017 Apr;5(7):170. doi: 10.21037/atm.2017.03.50.
Beer L, Mildner M, Ankersmit HJ
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Peripheral blood mononuclear cell secretome for tissue repair
Apoptosis. 2016 Dec;21(12):1336-1353. doi: 10.1007/s10495-016-1292-8.
Beer L, Mildner M, Gyöngyösi M, Ankersmit HJ
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Dying blood mononuclear cell secretome exerts antimicrobial activity
Eur J Clin Invest. 2016 Oct;46(10):853-63. doi: 10.1111/eci.12667. Epub 2016 Sep 26.
Kasiri MM, Beer L, Nemec L, Gruber F, Pietkiewicz S, Haider T, Simader EM, Traxler D, Schweiger T, Janik S, Taghavi S, Gabriel C, Mildner M, Ankersmit HJ
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Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model
Sci Rep. 2016 Apr 29;6:25168. doi: 10.1038/srep25168.
Hacker S, Mittermayr R, Nickl S, Haider T, Lebherz-Eichinger D, Beer L, Mitterbauer A, Leiss H, Zimmermann M, Schweiger T, Keibl C, Hofbauer H, Gabriel C, Pavone-Gyöngyösi M, Redl H, Tschachler E, Mildner M, Ankersmit HJ
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Analysis of the secretome of apoptotic peripheral blood mononuclear cells: impact of released proteins and exosomes for tissue regeneration
Sci Rep. 2015 Nov 16;5:16662. doi: 10.1038/srep16662.
Beer L, Zimmermann M, Mitterbauer A, Ellinger A, Gruber F, Narzt M-S, Zellner M, Gyöngyösi M, Madlener S, Simader E; Gabriel C, Mildner M, Ankersmit HJ
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The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats
Exp Neurol. 2015 Mar 19. pii: S0014-4886(15)00081-3. doi: 10.1016/j.expneurol.2015.03.013. [Epub ahead of print]
Haider T, Höftberger R, Rüger B, Mildner M, Blumer R, Mitterbauer A, Buchacher T, Sherif C, Redl H, Gabriel C, Gyöngyösi M, Fischer MB, Lubec G, Ankersmit HJ
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High dose ionizing radiation regulates micro RNA and gene expression changes in human peripheral blood mononuclear cells
BMC Genomics. 2014 Sep 25;15:814; doi: 10.1186/1471-2164-15-814
Beer L, Seemann R, Ristl R, Ellinger A, Kasiri MM, Mitterbauer A, Zimmermann M, Gabriel C, Gyöngyösi M, Klepetko W, Mildner M1, Ankersmit HJ
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Secretomes of Apoptotic Mononuclear Cells Ameliorate Neurological Damage in Rats with Focal Ischemia
F1000 Research 2014, 3:131
Altmann P, Mildner M, Haider T, Traxler D, Beer L, Ristl R, Golabi B, Gabriel C, Leutmetzer F, Ankersmit HJ
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Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine ischemic left ventricular dysfunction
Biomaterials. 2014 Apr;35(11):3541-50. doi: 10.1016/j.biomaterials.2013.12.071. Epub 2014 Jan 16.
Pavo N, Zimmermann N, Mildner M, Petrási Z, Petneházy O, Fuzik J, Jakab A, Gabriel C, Sipos W, Maurer G, Gyöngyösi M, Ankersmit HJ
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Secretome of Peripheral Blood Mononuclear Cells Enhances Wound Healing
PLOS ONE, 22 March 2013, 10.1371/journal.pone.0060103
Mildner M, Hacker S, Haider T, Gschwandtner M, Werba G, Barresi C, Zimmermann M, Golabi B, Tschachler E, Ankersmit HJ
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Mononuclear cell secretome protects from experimental autoimmune myocarditis
European Heart Journal. 2013 Jan; doi:10.1093/eurheartj/ehs459 (Advance Access)
Hoetzenecker K, Zimmermann M, Hoetzenecker W, Schweiger T, Kollmann D, Mildner M, Hegedus B, Mitterbauer A, Hacker S, Birner P, Gabriel C, Gyöngyösi M, Blyszczuk P, Eriksson U, Ankersmit HJ
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Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction
Basic Research Cardiology 2011 Jun;106(4):645-55
Lichtenauer M, Mildner M, Baumgartner A, Hasun M, Werba G, Beer L, Altmann P, Roth G, Gyöngyösi M, Podesser BK, and Ankersmit HJ
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Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study
Basic Res Cardiol. 2011 Nov;106(6):1283-97
Lichtenauer M, Mildner M, Hoetzenecker K, Zimmermann M, Podesser BK, Sipos W, Berényi E, Dworschak M, Tschachler E, Gyöngyösi M, Ankersmit HJ
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Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation
Basic Res Cardiol. 2012 Sep;107(5):292. Epub 2012 Aug 17
Hoetzenecker K, Assinger A, Lichtenauer M, Mildner M, Schweiger T, Starlinger P, Jakab A, Berényi E, Pavo N, Zimmermann M, Gabriel C, Plass C, Gyöngyösi M, Volf I, Ankersmit HJ
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Apoptotische Leukozyten und deren Sekretionsprodukt. Relevanz für die Herzinfarkttherapie beim Menschen
Wiener klinisches Magazin 5/2011
Lichtenauer M, Mildner M, Gyöngyösi M, Ankersmit HJ
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Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium
Eur J Clin Invest. 2009 Jun;39(6):445-56. Epub 2009 Apr 16
Ankersmit HJ, Hoetzenecker K, Dietl W, Soleiman A, Horvat R, Wolfsberger M, Gerner C, Hacker S, Mildner M, Moser B, Lichtenauer M, Podesser BK
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PhD-Theses

Regenerative potential of the secretome of apoptotic and necroptotic peripheral blood mononuclear cells from bench to clinical phase I trial in dermal wounds
Elisabeth Simader (2024)

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Peripheral blood mononuclear cell-secretome attenuates fibrotic effects in wound healing and scar formation
Vera Vorstandlechner (2024)

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Paracrine factors released by γ-irradiated peripheral blood mononuclear cells inhibit neutrophil extracellular trap formation
Katharina Klas (2023)

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Antimicrobial Defence in Human Body Fluids – High Antimicrobial Peptide Expression in Postoperative Pleural Fluid and Stressed Mononuclear cells
Mohammad Mahdi Kasiri (2020)

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Cardiac regeneration in ischaemic cardiomyopathy
Cell-free cardiac regeneration in ischaemic cardiomyopathy: The paracrine regenerative effect of the secretome of apoptotic peripheral blood mononuclear cells (APOSEC)
Noemi Pavo (2016)

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Therapeutic Capacity of Apoptotic Mononuclear Cell Secretome in Experimental Spinal Cord Injury
Thomas Haider (2016)

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The effects of high dose ionizing radiation on transcriptional regulation and paracrine signaling inhuman peripheral blood mononuclear cells
Lucian Beer (2015)

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The secretome of mononuclear cells as a therapeutic tool in myocardial infarction and myocarditis: an experimental study
Konrad Hoetzenecker (2012)

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Secretome of apoptotic cells causes cardioprotection and inhibits ventricular remodeling after acute myocardial infarction
Michael Lichtenauer (2011)

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