Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines

Guido Moll; James A Ankrum; Julian Kamhieh-Milz; Karen Bieback; Olle Ringdén; Hans-Dieter Volk; Sven Geissler; Petra Reinke

doi:10.1016/j.molmed.2018.12.006

Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines

Trends Mol Med. 2019 Feb;25(2):149-163. doi: 10.1016/j.molmed.2018.12.006. Epub 2019 Jan 30.

Authors

Guido Moll¹, James A Ankrum², Julian Kamhieh-Milz³, Karen Bieback⁴, Olle Ringdén⁵, Hans-Dieter Volk⁶, Sven Geissler⁷, Petra Reinke⁸

Affiliations

¹ Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Berlin-Brandenburg School for Regenerative Therapies (BSRT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany. Electronic address: guido.moll@charite.de.
² Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA; Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA.
³ Department of Transfusion Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany.
⁴ Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; German Red Cross Blood Donor Service Baden-Württemberg-Hessen, Mannheim, Germany.
⁵ Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
⁶ Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Institute of Medical Immunology, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Berlin Center for Advanced Therapies (BECAT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Equal contribution senior authorship.
⁷ Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Julius Wolff Institute (JWI), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Equal contribution senior authorship.
⁸ Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Department of Nephrology and Internal Intensive Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Berlin Center for Advanced Therapies (BECAT), Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin (FUB), Humboldt-Universität zu Berlin (HUB), and Berlin Institute of Health (BIH), Berlin, Germany; Equal contribution senior authorship.

PMID: 30711482
DOI: 10.1016/j.molmed.2018.12.006

Abstract

Intravascular infusion is the most popular route for therapeutic multipotent mesenchymal stromal/stem cell (MSC) delivery in hundreds of clinical trials. Meta-analysis has demonstrated that bone marrow MSC infusion is safe. It is not clear if this also applies to diverse new cell products derived from other sources, such as adipose and perinatal tissues. Different MSC products display varying levels of highly procoagulant tissue factor (TF) and may adversely trigger the instant blood-mediated inflammatory reaction (IBMIR). Suitable strategies for assessing and controlling hemocompatibility and optimized cell delivery are crucial for the development of safer and more effective MSC therapies.

Keywords: CD142; cellular therapy; hemocompatibility; mesenchymal stromal/stem cell; safety and efficacy; tissue factor; tissue source.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Clinical Trials as Topic
Humans
Inflammation / etiology
Inflammation / immunology
Mesenchymal Stem Cell Transplantation / adverse effects
Mesenchymal Stem Cell Transplantation / methods*
Mesenchymal Stem Cells / cytology*
Mesenchymal Stem Cells / immunology
Thromboplastin / analysis
Thromboplastin / immunology

Substances

Thromboplastin