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

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

Journal article

Open access

Peer reviewed

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 and Petra Reinke

Trends in molecular medicine, Vol.25(2), pp.149-163

02/2019

DOI: 10.1016/j.molmed.2018.12.006

PMID: 30711482

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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. MSC products have largely diversified during the past decade, making extrapolation about safety and efficacy from first-generation products inappropriate. MSCs and other blood non-resident cellular therapeutics display different degrees of incompatibility with human blood, which compromises their safety and efficacy. TF is the major determinant of cell product hemocompatibility, and this should be routinely monitored in all therapeutics intended for intravascular delivery. MSC products from different tissue sources display high variability in TF expression, with potential lethal consequences for patients when infused systemically. Once aware of the problem, a large array of product and process innovations became available to improve the clinical delivery of systemically infused cellular therapeutics.

CD142

hemocompatibility

tissue factor

safety and efficacy

cellular therapy

mesenchymal stromal/stem cell

tissue source

Details

Title: Subtitle: Intravascular Mesenchymal Stromal/Stem Cell Therapy Product Diversification: Time for New Clinical Guidelines
Creators: Guido Moll - 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
James A Ankrum - Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, IA, USA
Julian Kamhieh-Milz - 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
Karen Bieback - Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Olle Ringdén - Translational Cell Therapy Research (TCR), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden
Hans-Dieter Volk - 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
Sven Geissler - 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
Petra Reinke - 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
Resource Type: Journal article
Publication Details: Trends in molecular medicine, Vol.25(2), pp.149-163
DOI: 10.1016/j.molmed.2018.12.006
PMID: 30711482
NLM abbreviation: Trends Mol Med
ISSN: 1471-4914
eISSN: 1471-499X
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/501100001659, name: German Research Foundation; name: German Federal Ministry of Education and Research, award: GSC203; name: BMBF, award: 01EC1402B; name: DFG, award: FOR2165, GE2512/2-2; name: EU Horizon 2020, award: 733006, 779293; DOI: 10.13039/100002069, name: Fraternal Order of Eagles; DOI: 10.13039/501100004359, name: Swedish Research Council, award: K2014-64X-05971-34-4; DOI: 10.13039/501100002794, name: Swedish Cancer Society, award: CAN2013/671; DOI: 10.13039/501100007231, name: Cancer Society in Stockholm, award: 111293; DOI: 10.13039/501100004047, name: Karolinska Institutet
Language: English
Date published: 02/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering
Record Identifier: 9984000923202771

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