In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials
| العنوان: | In vivo safety profile and biodistribution of GMP-manufactured human skin-derived ABCB5-positive mesenchymal stromal cells for use in clinical trials |
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| المؤلفون: | Kathrin Dieter, Christoph Ganss, Markus H. Frank, George F. Murphy, Karin Scharffetter-Kochanek, Korinna Kraft, Elke Niebergall-Roth, Natasha Y. Frank, Ulf Dehio, Andreas Kerstan, Nils Tappenbeck, Mark A. Kluth, Fathema Hassinger, Jasmina Esterlechner, Joachim Beck, Hannes M. Schröder, Dennis P. Orgill |
| المصدر: | Cytotherapy |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, safety, Male, Quality Control, Cancer Research, Biodistribution, Stromal cell, ATP Binding Cassette Transporter, Subfamily B, Immunology, Pharmacology, Mesenchymal Stem Cell Transplantation, Regenerative medicine, Injections, Intramuscular, Article, Cell therapy, MSC, 03 medical and health sciences, 0302 clinical medicine, In vivo, stem cells, Mice, Inbred NOD, Immunology and Allergy, Medicine, Animals, Humans, Tissue Distribution, biodistribution, Genetics (clinical), stromal cells, Skin, Transplantation, business.industry, GMP, Mesenchymal stem cell, toxicity, Cell Differentiation, Mesenchymal Stem Cells, Cell Biology, persistence, ABCB5, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, tumorigenicity, Administration, Intravenous, Female, Stem cell, business, Intramuscular injection |
| الوصف: | Background aims Human dermal ABCB5-expressing mesenchymal stromal cells (ABCB5+ MSCs) represent a promising candidate for stem cell–based therapy of various currently uncurable diseases in several fields of regenerative medicine. We have developed and validated a method to isolate, from human skin samples, and expand ABCB5+ MSCs that meet the guideline criteria of the International Society for Cellular Therapy. We are able to process these cells into a Good Manufacturing Practice–conforming, MSC-based advanced-therapy medicinal product. Methods To support the development of ABCB5+ MSCs for potential therapeutic topical, intramuscular and intravenous administration, we have tested our product in a series of Good Laboratory Practice–compliant nonclinical in-vivo studies addressing all relevant aspects of biosafety, including potential long-term persistence and proliferation, distribution to nontarget tissues, differentiation into undesired cell types, ectopic tissue formation, tumor formation and local tissue reaction. Results (i) Subcutaneous application of 1 × 107 ABCB5+ MSCs/animal and intravenous application of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice did not result in safety-relevant biodistribution, persistence or proliferation of the cells; (ii) three monthly subcutaneous injections of ABCB5+ MSCs at doses ranging from 1 × 105 to 1 × 107 cells/animal and three biweekly intravenous injections of 2 × 106 ABCB5+ MSCs/animal, respectively, to immunocompromised mice were nontoxic and revealed no tumorigenic potential; and (iii) intramuscular injection of 5 × 106 ABCB5+ MSCs/animal to immunocompromised mice was locally well tolerated. Discussion The present preclinical in vivo data demonstrate the local and systemic safety and tolerability of a novel advanced-therapy medicinal product based on human skin-derived ABCB5+ MSCs. |
| اللغة: | English |
| تدمد: | 1477-2566 1465-3249 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce756877bed07b371ecef609532200f7 http://europepmc.org/articles/PMC6513723 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ce756877bed07b371ecef609532200f7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14772566 14653249 |
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