The use of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis: a pre-clinical study

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Salmenkari, HannePharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (author)

The use of unlicensed bone marrow-derived platelet lysate-expanded mesenchymal stromal cells in colitis : a pre-clinical study

Article/chapterEnglish2019

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Elsevier,2019
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LIBRIS-ID:oai:DiVA.org:oru-83104
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-83104URI
https://doi.org/10.1016/j.jcyt.2018.11.011DOI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Funding Agencies:Finnish Funding Agency for Technology & Innovation (TEKES) 3982/31/2013Juhani Aho Medical Research Foundation, Finland Finska Läkaresällskapet Einar och Karin Stroems Stiftelse, Finland
Background: Mesenchymal stromal cells (MSCs) are a promising candidate for treatment of inflammatory disorders, but their efficacy in human inflammatory bowel diseases (IBDs) has been inconsistent. Comparing the results from various preclinical and clinical IBD studies is also challenging due to a large variation in study designs.Methods: In this comparative pre-clinical study, we compared two administration routes and investigated the safety and feasibility of both fresh and cryo-preserved platelet-lysate-expanded human bone marrow-derived MSCs without additional licensing in a dextran sodium sulfate (DSS) colitis mouse model both in the acute and regenerative phases of colitis. Body weight, macroscopic score for inflammation and colonic interleukin (IL)-1 beta and tumor necrosis factor (TNF)alpha concentrations were determined in both phases of colitis. Additionally, histopathology was assessed and Il-1 beta and Agtr1a messenger RNA (mRNA) levels and angiotensin-converting enzyme (ACE) protein levels were measured in the colon in the regenerative phase of colitis.Results: Intravenously administered MSCs exhibited modest anti-inflammatory capacity in the acute phase of colitis by reducing IL-1 beta protein levels in the inflamed colon. There were no clear improvements in mice treated with fresh or cryopreserved unlicensed MSCs according to weight monitoring results, histopathology and macroscopic score results. Pro-inflammatory ACE protein expression and shedding were reduced by cryopreserved MSCs in the colon.Conclusions: In conclusion, we observed a good safety profile for bone marrow-derived platelet lysate-expanded MSCs in a mouse pre-clinical colitis model, but the therapeutic effect of MSCs prepared without additional licensing (i.e. such as MSCs are administered in graft-versus-host disease) was modest in the chosen in vivo model system and limited to biochemical improvements in cytokines without a clear benefit in histopathology or body weight development.

Subject headings and genre

NATURVETENSKAP Biologi Cellbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Cell Biology hsv//eng
cryopreservation
dextran sodium sulfate colitis
licensing
mesenchymal stromal cells
renin-angiotensin system

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Laitinen, AnitaAdvanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland (author)
Forsgård, Richard A.,1987-Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland(Swepub:oru)rfd (author)
Holappa, MerviPharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (author)
Linden, JereDepartment of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland (author)
Pasanen, LauriPharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (author)
Korhonen, MattiAdvanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland (author)
Korpela, RiittaPharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland (author)
Nystedt, JohannaAdvanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland (author)
Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, FinlandAdvanced Cell Therapy Centre, Finnish Red Cross Blood Service, Helsinki, Finland (creator_code:org_t)

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In:Cytotherapy: Elsevier21:2, s. 175-1881465-32491477-2566

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By the author/editor: Salmenkari, Hann ...; Laitinen, Anita; Forsgård, Richar ...; Holappa, Mervi; Linden, Jere; Pasanen, Lauri; show more...; Korhonen, Matti; Korpela, Riitta; Nystedt, Johanna; show less...

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