Z Gastroenterol 2018; 56(08): e251-e252
DOI: 10.1055/s-0038-1668789
Kurzvorträge
Leber und Galle
Leber: Fibrose, Steatose, Speicherkrankheiten – Donnerstag, 13. September 2018, 09:50 – 11:18, 22a
Georg Thieme Verlag KG Stuttgart · New York

Human skin-derived ABCB5+ mesenchymal stem cell injection improves liver disease parameters in Mdr2ko mice

V Hartwig
1   Universität Heidelberg, Medizinische Fakultät Mannheim, Molekulare Hepatologie, II. Medizinische Klinik, Mannheim, Deutschland
,
T Lin
1   Universität Heidelberg, Medizinische Fakultät Mannheim, Molekulare Hepatologie, II. Medizinische Klinik, Mannheim, Deutschland
,
B Dewidar
1   Universität Heidelberg, Medizinische Fakultät Mannheim, Molekulare Hepatologie, II. Medizinische Klinik, Mannheim, Deutschland
,
A Kluth
2   Rheacell GmbH, Heidelberg, Deutschland
,
N Tappenbeck
2   Rheacell GmbH, Heidelberg, Deutschland
,
B Christ
3   Universität Leipzig, Klinik und Poliklinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Molekulare Hepatologie, Leipzig, Deutschland
,
A Dropmann
1   Universität Heidelberg, Medizinische Fakultät Mannheim, Molekulare Hepatologie, II. Medizinische Klinik, Mannheim, Deutschland
,
S Dooley
1   Universität Heidelberg, Medizinische Fakultät Mannheim, Molekulare Hepatologie, II. Medizinische Klinik, Mannheim, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
13 August 2018 (online)

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Introduction:

ABCB5+ cells are mesenchymal stem cells isolated from human skin (sMSC). A therapeutic potential was shown in chronic venous ulcers.

Aim:

Because of organ-donor limitations, we suggest that sMSC provide a promising therapy option for patients with chronic/end stage liver disease, where is no other option for survival than liver transplantation.

Methods:

16 weeks old Mdr2ko mice, exerting inflammation-related fibrosis, were tail vein injected with 5 × 105 ABCB5+ cells. After 2 days, 6 days, 2 and 4 weeks liver damage parameters were evaluated on mRNA and protein levels.

To get insight on cellular effects, cultured human hepatic stellate cells, LX-2, were treated with supernatant of sMSC with or without previous macrophage stimulation, and activation parameters were investigated.

Results:

Application of sMSC to Mdr2ko mice did not implicate body and liver weight changes nor increase liver plasma parameters (ALT, AST, AP), indicating lack of toxicity. A significant reduction of fibrosis was seen in ABCB5+ treated Mdr2ko mice by quantifying Picro Sirius Red positive staining. This is, however, not reflected at the mRNA level, where typical fibrosis markers like Timp1, aSMA, TGF-b, Col1A1 or CTGF are not significantly changed. We further observe a significant increase of infiltrating Kupffer cell numbers in stem cell treated mice, as evidenced by F4/80 and CD163 staining, without significant changes at mRNA levels for TNFa and IL-6, whereas IL-1b and anti-inflammatory IL-10 are increased. Finally, sMSC injected mice display increased proliferative activity in hepatocytes and non-parenchymal cells, as evident from Ki67 staining. In vitro, sMSC supernatant increases aSMA expression and TGF-b signalling of LX-2 cells, whereby Vimentin expression is significantly decreased.

Conclusions:

Mdr2ko mice tolerated sMSC application very well and a significant reduction of collagen deposition is a promising preliminary result. An increasing number of proliferating cells further indicate improved regenerative activity. One important factor secreted from sMSC is obviously TGF-b.