Journalartikel

Jahr der Veröffentlichung: 2020

Zeitschrift: Stem Cell Research and Therapy

Bandnummer: 11

Heftnummer: 1

eISSN: 1757-6512

Open Access Status: Gold

DOI Link: https://doi.org/10.1186/s13287-020-02007-9

Verlag: BioMed Central

Abstract: 
BackgroundMesenchymal stem cells (MSC) are non-haematopoietic, fibroblast-like multipotent stromal cells. In the injured pancreas, these cells are assumed to secrete growth factors and immunomodulatory molecules, which facilitate the regeneration of pre-existing beta -cells. However, when MSC are delivered intravenously, their majority is entrapped in the lungs and does not reach the pancreas. Therefore, the aim of this investigation was to compare the regenerative support of hTERT-MSC (human telomerase reverse transcriptase mesenchymal stem cells) via intrapancreatic (IPR) and intravenous route (IVR).MethodshTERT-MSC were administered by IPR and IVR to 50% pancreatectomized NMRI nude mice. After eight days, blood glucose level, body weight, and residual pancreatic weight were measured. Proliferating pancreatic beta -cells were labelled and identified with bromodeoxyuridine (BrdU) in vivo. The number of residual islets and the frequency of proliferating beta -cells were compared in different groups with sequential pancreatic sections. The pancreatic insulin content was evaluated by enzyme-linked immunosorbent assay (ELISA) and the presence of hTERT-MSC with human Alu sequence. Murine gene expression of growth factors, beta -cell specific molecules and proinflammatory cytokines were inspected by real-time polymerase chain reaction (RT-PCR) and Western blot.ResultsThis study evaluated the regenerative potential of the murine pancreas post-hTERT-MSC administration through the intrapancreatic (IPR) and intravenous route (IVR). Both routes of hTERT-MSC transplantation (IVR and IPR) increased the incorporation of BrdU by pancreatic beta -cells compared to control. MSC induced epidermal growth factor (EGF) expression and inhibited proinflammatory cytokines (IFN-gamma and TNF-alpha). FOXA2 and PDX-1 characteristics for pancreatic progenitor cells were activated via AKT/ PDX-1/ FoxO1 signalling pathway.ConclusionThe infusion of hTERT-MSC after partial pancreatectomy (Px) through the IVR and IPR facilitated the proliferation of autochthonous pancreatic beta -cells and provided evidence for a regenerative influence of MSC on the endocrine pancreas. Moderate benefit of IPR over IVR was observed which could be a new treatment option for preventing diabetes mellitus after pancreas surgery.

Harvard-Zitierstil: Khatri, R., Mazurek, S., Petry, S. and Linn, T. (2020) Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway, Stem Cell Research and Therapy, 11(1), Article 497. https://doi.org/10.1186/s13287-020-02007-9

APA-Zitierstil: Khatri, R., Mazurek, S., Petry, S., & Linn, T. (2020). Mesenchymal stem cells promote pancreatic β-cell regeneration through downregulation of FoxO1 pathway. Stem Cell Research and Therapy. 11(1), Article 497. https://doi.org/10.1186/s13287-020-02007-9