Stem Cell Research & Therapy (Jan 2022)

Prednisolone and mesenchymal stem cell preloading protect liver cell migration and mitigate extracellular matrix modification in transplanted decellularized rat liver

  • Atefeh Yaghoubi,
  • Negar Azarpira,
  • Saied Karbalay-Doust,
  • Sajad Daneshi,
  • Zahra Vojdani,
  • Tahereh Talaei-Khozani

DOI
https://doi.org/10.1186/s13287-022-02711-8
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 18

Abstract

Read online

Abstract Introduction Regenerative medicine provides promising approaches for treating chronic liver diseases. Previous studies indicate that decellularized liver architecture is damaged by invading non-hepatic inflammatory cells. This study aimed to use anti-inflammatory and regenerative potency of bone marrow-derived mesenchymal stem cells (BM-MSC) and prednisolone for reducing fibrosis and balancing inflammatory cell migration into the decellularized liver scaffold. Material and method The liver was decellularized by perfusing Sodium Lauryl Ether Sulfate (SLES), and nuclei depletion and extracellular matrix (ECM) retention were confirmed by DNA quantification, histochemical, and immunohistochemical assessments. Scaffolds were loaded with BM-MSCs, prednisolone, or a combination of both, implanted at the anatomical place in the rat partial hepatectomized and followed up for 2 and 4 weeks. Results Labeled-MSCs were traced in the transplanted scaffolds; however, they did not migrate into the intact liver. Immunohistochemistry showed that the hepatoblasts, cholangiocytes, stellate, and oval cells invaded into all the scaffolds. Bile ducts were more abundant in the border of the scaffolds and intact liver. Stereological assessments showed a significant reduction in the number of lymphocytes and neutrophils in prednisolone-loaded scaffolds. The regeneration process and angiogenesis were significantly higher in the group treated with cell/prednisolone-loaded bioscaffolds. Collagen fibers were significantly reduced in the scaffolds pre-treated with cell/prednisolone, prednisolone, or BM-MSCs, compared to the control group. Conclusion Loading prednisolone into the scaffolds can be a worthy approach to restrict inflammation after transplantation. Although pre-loading of the scaffolds with a combination of cells/prednisolone could not alleviate inflammation, it played an important role in regeneration and angiogenesis.

Keywords