Transplantation of SDF-1α-loaded liver extracellular matrix repopulated with autologous cells attenuated liver fibrosis in a rat model

Authors

  • Mostafa Najar-Asl Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Anatomical Sciences, School of Medical Sciences, Baqiyatallah University, Tehran, Iran https://orcid.org/0000-0003-1418-9206
  • Hossein Bahadoran Department of Anatomical Sciences, School of Medical Sciences, Baqiyatallah University, Tehran, Iran. Tel: +98 9124276200; E-mail: bahadoran.h@bmsu.ac.ir https://orcid.org/0000-0002-8862-5536
  • Mohammad-Hossein Asadi Department of Anatomical Sciences, School of Medical Sciences, Baqiyatallah University, Tehran, Iran https://orcid.org/0000-0002-3251-1898
  • Mona Saheli Department of Anatomical Sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran https://orcid.org/0000-0001-7517-0117
  • Mohammad-Hassan Asghari Animal Core Facility, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Tehran, Iran https://orcid.org/0000-0003-4331-8505
  • Niloofar Sodeifi Department of Andrology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran https://orcid.org/0000-0001-7843-9679
  • Mohammad Kazemi Ashtiani Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran https://orcid.org/0000-0002-5709-4277
  • Massoud Vosough Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran https://orcid.org/0000-0001-5924-4366
  • Hossein Baharvand Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran, Iran https://orcid.org/0000-0001-6528-3687
  • Abbas Piryaei Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Tel: +98 2123872555; E-mail: piryae@sbmu.ac.ir https://orcid.org/0000-0002-3182-6214

DOI:

https://doi.org/10.17179/excli2022-4761

Keywords:

liver extracellular matrix scaffold, stromal derived factor-1α, granulocyte colony stimulating factor, endogenous progenitor cells mobilization, in vivo tissue engineering, liver fibrosis

Abstract

Cell-based therapy and tissue engineering are promising substitutes for liver transplantation to cure end-stage liver disorders. However, the limited sources for healthy and functional cells and poor engraftment rate are main challenges to the cell-based therapy approach. On the other hand, feasibility of production and size of bioengineered tissues are primary bottlenecks in tissue engineering. Here, we induce regeneration in a rat fibrotic liver model by transplanting a natural bioengineered scaffold with a native microenvironment repopulated with autologous stem/progenitor cells. In the main experimental group, a 1 mm3 stromal derived factor-1α (SDF-1α; S) loaded scaffold from decellularized liver extracellular matrix (LEM) was transplanted (Tx) into a fibrotic liver and the endogenous stem/progenitor cells were mobilized via granulocyte colony stimulating factor (G-CSF; G) therapy. Four weeks after transplantation, changes in liver fibrosis and necrosis, efficacy of cell engraftment and differentiation, vasculogenesis, and liver function recovery were assessed in this (LEM-TxSG) group and compared to the other groups. We found significant reduction in liver fibrosis stage in the LEM-TxSG, LEM-TxS and LEM-TxG groups compared to the control (fibrotic) group. Liver necrosis grade, and alanine transaminase (ALT) and aspartate transaminase (AST) levels dramatically reduced in all experimental groups compared to the control group. However, the number of engrafted cells into the transplanted scaffold and ratio of albumin (Alb) positive cells per total incorporated cells were considerably higher in the LEM-TxSG group compared to the LEM-Tx, LEM-TxS and LEM-TxG groups. Serum Alb levels increased in the LEM-Tx, LEM-TxS, and LEM-TxG groups, and was highest in the LEM-TxSG group, which was significantly more than the fibrotic group. Small vessel formation in the LEM-TxSG group was significantly higher than the LEM-Tx and LEM-TxS groups. Totally, these findings support application of the in vivo tissue engineering approach as a possible novel therapeutic strategy for liver fibrosis.

Author Biography

Mona Saheli, Department of Anatomical Sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Department of Anatomical Sciences, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Published

2022-04-22

How to Cite

Najar-Asl, M., Bahadoran, H., Asadi, M.-H., Saheli, M., Asghari, M.-H., Sodeifi, N., Ashtiani, M. K., Vosough, M., Baharvand, H., & Piryaei, A. (2022). Transplantation of SDF-1α-loaded liver extracellular matrix repopulated with autologous cells attenuated liver fibrosis in a rat model . EXCLI Journal, 21, 704–721. https://doi.org/10.17179/excli2022-4761

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