A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components - PubMed

Affiliations

• PMID: 26663569
• DOI: 10.1111/ajt.13537

Free article

A Distinct Subpopulation of Bone Marrow Mesenchymal Stem Cells, Muse Cells, Directly Commit to the Replacement of Liver Components

H Katagiri et al. Am J Transplant. 2016 Feb.

Free article

Abstract

Genotyping graft livers by short tandem repeats after human living-donor liver transplantation (n = 20) revealed the presence of recipient or chimeric genotype cases in hepatocytes (6 of 17, 35.3%), sinusoidal cells (18 of 18, 100%), cholangiocytes (15 of 17, 88.2%) and cells in the periportal areas (7 of 8, 87.5%), suggesting extrahepatic cell involvement in liver regeneration. Regarding extrahepatic origin, bone marrow mesenchymal stem cells (BM-MSCs) have been suggested to contribute to liver regeneration but compose a heterogeneous population. We focused on a more specific subpopulation (1-2% of BM-MSCs), called multilineage-differentiating stress-enduring (Muse) cells, for their ability to differentiate into liver-lineage cells and repair tissue. We generated a physical partial hepatectomy model in immunodeficient mice and injected green fluorescent protein (GFP)-labeled human BM-MSC Muse cells intravenously (n = 20). Immunohistochemistry, fluorescence in situ hybridization and species-specific polymerase chain reaction revealed that they integrated into regenerating areas and expressed liver progenitor markers during the early phase and then differentiated spontaneously into major liver components, including hepatocytes (≈74.3% of GFP-positive integrated Muse cells), cholangiocytes (≈17.7%), sinusoidal endothelial cells (≈2.0%), and Kupffer cells (≈6.0%). In contrast, the remaining cells in the BM-MSCs were not detected in the liver for up to 4 weeks. These results suggest that Muse cells are the predominant population of BM-MSCs that are capable of replacing major liver components during liver regeneration.

Keywords: basic (laboratory) research; hepatology; liver transplantation; living donor; regenerative medicine; science; stem cells; translational research.

Similar articles

• Muse Cells, Nontumorigenic Pluripotent-Like Stem Cells, Have Liver Regeneration Capacity Through Specific Homing and Cell Replacement in a Mouse Model of Liver Fibrosis.

  Iseki M, Kushida Y, Wakao S, Akimoto T, Mizuma M, Motoi F, Asada R, Shimizu S, Unno M, Chazenbalk G, Dezawa M. Iseki M, et al. Cell Transplant. 2017 May 9;26(5):821-840. doi: 10.3727/096368916X693662. Epub 2016 Nov 2. Cell Transplant. 2017. PMID: 27938474 Free PMC article.

• Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra-small partial liver transplantation model.

  Shono Y, Kushida Y, Wakao S, Kuroda Y, Unno M, Kamei T, Miyagi S, Dezawa M. Shono Y, et al. Am J Transplant. 2021 Jun;21(6):2025-2039. doi: 10.1111/ajt.16461. Epub 2021 Jan 15. Am J Transplant. 2021. PMID: 33350582 Free PMC article.

• Liver Regeneration Supported by Muse Cells.

  Nishizuka SS, Suzuki Y, Katagiri H, Takikawa Y. Nishizuka SS, et al. Adv Exp Med Biol. 2018;1103:219-241. doi: 10.1007/978-4-431-56847-6_12. Adv Exp Med Biol. 2018. PMID: 30484232 Review.

• Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice.

  Fujii H, Hirose T, Oe S, Yasuchika K, Azuma H, Fujikawa T, Nagao M, Yamaoka Y. Fujii H, et al. J Hepatol. 2002 May;36(5):653-9. doi: 10.1016/s0168-8278(02)00043-0. J Hepatol. 2002. PMID: 11983449

• Muse Cells Provide the Pluripotency of Mesenchymal Stem Cells: Direct Contribution of Muse Cells to Tissue Regeneration.

  Dezawa M. Dezawa M. Cell Transplant. 2016;25(5):849-61. doi: 10.3727/096368916X690881. Epub 2016 Feb 15. Cell Transplant. 2016. PMID: 26884346 Review.

Cited by

• Sinusoidal communication in liver fibrosis and regeneration.

  Marrone G, Shah VH, Gracia-Sancho J. Marrone G, et al. J Hepatol. 2016 Sep;65(3):608-17. doi: 10.1016/j.jhep.2016.04.018. Epub 2016 May 2. J Hepatol. 2016. PMID: 27151183 Free PMC article. Review.

• Promising Markers in the Context of Mesenchymal Stem/Stromal Cells Subpopulations with Unique Properties.

  Smolinska A, Bzinkowska A, Rybkowska P, Chodkowska M, Sarnowska A. Smolinska A, et al. Stem Cells Int. 2023 Sep 20;2023:1842958. doi: 10.1155/2023/1842958. eCollection 2023. Stem Cells Int. 2023. PMID: 37771549 Free PMC article. Review.

• Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions.

  Nguyen LT, Tran NT, Than UTT, Nguyen MQ, Tran AM, Do PTX, Chu TT, Nguyen TD, Bui AV, Ngo TA, Hoang VT, Hoang NTM. Nguyen LT, et al. Stem Cell Res Ther. 2022 Jan 10;13(1):15. doi: 10.1186/s13287-021-02694-y. Stem Cell Res Ther. 2022. PMID: 35012671 Free PMC article.

• Human Muse Cells Reconstruct Neuronal Circuitry in Subacute Lacunar Stroke Model.

  Uchida H, Niizuma K, Kushida Y, Wakao S, Tominaga T, Borlongan CV, Dezawa M. Uchida H, et al. Stroke. 2017 Feb;48(2):428-435. doi: 10.1161/STROKEAHA.116.014950. Epub 2016 Dec 20. Stroke. 2017. PMID: 27999136 Free PMC article.

• In vitro Culture of Naïve Human Bone Marrow Mesenchymal Stem Cells: A Stemness Based Approach.

  Pal B, Das B. Pal B, et al. Front Cell Dev Biol. 2017 Aug 23;5:69. doi: 10.3389/fcell.2017.00069. eCollection 2017. Front Cell Dev Biol. 2017. PMID: 28884113 Free PMC article. Review.

Publication types

MeSH terms

LinkOut - more resources

• Full Text Sources

  • Elsevier Science
  • Ovid Technologies, Inc.
  • Wiley

• Medical

  • MedlinePlus Health Information