Therapeutic effects of adipose-derived mesenchymal stem cells against brain death-induced remote organ damage and post-heart transplant acute rejection

Hon Kan Yip, Mel S. Lee, Cheuk Kwan Sun, Kuan Hung Chen, Han Tan Chai, Pei Hsun Sung, Kun Chen Lin, Sheung Fat Ko, Chun Man Yuen, Chu Feng Liu, Pei Lin Shao, Fan Yen Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

20 Scopus citations

Abstract

We tested the hypothesis that allogenic adipose-derived mesenchymal stem cells (ADMSCs) alleviated brain death (BD)-induced remote organ damage and events of post heart-transplant acute rejection. To determine the impact of BD on remote organ damage, adult-male F344 rats (n=24) were categorized sham-control (SC), BD and BDMSC (allogenic ADMSC/1.2 × 106 cells/derived from F344 by intravenous transfusion 3 h after BD procedure). To determine the protective effect of allogenic ADMSCs, animals (n=8/each group in F344/Lewis) were categorized into groups BD-T(F344 heart transplanted into Lewis by 6h after BD), BD-TMSC(D1/3) (BD induction for 6h then heart transplantation, and allogenic ADMSCs transfusion at days 1 and 5 after heart transplantation), BD-TMSC(3h) (BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD) and BD-TMSC(3h, D1/3) [BD + ADMSC/1.2 × 106 cells at 3h and heart transplantation at 6h after BD, then ADMSC therapy by days 1/3]. At day 5 post procedure, liver, kidney and heart specimens showed higher molecular-cellular levels of inflammation, immune reaction, apoptosis and fibrosis in BD than in SC that were reversed in BDMSC (all P < 0.0001). These molecular-cellular expressions and circulating/splenic levels of innate/adoptive immune cells were higher in BD-T, lowest in BD-TMSC(3h, D1/3) and higher BD-TMSC(3h) in than BD-TMSC(D1/3), whereas heart function showed an opposite pattern among the four groups (all P < 0.001). In conclusion, ADMSCs suppressed BD-caused remote organ damage and heart-transplant rejection.

Original languageEnglish
Pages (from-to)108692-108711
Number of pages20
JournalOncotarget
Volume8
Issue number65
DOIs
StatePublished - 2017

Bibliographical note

Publisher Copyright:
© Yip et al.

Keywords

  • Brain death
  • Heart transplantation
  • Immunogenicity
  • Inflammation
  • Remote organ damage

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