Improvement of hepatocyte engraftment by co-transplantation with pancreatic islets in hepatocyte transplantation.
cell transplantation
coculture techniques
exosome
hepatocyte engraftment
hepatocyte transplantation
insulin
pancreatic islet transplantation
paracrine communication
Journal
Journal of tissue engineering and regenerative medicine
ISSN: 1932-7005
Titre abrégé: J Tissue Eng Regen Med
Pays: England
ID NLM: 101308490
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
05
12
2020
received:
22
03
2020
accepted:
06
01
2021
pubmed:
24
1
2021
medline:
29
1
2022
entrez:
23
1
2021
Statut:
ppublish
Résumé
Because of the fragility of isolated hepatocytes, extremely poor engraftment of transplanted hepatocytes remains a severe issue in hepatocyte transplantation. Therefore, improving hepatocyte engraftment is necessary to establish hepatocyte transplantation as a standard therapy. Since the pancreatic islets are known to have favorable autocrine effects, we hypothesized that the transplanted islets might influence not only the islets but also the nearby hepatocytes, subsequently promoting engraftment. We evaluated the effects of islet co-transplantation using an analbuminemic rat model (in vivo model). Furthermore, we established a mimicking in vitro model to investigate the underlying mechanisms. In an in vivo model, the hepatocyte engraftment was significantly improved only when the islets were co-transplanted to the nearby hepatocytes (p < 0.001). Moreover, the transplanted hepatocytes appeared to penetrate the renal parenchyma together with the co-transplanted islets. In an in vitro model, the viability of cultured hepatocytes was also improved by coculture with pancreatic islets. Of particular interest, the coculture supernatant alone could also exert beneficial effects comparable to islet coculture. Although insulin, VEGF, and GLP-1 were selected as candidate crucial factors using the Bio-Plex system, beneficial effects were partially counteracted by anti-insulin receptor antibodies. In conclusion, this study demonstrated that islet co-transplantation improves hepatocyte engraftment, most likely due to continuously secreted crucial factors, such as insulin, in combination with providing favorable circumstances for hepatocyte engraftment. Further refinements of this approach, especially regarding substitutes for islets, could be a promising strategy for improving the outcomes of hepatocyte transplantation.
Identifiants
pubmed: 33484496
doi: 10.1002/term.3170
pmc: PMC8048420
doi:
Substances chimiques
Serum Albumin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
361-374Subventions
Organisme : Ministry of Education, Culture, Sports, Science and Technology
Informations de copyright
© 2021 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.
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