Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice.
Animals
Cell Proliferation
Disease Models, Animal
Hepatectomy
/ adverse effects
Hepatocytes
Humans
Liver
/ cytology
Liver Failure
/ etiology
Liver Regeneration
Male
Mesenchymal Stem Cell Transplantation
Mice
Mice, Inbred BALB C
Mice, Nude
Postoperative Complications
/ etiology
Transplantation, Heterologous
Hepatocyte proliferation
Liver regeneration
Mesenchymal stem cells
Partial hepatectomy
Stem cells
Journal
The Journal of surgical research
ISSN: 1095-8673
Titre abrégé: J Surg Res
Pays: United States
ID NLM: 0376340
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
25
09
2018
revised:
16
01
2019
accepted:
05
02
2019
pubmed:
8
3
2019
medline:
25
1
2020
entrez:
8
3
2019
Statut:
ppublish
Résumé
Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice. Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process. Transgenic GFP-MSCs were administered i.p. 24 h after 70% hepatectomy in BALB/c nude mice, whereas control mice received phosphate-buffered saline. Mice were sacrificed 2, 3, and 5 d after partial hepatectomy. Blood and organs were harvested and metabolic alterations as well as liver regeneration subsequently assessed by liver function tests, multianalyte profiling immunoassays, histology, and immunostaining. Hepatocyte and sinusoidal endothelial cell proliferation were significantly increased after partial hepatectomy in mice receiving MSC compared to control mice (Hepatocyte postoperative day 3, P < 0.01; endothelial cell postoperative day 5, P < 0.05). Hepatocyte fat accumulation correlated inversely with hepatocyte proliferation (r Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.
Sections du résumé
BACKGROUND
Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice.
METHODS
Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process. Transgenic GFP-MSCs were administered i.p. 24 h after 70% hepatectomy in BALB/c nude mice, whereas control mice received phosphate-buffered saline. Mice were sacrificed 2, 3, and 5 d after partial hepatectomy. Blood and organs were harvested and metabolic alterations as well as liver regeneration subsequently assessed by liver function tests, multianalyte profiling immunoassays, histology, and immunostaining.
RESULTS
Hepatocyte and sinusoidal endothelial cell proliferation were significantly increased after partial hepatectomy in mice receiving MSC compared to control mice (Hepatocyte postoperative day 3, P < 0.01; endothelial cell postoperative day 5, P < 0.05). Hepatocyte fat accumulation correlated inversely with hepatocyte proliferation (r
CONCLUSIONS
Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.
Identifiants
pubmed: 30844633
pii: S0022-4804(19)30086-1
doi: 10.1016/j.jss.2019.02.010
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
191-200Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.