| Title |
Hypoxic preconditioning potentiates the trophic effects of mesenchymal stem cells on co-cultured human primary hepatocytes
|
|---|---|
| Published in |
Stem Cell Research & Therapy, December 2015
|
| DOI | 10.1186/s13287-015-0218-7 |
| Pubmed ID | |
| Authors |
Harry H. Qin, Céline Filippi, Song Sun, Sharon Lehec, Anil Dhawan, Robin D. Hughes |
| Abstract |
Mesenchymal stem/stromal cells (MSCs) improve the metabolic function of co-cultured hepatocytes. The present study aimed to further enhance the trophic effects of co-culture with hepatocytes using hypoxic preconditioning (HPc) of the MSCs and also to investigate the underlying molecular mechanisms involved. Human adipose tissue-derived MSCs were subjected to hypoxia (2 % O2; HPc) or normoxia (20 % O2) for 24 h and then co-cultured with isolated human hepatocytes. Assays of metabolic function and apoptosis were performed to investigate the hepatotrophic and anti-apoptotic effects of co-culture. Indirect co-cultures and co-culture with MSC-conditioned medium investigated the role of paracrine factors in the hepatotrophic effects of co-culture. Reactive oxygen species (ROS) activity was antagonised with N-acetylcysteine to investigate whether HPc potentiated the effects of MSCs by intracellular ROS-dependent mechanisms. Tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, and extracellular collagen production was determined and CASP9 and BAX/BCL-2 signalling pathways analysed to investigate the role of soluble factors, extracellular matrix deposition, and apoptosis-associated gene signalling in the effects of co-culture. HPc potentiated the hepatotrophic and anti-apoptotic effects of co-culture by ROS-dependent mechanisms. There was increased MSC TGF-β1 production, and enhanced MSC deposition of extracellular collagen, with reduced synthesis of TNF-α, as well as a downregulation of the expression of pro-apoptotic CASP9, BAX, BID and BLK genes and upregulated expression of anti-apoptotic BCL-2 in hepatocytes. HPc potentiated the trophic and anti-apoptotic effects of MSCs on hepatocytes via mechanisms including intracellular ROS, autocrine TGF-β, extracellular collagen and caspase and BAX/BCL-2 signalling pathways. |
X Demographics
The data shown below were collected from the profiles of 8 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 38% |
| Russia | 1 | 13% |
| Unknown | 4 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 75% |
| Practitioners (doctors, other healthcare professionals) | 2 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 57 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Unknown | 56 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 32% |
| Researcher | 7 | 12% |
| Student > Master | 6 | 11% |
| Other | 5 | 9% |
| Student > Bachelor | 4 | 7% |
| Other | 10 | 18% |
| Unknown | 7 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 12 | 21% |
| Medicine and Dentistry | 10 | 18% |
| Biochemistry, Genetics and Molecular Biology | 10 | 18% |
| Immunology and Microbiology | 4 | 7% |
| Veterinary Science and Veterinary Medicine | 3 | 5% |
| Other | 7 | 12% |
| Unknown | 11 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 25 July 2016.
All research outputs
#6,214,806
of 22,834,308 outputs
Outputs from Stem Cell Research & Therapy
#600
of 2,420 outputs
Outputs of similar age
#97,274
of 387,568 outputs
Outputs of similar age from Stem Cell Research & Therapy
#25
of 57 outputs
Altmetric has tracked 22,834,308 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 2,420 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 387,568 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% of its contemporaries.
We're also able to compare this research output to 57 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.