Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion
Many experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%–7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to in...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2018-01-01
|
Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2018/9283432 |
id |
doaj-85098531356841c096a614e417243f2e |
---|---|
record_format |
Article |
spelling |
doaj-85098531356841c096a614e417243f2e2020-11-24T23:15:33ZengHindawi LimitedStem Cells International1687-966X1687-96782018-01-01201810.1155/2018/92834329283432Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term ExpansionShuhua Gao0Cheng Xiang1Kairong Qin2Changkai Sun3Department of Electrical and Computer Engineering, National University of Singapore, SingaporeDepartment of Electrical and Computer Engineering, National University of Singapore, SingaporeSchool of Optoelectronic Engineering and Instrumentation Science, Dalian University of Technology, Dalian, ChinaResearch Center for the Control Engineering of Translational Precision Medicine, Dalian University of Technology, Dalian, ChinaMany experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%–7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to investigate the hypoxic effects on MSC expansion quantitatively through mathematical modeling to elucidate the corresponding biological mechanism. A two-compartment model based on ordinary differential equations (ODEs), which incorporate cellular division and senescence via state transition, was developed to describe the MSC expansion process. Parameters of this model were fitted to experimental data and used to interpret the different proliferative capacities of MSCs under hypoxia and normoxia along with model sensitivity analysis. The proposed model was tested on data from two separate experimental studies, and it could reproduce the observed growth characteristics in both conditions. Overall, this compartmental model with a logistic state transition rate was sufficient to explain the experimental findings and highlighted the promotive role of hypoxia in MSC proliferation. This in silico study suggests that hypoxia can enhance MSC long-term expansion mainly by delaying replicative senescence, which is indicated by the slowdown of the state transition rate in our model. Therefore, this explanatory model may provide theoretical proof for the experimentally observed MSC growth superiority under hypoxia and has the potential to further optimize MSC culture protocols for regenerative medicine applications.http://dx.doi.org/10.1155/2018/9283432 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuhua Gao Cheng Xiang Kairong Qin Changkai Sun |
spellingShingle |
Shuhua Gao Cheng Xiang Kairong Qin Changkai Sun Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion Stem Cells International |
author_facet |
Shuhua Gao Cheng Xiang Kairong Qin Changkai Sun |
author_sort |
Shuhua Gao |
title |
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion |
title_short |
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion |
title_full |
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion |
title_fullStr |
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion |
title_full_unstemmed |
Mathematical Modeling Reveals the Role of Hypoxia in the Promotion of Human Mesenchymal Stem Cell Long-Term Expansion |
title_sort |
mathematical modeling reveals the role of hypoxia in the promotion of human mesenchymal stem cell long-term expansion |
publisher |
Hindawi Limited |
series |
Stem Cells International |
issn |
1687-966X 1687-9678 |
publishDate |
2018-01-01 |
description |
Many experimental studies have found that human mesenchymal stem cells (MSCs) in long-term culture exhibited enhanced cell proliferation and prolonged lifespan under hypoxia (around 1%–7% oxygen) against the normoxic condition (about 21% oxygen). Inspired by the experimental findings, we aimed to investigate the hypoxic effects on MSC expansion quantitatively through mathematical modeling to elucidate the corresponding biological mechanism. A two-compartment model based on ordinary differential equations (ODEs), which incorporate cellular division and senescence via state transition, was developed to describe the MSC expansion process. Parameters of this model were fitted to experimental data and used to interpret the different proliferative capacities of MSCs under hypoxia and normoxia along with model sensitivity analysis. The proposed model was tested on data from two separate experimental studies, and it could reproduce the observed growth characteristics in both conditions. Overall, this compartmental model with a logistic state transition rate was sufficient to explain the experimental findings and highlighted the promotive role of hypoxia in MSC proliferation. This in silico study suggests that hypoxia can enhance MSC long-term expansion mainly by delaying replicative senescence, which is indicated by the slowdown of the state transition rate in our model. Therefore, this explanatory model may provide theoretical proof for the experimentally observed MSC growth superiority under hypoxia and has the potential to further optimize MSC culture protocols for regenerative medicine applications. |
url |
http://dx.doi.org/10.1155/2018/9283432 |
work_keys_str_mv |
AT shuhuagao mathematicalmodelingrevealstheroleofhypoxiainthepromotionofhumanmesenchymalstemcelllongtermexpansion AT chengxiang mathematicalmodelingrevealstheroleofhypoxiainthepromotionofhumanmesenchymalstemcelllongtermexpansion AT kairongqin mathematicalmodelingrevealstheroleofhypoxiainthepromotionofhumanmesenchymalstemcelllongtermexpansion AT changkaisun mathematicalmodelingrevealstheroleofhypoxiainthepromotionofhumanmesenchymalstemcelllongtermexpansion |
_version_ |
1725590555963949056 |