AccScience Publishing / JCTR / Volume 8 / Issue 1 / DOI: 10.18053/jctres.08.202201.005
REVIEW ARTICLE

Hypoxia-preconditioning of human adipose-derived stem cells enhances cellular proliferation and angiogenesis: A systematic review

John P. Garcia1 Francisco R. Avila1 Ricardo A. Torres1 Karla C. Maita1 Abdullah S. Eldaly1 Brian D. Rinker1 Abba C. Zubair2 Antonio J. Forte1* Rachel Sarabia-Estrada3
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1 Division of Plastic Surgery, Mayo Clinic, Jacksonville, Florida
2 Transfusion Medicines and Stem Cell Therapy, Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA
3 Departments of Neurosurgery; Neuroscience; and, Cancer Biology, Mayo Clinic, Jacksonville, Florida
Submitted: 6 November 2021 | Revised: 7 January 2022 | Accepted: 8 January 2022 | Published: 25 January 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: Human adipose-derived stem cells (hADSCs) have gained attention lately because of their ease of harvesting and ability to be substantially multiplied in laboratory cultures. Stem cells are usually cultured under atmospheric conditions; however, preconditioning stem cells under hypoxic conditions seems beneficial.

Aim: This systematic review aims to investigate the effect of hypoxia preconditioning and its impact on the proliferation and angiogenic capacity of the hADSCs.

Methods: We performed a systematic review by searching PubMed, Scopus, Embase, and Google Scholar databases from all years through March 22, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medical Subject Headings terms “adiposederived stem cell,” “Hypoxia,” “cell proliferation,” and “angiogenesis” guided our search. Only articles written in English using experimental models comparing a preconditioned group against a control group of hADSCs with data on proliferation and angiogenic capacity were included.

Results: Our search yielded a total of 321 articles. 11 articles met our inclusion criteria and were ultimately included in this review. Two studies induced hypoxia using hypoxia-inducible factor-1 alpha stabilizing agents, while nine reached hypoxia by changing oxygen tension conditions around the cells. Four articles conducted in-vivo studies to correlate their in-vitro findings, which proved to be consistent. Although 1 article indicated cell proliferation inhibition with hypoxia preconditioning, the remaining 10 found enhanced proliferation in preconditioned groups compared to controls. All articles showed an enhanced angiogenic capacity of hADSCs after hypoxia preconditioning.

Conclusion: In this review, we found evidence to support hypoxia preconditioning of hADSCs before implantation. Benefits include enhanced cell proliferation with a faster population doubling rate and increased secretion of multiple angiogenic growth factors, enhancing angiogenesis capacity.

Relevance for Patients: Although regenerative therapy is a promising field of study and treatment in medicine, much is still unknown. The potential for angiogenic therapeutics with stem cells is high, but more so, if we discover ways to enhance their natural angiogenic properties. Procedures and pathologies alike require the assistance of angiogenic treatments to improve outcome, such is the case with skin grafts, muscle flaps, skin flaps, or myocardial infarction to mention a few. Enhanced angiogenic properties of stem cells may pave the way for better outcomes and results for patients.

Keywords
adipose-derived stem cells
angiogenesis
cell hypoxia
cell proliferation
growth factors
human stem cells
regenerative medicine
Conflict of interest
The authors declare no conflict of interest
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing