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Cited by 87Mesenchymal stem cell researchExtracellular vesicles in diseasePeriodontal Regeneration and Treatments

Do hypoxia/normoxia culturing conditions change the neuroregulatory profile of Wharton Jelly mesenchymal stem cell secretome?

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Teixeira, Fábio G., Panchalingam, Krishna M., Anjo, Sandra Isabel, Manadas, Bruno, Pereira, Ricardo, Sousa, Nuno, Salgado, António J., Behie, Leo A.·2015·Stem Cell Research & Therapy
DOI 10.1186/s13287-015-0124-zPMC PMC4533943
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Abstract

Introduction: The use of human umbilical cord Wharton Jelly-derived mesenchymal stem cells (hWJ-MSCs) has been considered a new potential source for future safe applications in regenerative medicine. Indeed, the application of hWJ-MSCs into different animal models of disease, including those from the central nervous system, has shown remarkable therapeutic benefits mostly associated with their secretome. Conventionally, hWJ-MSCs are cultured and characterized under normoxic conditions (21 % oxygen tension), although the oxygen levels within tissues are typically much lower (hypoxic) than these standard culture conditions. Therefore, oxygen tension represents an important environmental factor that may affect the performance of mesenchymal stem cells in vivo . However, the impact of hypoxic conditions on distinct mesenchymal stem cell characteristics, such as the secretome, still remains unclear. Methods: In the present study, we have examined the effects of normoxic (21 % O 2 ) and hypoxic (5 % O 2 ) conditions on the hWJ-MSC secretome. Subsequently, we address the impact of the distinct secretome in the neuronal cell survival and differentiation of human neural progenitor cells. Results: The present data indicate that the hWJ-MSC secretome collected from normoxic and hypoxic conditions displayed similar effects in supporting neuronal differentiation of human neural progenitor cells in vitro. However, proteomic analysis revealed that the use of hypoxic preconditioning led to the upregulation of several proteins within the hWJ-MSC secretome. Conclusions: Our results suggest that the optimization of parameters such as hypoxia may lead to the development of strategies that enhance the therapeutic effects of the secretome for future regenerative medicine studies and applications.

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  • These hypoxia-enhanced proteins include thymosin-β, EF-2, UCHL1, clusterin, Prx1 and 14-3-3.

    “These proteins include thymosin-β, EF-2, UCHL1, clusterin, Prx1 and 14-3-3 (Fig. 2) [128].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [128]

  • In neurological diseases, proteomic analysis revealed that hypoxia enhances the expression of proteins associated with neuroprotection, neural survival, differentiation, and axonal and neurite growth compared to the secretome obtained from normoxia-cultured MSCs.

    “proteomic analysis revealed that hypoxia enhances the expression of proteins [128], [129], [130] associated to neuroprotection, neural survival, differentiation, and axonal and neurite growth, when compared to the secretome obtained from normoxia-cultured MSCs [128].”

    From Mesenchymal stem cell secretome for regenerative medicine: Where do we stand? (2025) · cites this paper as [128]

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Authors
Teixeira, F. G., Panchalingam, K. M., Anjo, S. I., Manadas, B., Pereira, R., Sousa, N., Salgado, A. J., & Behie, L. A.
Affiliations
  • University of Minho (PT)
  • University of Calgary (CA)
  • Centro de Neurociências e Biologia Celular (PT)
  • Biocant – Associação de Transferência de Tecnologia (PT)
Corresponding author
Salgado, António J.
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2015-07-24
Volume
6
Issue
1
Pages
133-133
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-015-0124-z
PMC
PMC4533943
OpenAlex
W1596826280
Cited by
87
References
4
Citations by year
2026: 3 · 2025: 6 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 10
FWCI
4.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by)
  • Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
Funders
  • Canada Research Chairs
  • Fundação para a Ciência e a Tecnologia (Ciência 2007, REDE/1506/REM/2005, SFRH/BD/81495/2011)
  • European Regional Development Fund (REDE/1506/REM/2005)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
hypoxia, oxygen partial pressure, secretome, neural progenitor cells, neuronal differentiation, neuronal survival, secretome proteomics, umbilical cord-derived stem cells, neural regulation, regenerative medicine
MeSH terms
Cell Differentiation, Cells, Cultured, Humans, Oxygen, Mass Spectrometry, Cell Hypoxia, Proteomics, Mesenchymal Stem Cell Transplantation, Cell Proliferation, Mesenchymal Stem Cells, Wharton Jelly

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