Concurrent hypoxia and apoptosis imparts immune programming potential in mesenchymal stem cells: Lesson from acute graft-versus-host-disease model.

Mesenchymal Stem Cells / metabolism Humans Graft vs Host Disease / immunology Apoptosis Cell Hypoxia Coculture Techniques Cell Differentiation T-Lymphocytes, Regulatory / immunology Cell Proliferation Macrophages / immunology Cells, Cultured Male Female Adult

Acute graft-versus-host-disease Apoptosis Bone marrow Hypoxia Immunomodulation Mesenchymal stem cells Wharton’s Jelly

Journal

Stem cell research & therapy

ISSN: 1757-6512

Titre abrégé: Stem Cell Res Ther

Pays: England

ID NLM: 101527581

Informations de publication

Date de publication:
29 Oct 2024

Historique:

received: 29 04 2024

accepted: 18 09 2024

medline: 29 10 2024

pubmed: 29 10 2024

entrez: 29 10 2024

Statut: epublish

Résumé

Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy. Human MSCs were derived from bone marrow (BM) and Wharton's Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined. Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCs Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD.

Sections du résumé

BACKGROUND BACKGROUND

METHODS METHODS

Human MSCs were derived from bone marrow (BM) and Wharton's Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined.

RESULTS RESULTS

Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCs

CONCLUSION CONCLUSIONS

Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD.

Identifiants

DOI: 10.1186/s13287-024-03947-2 PMID: 39468660

pubmed: 39468660

doi: 10.1186/s13287-024-03947-2

pii: 10.1186/s13287-024-03947-2

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

381

Subventions

Organisme : Indian Council of Medical Research

ID : 2021/14763

Informations de copyright

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