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Hypoxia-Driven Metabolic and Apoptotic Reprogramming Amplifies Immunomodulation in Wharton’s Jelly-Derived Mesenchymal Stem Cells Beyond Bone Marrow Counterparts

ABSTRACT: Mesenchymal stem cells (MSCs) possess immunomodulatory properties that can be harnessed for treating acute graft-versus-host disease (aGVHD). In this study, we compared bone marrow- (BM) and Wharton’s Jelly-derived (WJ) MSCs and investigated how hypoxia preconditioning (1% O₂, 24 h) influences their immunoregulatory function. Using direct co-cultures with activated peripheral blood mononuclear cells from aGVHD patients, we evaluated T-cell proliferation, Treg induction, macrophage polarization, mitochondrial transfer, and MSC apoptosis. Hypoxia-preconditioned WJ-MSCs (WJ-MSCsHYP) more effectively suppressed T-cell proliferation, enhanced Treg differentiation, promoted M2 macrophage polarization, and improved T-cell metabolic balance via mitochondrial transfer. These effects were primarily driven by apoptosis and occurred independently of efferocytosis. Our findings highlight tissue-specific mechanisms underlying MSCs' immunoregulation and reveal that hypoxia enhances the therapeutic potential of WJ-MSCs. This work provides mechanistic insight into MSCs-based interventions and supports WJ-MSCsHYP as a promising cell source for immunomodulatory therapy in inflammatory disorders such as aGVHD.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Umbilical Cord, Stem Cell, Bone Marrow

DISEASE(S): Graft-versus-host Disease

SUBMITTER: Ranjit Sahoo

LAB HEAD: Prof. Ranjit Kumar Sahoo

PROVIDER: PXD074405 | Pride | 2026-02-27

REPOSITORIES: Pride

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			Action	DRS
	BM_MSCs_alone.raw	Raw
	Live_WJ_MSCS_CoCulture_SET1.raw	Raw
	Live_WJ_MSCS_CoCulture_SET2.raw	Raw
	Live_WJ_MSCS_CoCulture_SET3.raw	Raw
	Live_WJ_MSCS_alone_SET2.raw	Raw

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