Artificial Tertiary Lymphoid Structures: Exploring Mesenchymal Stromal Cells as a Platform for Immune Niche Formation.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization. Single-cell RNA sequencing revealed a distinct subpopulation of MSCs expressing key fibroblastic reticular cell (FRC)-associated markers, including IL-7, PDPN, and IL-15, though lacking follicular dendritic cell (FDC) markers. TNF-α stimulation, but not LTα2β1, further enhanced FRC marker expression (IL-7, PDPN, and ICAM1). Notably, in 3D spheroid co-culture with lymphocytes, MSCs upregulated additional FRC markers, specifically CCL21. Upon implantation into adipose tissue, MSC-lymphocyte organoids maintained structural integrity and showed extensive T-cell infiltration and partial vascularization after 15 days in vivo, although organized B-cell follicles and FDC markers were still lacking. These findings highlight MSCs' intrinsic ability to adopt an FRC-like phenotype that supports T-cell and HEV organization, suggesting that further optimization, including genetic modification, may be needed to achieve an FDC phenoty

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.