Differential effects of young and old hematopoietic stem cell niches on bone marrow-derived dendritic cells

Milić, Patrik (author), Justin, Mojca (author), Jazbec Gradišar, Katerina (author), Švajger, Urban (author), Rožman, Primož (author)

Background: Aging is linked to various dysfunctions of the immune system, including the decline of its primary developmental source: the hematopoietic stem cell (HSC) niche. This decline leads to chronic inflammation, increased vulnerability to infections, cancer, autoimmune diseases, and reduced vaccine efficacy. As individuals age, the HSC niche undergoes significant changes, including greater adipocyte accumulation and alterations in the molecular microenvironment, which may influence the development and function of immune cells. Among these cells, the impact of the aging HSC niche on dendritic cell (DC) function is less understood. Heterochronic autologous HSC transplantation is a promising intervention to prevent age-related disorders, contributing to the extension of healthspan and longevity, however, several murine experiments failed to produce the expected results, which led us to presume that the problem lies within the old HSC niche. Therefore, we created in vitro models of young and old HSC niches and examined how these microenvironments affect the differentiation and maturation and functionality of BM-derived DCs (BMDCs). Results: An analysis of the conditioned media from young and aged HSC niches revealed that the environment of aged niches exhibited an increased presence of adiponectin. This media was subsequently utilized in BMDC differentiation and maturation protocols, with their effects closely monitored. Our results indicate that the old HSC niche microenvironment promotes premature BMDC activation, characterized by elevated MHC class II expression and enhanced allostimulatory capacity of BMDCs at their immature stage. Additionally, LPS stimulation of BMDCs, used to induce DC maturation, significantly increased CD86 expression on BMDCs from the aged niche. However, these cells did not show superior allostimulatory capacity compared to their counterparts from the young niche environment. By analyzing the BMDC cytokine profile, we observed that when cultured in aged niche-conditioned media, the BMDCs secreted significantly higher levels of IL-6, indicating a heightened proinflammatory activation state. Conclusions: Collectively, our findings suggest that aging-related changes within the HSC niche can considerably alter DC functionality by disrupting their normal development from BM precursors. These results emphasize the significance of this phenomenon and its implications for immunosenescence.

• Language: English
• Keywords: hematopoietic stem cells, HSC niche, inflammation, aging, dendritic cells, bone marrow-derived dendritic cells, BM adipocytes
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 12 str.
• Numbering: [article. no.] 26, Vol. 22
• PID: 20.500.12556/RUL-171399
• UDC: 602.9
• ISSN on article: 1742-4933
• DOI: 10.1186/s12979-025-00517-9
• COBISS.SI-ID: 241473283
• Publication date in RUL: 25.08.2025

Record is a part of a journal

• Title: Immunity and ageing
• Publisher: BioMed Central
• ISSN: 1742-4933
• COBISS.SI-ID: 3051796

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: hematopoetske matične celice, niša HSC, vnetje, staranje, dendritične celice, dendritične celice kostnega mozga, adipociti kostnega mozga, matične celice

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0371
• Name: Človeške matične celice-napredno zdravljenje s celicami III

• Funder: Young Research Grant