Mesenchymal Stem Cell-Macrophage Crosstalk Provides Specific Exosomal Cargo to Direct Immune Response Licensing of Macrophages during Inflammatory Responses

Autor(es)

Naaldijk, Yahaira ; Sherman, Lauren S. ; Turrini, Natalia ; Kenfack, Yannick ; Ratajczak, Mariusz Z. ; Souayah, Nizar ; Rameshwar, Pranela ; Ulrich, Henning

• Tipo de documento: Artigo Científico
• Fonte: STEM CELL REVIEWS AND REPORTS; v. 20, n. 1, p. 19-pg., 2023-10-18.

Resumo

Neurodegenerative diseases (NDDs) continue to be a significant healthcare problem. The economic and social implications of NDDs increase with longevity. NDDs are linked to neuroinflammation and activated microglia and astrocytes play a central role. There is a growing interest for stem cell-based therapy to deliver genes, and for tissue regeneration. The promise of mesenchymal stem cells (MSC) is based on their availability as off-the-shelf source, and ease of expanding from discarded tissues. We tested the hypothesis that MSC have a major role of resetting activated microglial cells. We modeled microglial cell lines by using U937 cell-derived M1 and M2 macrophages. We studied macrophage types, alone, or in a non-contact culture with MSCs. MSCs induced significant release of exosomes from both types of macrophages, but significantly more of the M1 type. RNA sequencing showed enhanced gene expression within the exosomes with the major changes linked to the inflammatory response, including cytokines and the purinergic receptors. Computational analyses of the transcripts supported the expected effect of MSCs in suppressing the inflammatory response of M1 macrophages. The inflammatory cargo of M1 macrophage-derived exosomes revealed involvement of cytokines and purinergic receptors. At the same time, the exosomes from MSC-M2 macrophages were able to reset the classical M2 macrophages to more balanced inflammation. Interestingly, we excluded transfer of purinergic receptor transcripts from the co-cultured MSCs by analyzing these cells for the identified purinergic receptors. Since exosomes are intercellular communicators, these findings provide insights into how MSCs may modulate tissue regeneration and neuroinflammation. (AU)

• Processo FAPESP: 17/23604-0 - Análise da interação entre secretoma de células tronco mesenquimais com micróglias em um modelo de esclerose lateral amiotrófica.
• Beneficiário: Yahaira Maria Naaldijk Palma
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 20/10725-6 - Avaliação dos receptores de purinérgicos na comorbidade do transtorno bipolar e da Doença de Alzheimer
• Beneficiário: Natalia Turrini
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 12/50880-4 - Células-tronco: dos papéis de receptores de cininas e purinas às aplicações terapêuticas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/07366-4 - Receptores de purinas e cininas como alvos de estudo e intervenção terapêutica em doenças neurológicas
• Beneficiário: Alexander Henning Ulrich
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/14343-2 - Células tronco mesenquimais derivadas de polpa dentária em combinação com meio condicionado específico: uma nova abordagem terapêutica para a ELA
• Beneficiário: Yahaira Maria Naaldijk Palma
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado