2024 Volume No 48 – pages 66-92
Title: Peripheral blood cells enriched by adhesion to CYR61 are heterogenous myeloid modulators of tissue regeneration with early endothelial progenitor characteristics |
Authors: M Herrmann, J Schneidereit, S Wiesner, M Kuric, M Rudert, M Lüdemann, M Srivastava, N Schütze, R Ebert, D Docheva, F Jakob |
Address: IZKF Group Tissue Regeneration in Musculoskeletal Diseases, University Hospital Wuerzburg, 97070 Wuerzburg, Germany; Department of Musculoskeletal Tissue Regeneration, Bernhard-Heine-Center for Locomotion Research & Orthopaedic Hospital Koenig-Ludwig-Haus, University of Wuerzburg, 97074 Wuerzburg, Germany |
E-mail: marietta.herrmann at uni-wuerzburg.de |
Abstract: Introduction: Circulating precursor cell populations of various lineages have been identified with putative functions in tissue regeneration, which may have potential for cell based individual regenerative strategies. We previously demonstrated the enrichment of an angiogenic precursor cell population from peripheral blood mononuclear cells by CYR61, a protein of the CCN family. In vivo, CYR61 mediates the binding of leukocytes and particular monocyte populations at sites of vascular inflammation. Methods: We present an in vitro enrichment system mimicking (patho) physiology and at the same time representing an effective tool for enrichment of the CYR61-binding blood cells and analyzed this cell population in depth. Results: In comparison to fibronectin coating, which is commonly used for selection of endothelial progenitor cells (EPC), CYR61-based enrichment resulted in 8-fold higher cell yields. The CYR61-enriched cell population harbors features of both, early EPC and the monocyte macrophage lineage and therefore represents myeloid angiogenic cells (MAC). This is supported by RNAseq of CYR61-enriched cells and flow cytometry analysis of CD11b expression and acLDL uptake. Functional assays showed that CYR61-enriched MAC have the ability to develop a multinucleated osteoclast-like phenotype as well as to support and participate in angiogenic networks in Matrigel assays. Interestingly, co-cultured CYR61-enriched MAC and their supernatants inhibit mineralization of mesenchymal stromal cells (MSC) during in vitro osteogenic differentiation. Further, osteopontin is highly abundant in our CYR61-enriched MAC as confirmed on mRNA and protein level. Conclusion: The CYR61-enriched MAC, as an autologous source, may represent both a mirror of certain individual regeneration capacities and an important tool to modulate tissue regeneration. |
Keywords: Myeloid angiogenic cells, endothelial progenitor cells, cell therapy, regeneration. |
Publication date: 24th September 2024 |
Copyright policy: © 2024 The Author(s). Published by Forum Multimedia Publishing, LLC. This article is distributed in accordance with Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/). |
Article download: Pages 66-92 (PDF file) |
