Identification of ALP+/CD73+ defining markers for enhanced osteogenic potential in human adipose-derived mesenchymal stromal cells by mass cytometry

Autor: Manfred Claassen, Sonja Märsmann, Jan A. Plock, Hans-Christoph Pape, Vinko Tosevski, Johanna Buschmann, Andrè A. Barth, Paolo Cinelli, Daisy D. Canepa, Benjamin Eggerschwiler, Elisa A. Casanova, Sascha Halvachizadeh, Eirini Arvaniti
Přispěvatelé: University of Zurich, Cinelli, Paolo
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Multidimensional analysis
Stromal cell
Stromal vascular fraction
Cell subpopulation
Cell
Medicine (miscellaneous)
Adipose tissue
610 Medicine & health
Biology
1301 Biochemistry
Genetics and Molecular Biology (miscellaneous)
Biochemistry
Genetics and Molecular Biology (miscellaneous)
lcsh:Biochemistry
1307 Cell Biology
Osteogenesis
medicine
Humans
lcsh:QD415-436
Mass cytometry
10266 Clinic for Reconstructive Surgery
Osteogenic potential
Cells
Cultured
lcsh:R5-920
Research
Adipose-derived mesenchymal stromal cells
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
2701 Medicine (miscellaneous)
Cell Biology
Cell biology
10021 Department of Trauma Surgery
medicine.anatomical_structure
Adipose Tissue
1313 Molecular Medicine
Molecular Medicine
CyTOF
Stem cell
lcsh:Medicine (General)
Cytometry
Zdroj: Stem Cell Research & Therapy, 12 (1)
Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-16 (2021)
Stem Cell Research & Therapy
DOI: 10.3929/ethz-b-000460925
Popis: Background The impressive progress in the field of stem cell research in the past decades has provided the ground for the development of cell-based therapy. Mesenchymal stromal cells obtained from adipose tissue (AD-MSCs) represent a viable source for the development of cell-based therapies. However, the heterogeneity and variable differentiation ability of AD-MSCs depend on the cellular composition and represent a strong limitation for their use in therapeutic applications. In order to fully understand the cellular composition of MSC preparations, it would be essential to analyze AD-MSCs at single-cell level. Method Recent advances in single-cell technologies have opened the way for high-dimensional, high-throughput, and high-resolution measurements of biological systems. We made use of the cytometry by time-of-flight (CyTOF) technology to explore the cellular composition of 17 human AD-MSCs, interrogating 31 markers at single-cell level. Subcellular composition of the AD-MSCs was investigated in their naïve state as well as during osteogenic commitment, via unsupervised dimensionality reduction as well as supervised representation learning approaches. Result This study showed a high heterogeneity and variability in the subcellular composition of AD-MSCs upon isolation and prolonged culture. Algorithm-guided identification of emerging subpopulations during osteogenic differentiation of AD-MSCs allowed the identification of an ALP+/CD73+ subpopulation of cells with enhanced osteogenic differentiation potential. We could demonstrate in vitro that the sorted ALP+/CD73+ subpopulation exhibited enhanced osteogenic potential and is moreover fundamental for osteogenic lineage commitment. We finally showed that this subpopulation was present in freshly isolated human adipose-derived stromal vascular fractions (SVFs) and that could ultimately be used for cell therapies. Conclusion The data obtained reveal, at single-cell level, the heterogeneity of AD-MSCs from several donors and highlight how cellular composition impacts the osteogenic differentiation capacity. The marker combination (ALP/CD73) can not only be used to assess the differentiation potential of undifferentiated AD-MSC preparations, but also could be employed to prospectively enrich AD-MSCs from the stromal vascular fraction of human adipose tissue for therapeutic applications.
Stem Cell Research & Therapy, 12 (1)
Databáze: OpenAIRE
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