June 2025 - Christian Behm

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Priv.-Doz. Christian Behm, PhD

MedUni Wien RESEARCHER OF THE MONTH June 2025

Mesenchymal stromal cells (MSCs) are multipotent progenitor cells found in various human tissues, including bone marrow, umbilical cord, adipose tissue, periodontal ligament (PDL), and gingiva. Due to their regenerative and immunomodulatory potential, MSCs are being explored in numerous in vivo studies to treat diseases like type 1 diabetes, stroke, Crohn's disease, periodontitis, and cancer. However, their therapeutic effectiveness is limited by their heterogeneity, which arises from tissue source, donor variation, and even differences between individual cells.

Single-cell transcriptomics has been applied to better understand this heterogeneity. Previous studies compared MSCs from different tissues and donors, making it difficult to distinguish tissue-specific from donor-specific variation. In our study, we isolated and cultured MSCs from both PDL and gingiva of the same healthy individuals. This allowed us to separate tissue-associated from donor-associated heterogeneity.

Our analysis revealed tissue-specific subpopulations with distinct gene expression patterns, as well as shared cell populations across both tissues. Pathway and protein interaction analyses showed that differences were limited to a few cellular processes.

In summary, our findings demonstrate both tissue- and donor-dependent transcriptomic differences in dental MSCs, which are confined to specific cellular pathways. Identifying shared and tissue-specific subpopulations highlights the complexity within dental MSC populations and supports the value of single-cell analysis to ensure consistent cell characteristics before clinical application.

Selected Literature

1. Behm C, Miłek O, Schwarz K, et al (2024) Heterogeneity in Dental Tissue–Derived MSCs Revealed by Single-Cell RNA-seq. J Dent Res. https://doi.org/10.1177/00220345241271997
2. Viswanathan S, SHI Y, GALIPEAU J, et al (2019) Mesenchymal stem versus stromal cells: International Society for Cellular Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy 21:1019–1024. https://doi.org/10.1016/j.jcyt.2019.08.002
3. Seo B-M, Miura M, Gronthos S, et al (2004) Investigation of multipotent postnatal stem cells from human periodontal ligament. The Lancet 364:149–155. https://doi.org/10.1016/S0140-6736(04)16627-0
4. Mitrano TI, Grob MS, Carrión F, et al (2010) Culture and characterization of mesenchymal stem cells from human gingival tissue. J Periodontol 81:917–925. https://doi.org/10.1902/JOP.2010.090566
5. Levy O, Kuai R, Siren EMJ, et al (2020) Shattering barriers toward clinically meaningful MSC therapies. Sci Adv 6:. https://doi.org/10.1126/SCIADV.ABA6884
6. Costa LA, Eiro N, Fraile M, et al (2021) Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses. Cell Mol Life Sci 78:447–467. https://doi.org/10.1007/S00018-020-03600-0
7. Wang Z, Chai C, Wang R, et al (2021) Single-cell transcriptome atlas of human mesenchymal stem cells exploring cellular heterogeneity. Clin Transl Med 11:. https://doi.org/10.1002/CTM2.650
8. Zhang Q, Xu Y, Xu J (2022) Editorial: Targeting Heterogeneity of Mesenchymal Stem Cells. Front Cell Dev Biol 10:. https://doi.org/10.3389/FCELL.2022.894008
9. Zhang C, Han X, Liu J, et al (2022) Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells. Genomics Proteomics Bioinformatics 20:70–86. https://doi.org/10.1016/J.GPB.2022.01.005
10. Barrett AN, Fong CY, Subramanian A, et al (2019) Human Wharton’s Jelly Mesenchymal Stem Cells Show Unique Gene Expression Compared with Bone Marrow Mesenchymal Stem Cells Using Single-Cell RNA-Sequencing. Stem Cells Dev 28:196–211. https://doi.org/10.1089/SCD.2018.0132
11. Huang Y, Li Q, Zhang K, et al (2019) Single cell transcriptomic analysis of human mesenchymal stem cells reveals limited heterogeneity. Cell Death Dis 10:. https://doi.org/10.1038/S41419-019-1583-4
12. Zhou W, Lin J, Zhao K, et al (2019) Single-Cell Profiles and Clinically Useful Properties of Human Mesenchymal Stem Cells of Adipose and Bone Marrow Origin. Am J Sports Med 47:1722–1733. https://doi.org/10.1177/0363546519848678
13. Medrano-Trochez C, Chatterjee P, Pradhan P, et al (2021) Single-cell RNA-seq of out-of-thaw mesenchymal stromal cells shows tissue-of-origin differences and inter-donor cell-cycle variations. Stem Cell Res Ther 12:. https://doi.org/10.1186/S13287-021-02627-9
14. Lee S, Chen D, Park M, et al (2022) Single-Cell RNA Sequencing Analysis of Human Dental Pulp Stem Cell and Human Periodontal Ligament Stem Cell. J Endod 48:240–248. https://doi.org/10.1016/J.JOEN.2021.11.005
15. Xu H, Dai Q, Wang X, et al (2023) ScRNA-seq links dental fibroblasts heterogeneity with mechanoresponsiveness. J Periodontal Res 58:. https://doi.org/10.1111/JRE.13139
16. Yang Y, Alves T, Miao MZ, et al (2024) Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells. J Dent Res 103:71–80. https://doi.org/10.1177/00220345231205283/ASSET/IMAGES/LARGE/10.1177_00220345231205283-FIG4.JPEG