3DMSCs.com

Research library

A curated, non-exhaustive list of peer-reviewed papers that examine three-dimensional MSC culture, the MSC secretome, or extracellular vesicles harvested from 3D systems. Each entry includes a one-line summary of the central finding and links to PubMed and the publisher of record.

Editorial note. Inclusion does not imply that every claim in a paper has been independently verified. Readers should review primary sources before drawing conclusions. Identifiers should resolve via the linked services; if a link breaks, search the title in PubMed directly.

Reviews and primers

  1. Sart S, Tsai AC, Li Y, Ma T. Three-dimensional aggregates of mesenchymal stem cells: cellular mechanisms, biological properties, and applications. Tissue Engineering Part B: Reviews. 2014;20(5):365–380.
    DOI: 10.1089/ten.teb.2013.0537 · PubMed

    Comprehensive review of mechanisms by which spheroid culture changes MSC phenotype, including hypoxic core formation, cell-cell contact signalling, and ECM remodelling.

  2. Cesarz Z, Tamama K. Spheroid culture of mesenchymal stem cells. Stem Cells International. 2016;2016:9176357.
    DOI: 10.1155/2016/9176357 · PubMed

    Open-access review covering spheroid formation methods and observed shifts in stemness, paracrine factor expression, and survival under transplantation.

  3. Phinney DG, Pittenger MF. Concise Review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35(4):851–858.
    DOI: 10.1002/stem.2575 · PubMed

    Frames MSC-derived EVs as carriers of much of the paracrine activity historically attributed to whole-cell MSC products and surveys characterisation methods.

  4. Théry C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018). Journal of Extracellular Vesicles. 2018;7(1):1535750.
    DOI: 10.1080/20013078.2018.1535750 · PubMed

    Community consensus guidance on terminology, isolation, and reporting standards for EV studies. Recommended baseline reading for anyone interpreting EV literature.

  5. Ferreira JR, Teixeira GQ, Santos SG, Barbosa MA, Almeida-Porada G, Gonçalves RM. Mesenchymal stromal cell secretome: influencing therapeutic potential by cellular pre-conditioning. Frontiers in Immunology. 2018;9:2837.
    DOI: 10.3389/fimmu.2018.02837 · PubMed

    Reviews how culture conditions, including 3D format and hypoxia, modify the MSC secretome and downstream functional readouts.

3D culture biology of MSCs

  1. Bartosh TJ, Ylöstalo JH, Mohammadipoor A, et al. Aggregation of human mesenchymal stromal cells (MSCs) into 3D spheroids enhances their antiinflammatory properties. Proceedings of the National Academy of Sciences. 2010;107(31):13724–13729.
    DOI: 10.1073/pnas.1008117107 · PubMed

    Foundational paper showing that aggregating MSCs into 3D spheroids upregulates anti-inflammatory genes (TSG-6, STC-1) compared with matched 2D monolayer cultures.

  2. Bartosh TJ, Ylöstalo JH, Bazhanov N, Kuhlman J, Prockop DJ. Dynamic compaction of human mesenchymal stem/precursor cells into spheres self-activates caspase-dependent IL1 signaling. Stem Cells. 2013;31(11):2443–2456.
    DOI: 10.1002/stem.1499 · PubMed

    Mechanistic study showing that the act of compacting into a sphere itself triggers signalling cascades that drive enhanced secretion of modulators including PGE2 and TSG-6.

  3. Frith JE, Thomson B, Genever PG. Dynamic three-dimensional culture methods enhance mesenchymal stem cell properties and increase therapeutic potential. Tissue Engineering Part C: Methods. 2010;16(4):735–749.
    DOI: 10.1089/ten.tec.2009.0432 · PubMed

    Compares static and dynamic 3D culture methods and reports better retention of MSC marker expression and differentiation capacity than matched monolayer cultures.

  4. Murphy KC, Hoch AI, Harvestine JN, Zhou D, Leach JK. Mesenchymal stem cell spheroids retain osteogenic phenotype through α2β1 signaling. Stem Cells Translational Medicine. 2016;5(9):1229–1237.
    DOI: 10.5966/sctm.2015-0412 · PubMed

    Identifies α2β1 integrin signalling as one route by which spheroid-cultured MSCs preserve differentiation capacity that is lost during prolonged 2D expansion.

  5. Bhang SH, Cho SW, La WG, et al. Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. Biomaterials. 2011;32(11):2734–2747.
    DOI: 10.1016/j.biomaterials.2010.12.035 · PubMed

    Reports higher pro-angiogenic factor expression and improved in vivo retention from spheroid-form adipose-derived MSCs versus dissociated cells.

  6. Bhang SH, Lee S, Shin JY, Lee TJ, Kim BS. Transplantation of cord blood mesenchymal stem cells as spheroids enhances vascularization. Tissue Engineering Part A. 2012;18(19–20):2138–2147.
    DOI: 10.1089/ten.tea.2011.0640 · PubMed

    Comparative in vivo study showing that cord-blood MSCs delivered as spheroids show better paracrine vascularisation activity than the same cells delivered as dissociated suspensions.

  7. Potapova IA, Gaudette GR, Brink PR, et al. Mesenchymal stem cells support migration, extracellular matrix invasion, proliferation, and survival of endothelial cells in vitro. Stem Cells. 2007;25(7):1761–1768.
    DOI: 10.1634/stemcells.2007-0022 · PubMed

    Early demonstration that MSCs cultured as 3D spheroids secrete a paracrine cocktail that supports endothelial migration and survival in coculture assays.

3D-derived extracellular vesicles

  1. Haraszti RA, Miller R, Stoppato M, et al. Exosomes produced from 3D cultures of MSCs by tangential flow filtration show higher yield and improved activity. Molecular Therapy. 2018;26(12):2838–2847.
    DOI: 10.1016/j.ymthe.2018.09.015 · PubMed

    Reports that 3D-cultured MSCs combined with tangential-flow-filtration recovery yield substantially more vesicles per cell than 2D culture, with measurably higher functional activity per particle in in vitro assays.

  2. Cao J, Wang B, Tang T, et al. Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury. Stem Cell Research & Therapy. 2020;11(1):206.
    DOI: 10.1186/s13287-020-01719-2 · PubMed

    Side-by-side comparison of exosome yield from 2D and 3D systems with downstream functional assays in a kidney-injury preclinical model.

  3. Yan L, Wu X. Exosomes produced from 3D cultures of umbilical cord mesenchymal stem cells in a hollow-fiber bioreactor show improved osteochondral regeneration activity. Cell Biology and Toxicology. 2020;36(2):165–178.
    DOI: 10.1007/s10565-019-09504-5 · PubMed

    Hollow-fiber bioreactor production of UC-MSC EVs is reported to give higher yield and stronger activity in osteochondral assays than matched 2D production.

  4. Kim M, Yun HW, Park DY, Choi BH, Min BH. Three-dimensional spheroid culture increases exosome secretion from mesenchymal stem cells. Tissue Engineering and Regenerative Medicine. 2018;15(4):427–436.
    DOI: 10.1007/s13770-018-0139-5 · PubMed

    Quantifies an increase in exosome release per cell when MSCs are cultured as spheroids compared with matched 2D conditions.

  5. Patel DB, Gray KM, Santharam Y, Lamichhane TN, Stroka KM, Jay SM. Impact of cell culture parameters on production and vascularization bioactivity of mesenchymal stem cell-derived extracellular vesicles. Bioengineering & Translational Medicine. 2017;2(2):170–179.
    DOI: 10.1002/btm2.10065 · PubMed

    Systematic study of how culture parameters — including dimensional format — change EV production rate and vascularisation activity per particle.

Citation list curated 2026. Updated occasionally. If you spot a broken link or a paper that should be added, email the address listed on the about page when published.