Multi-omics and systems biology platforms for the standardization and risk assessment of stem cell-derived exosomes therapies

Funding period: 2019-2024
Lead: Jessie Lavoie
Total GRDI funding: $1,190,000

Stem cell therapies are emerging as new treatments for patients with diseases that have currently limited therapeutic options. Extracellular vesicles derived from stem cells or exosomes are novel effectors related to the therapeutic effects of stem cells. Thus, extracellular vesicles are now regarded as new promising therapeutic drug delivery systems for a variety of applications including cancer immunotherapy. This project utilizes multiple 'omic' approaches and systems biology to identify indicators of high quality, safe and effective extracellular vesicles derived from stem cells. The latter are crucial for regulation where the knowledge and comprehension of these parameters are limited. The goal is to enhance the Health Canada's ability to evaluate the quality and safety of these innovative biologics and to provide clinically-compatible manufacturing processes, ultimately providing Canadians with access to high quality medicines.

Publications

  • Cummings SE, Delaney SP, St-Denis Bissonnette F, Stalker A, Muradia G, Mehic J, Graber TE, Alain T, Lavoie JR. 2023. SARS-CoV-2 antigen-carrying extracellular vesicles activate T cell responses in a human immunogenicity model. iScience. Dec 12;27(1):108708. https://doi.org/10.1016/j.isci.2023.108708
  • Gobin J, Muradia G, Mehic J, Westwood C, Couvrette L, Stalker A, Bigelow S, Luebbert CC, St-Denis Bissonnette F, Johnston MJW, Sauvé S, Tam RY, Wang L, Rosu-Myles M, Lavoie JR. 2021. Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell. Stem Cell Res. Ther. 12:e127. https://doi.org/10.1186/s13287-021-02190-3
  • Kirkby M, Popatia AM, Lavoie JR, Wang L. 2023. The Potential of Hormonal Therapies for Treatment of Triple-Negative Breast Cancer. Cancers (Basel). Sep 24;15(19):4702. https://doi.org/10.3390/cancers15194702
  • Mediratta K, El-Sahli S, Marotel M, Awan MZ, Kirkby M, Salkini A, Kurdieh R, Abdisalam S, Shrestha A, Di Censo C, Sulaiman A, McGarry S, Lavoie JR, Liu Z, Lee SH, Li X, Sciumè G, D'Costa VM, Ardolino M, Wang L. 2024. Targeting CD73 with flavonoids inhibits cancer stem cells and increases lymphocyte infiltration in a triple-negative breast cancer mouse model. Front Immunol. Mar 27;15:1366197. https://doi.org/10.3389/fimmu.2024.1366197
  • Munshi A, Mehic J, Creskey M, Gobin J, Gao J, Rigg E, Muradia G, Luebbert CC, Westwood C, Stalker A, Allan DS, Johnston MJW, Cyr T, Rosu-Myles M, Lavoie JR. 2019. A comprehensive proteomics profiling identifies NRP1 as a novel identity marker of human bone marrow mesenchymal stromal cell-derived small extracellular vesicles. Stem Cell Res. Ther. 10(1):e401. https://doi.org/10.1186/s13287-019-1516-2
  • Russell MS, Creskey M, Muralidharan A, Li C, Gao J, Chen W, Larocque L, Lavoie JR, Farnsworth A, Rosu-Myles M, Hashem AM, Yauk CL, Cao J, VanDomselaar G, Cyr T, Li X. 2019. Unveiling integrated functional pathways leading to enhanced respiratory disease associated with inactivated respiratory syncytial viral vaccine. Front Immunol. 10:e597. https://doi.org/10.3389/fimmu.2019.00597
  • St-Denis-Bissonnette F, Cummings SE, Qiu S, Stalker A, Muradia G, Mehic J, Mediratta K, Kaczmarek S, Burger D, Lee SH, Wang L, Lavoie JR. 2023. A clinically relevant large-scale biomanufacturing workflow to produce natural killer cells and natural killer cell-derived extracellular vesicles for cancer immunotherapy. J Extracell Vesicles. Dec;12(12):e12387. https://doi.org/10.1002/jev2.12387
  • St-Denis-Bissonnette F, Khoury R, Mediratta K, El-Sahli S, WangL, Lavoie JR. 2022. Applications of Extracellular Vesicles in Triple-Negative Breast Cancer. Cancers (Basel). 14(2):451. https://doi.org/10.3390/cancers14020451
  • Thulasi Raman SN, Latreille E, Gao J, Zhang W, Wu J, Russell MS, Walrond L, Cyr T, Lavoie JR, Safronetz D, Cao J, Sauvé S, Farnsworth A, Chen W, Shi P-Y, Wang Y, Wang L, Rosu-Myles M, Li X. 2020. Dysregulation of ephrin receptor and PPAR signaling pathways in neural progenitor cells infected by Zika virus. Emerg. Microbes. Infect. 9(1):2046-2060. https://doi.org/10.1080/22221751.2020.1818631

Contact us

For additional information, please contact:
Genomics R&D Initiative
Email: info@grdi-irdg.collaboration.gc.ca