Science

Paracrine Therapeutics is dedicated to the evidence-based advancement of MSC exosome therapeutics. Our science is founded on more than 2 decades of investigation by the founder and her team at the Agency for Science, Technology and Research (A*STAR).

These investigations include different aspects of MSC exosomes such as their biogenesis [1], their cargo of lipids [2-4], proteins [3, 5-7] and nucleic acids[3, 8], their biochemical activities[9], therapeutic potency etc. [10-29].  

Our rigorous research has proven the efficacy of our MSC exosomes in combating various diseases across multiple pre-clinical models, including osteoarthritis, eczema and liver fibrosis amidst others. 

Crucially we achieved a significant milestone by successfully completing a phase one clinical trial in May 2022. This trial marks the world’s first utilization of an immortalised MSC cell line for exosome production.

WHAT SETS US APART

Clonal Immortalized Cell Line

A key obstacle in advancing MSC exosomes is the challenge in manufacturing consistently identical and potent exosomes. This is caused primarily by the prevalent use of primary MSCs which have a limited lifespan and an inherent clonal heterogeniety.  

Paracrine Therapeutics is able to acheive consistent and reproducible batch-to-batch manufacture through robust GMP-compliant SOPs and GMP-validated cell banks of immortalized cells. This ensures uninterrupted continuity and uniformity of MSC exosome producer cells, ensuring consistency in our MSC exosome products.

Our Founder, Dr Lim Sai Kiang, along with Dr Lai Ruenn Chai, are recognized for their scientific achievements in MSC exosome research and are credited with the discovery of MSC exosomes therapeutic effects back in 2008.

They have since emerged as key opinion leaders in this field, earning acclaim as Clarivate highly cited researchers for consective years 2021, 2022, and 2023, placing them among the top 0.1% globally. 

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References
  1. Lai, R.C., et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res, 2010. 4(3): p. 214-22.
  2. Arslan, F., et al., Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res, 2013. 10(3): p. 301-12.
  3. Charles, C.J., et al., Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model. Front Cardiovasc Med, 2020. 7: p. 601990.
  4. Tan, C.Y., et al., Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther, 2014. 5(3): p. 76.
  5. Zhang, B., et al., MSC-sEV Treatment Polarizes Pro-Fibrotic M2 Macrophages without Exacerbating Liver Fibrosis in NASH. Int J Mol Sci, 2023. 24(9).
  6. * Zhang, S., et al., Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage, 2016. 24(12): p. 2135-2140.
  7. Zhang, S., et al., MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials, 2018. 156: p. 16-27.
  8. Chew, J.R.J., et al., Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomater, 2019. 89: p. 252-264.
  9. Zhang, S., et al., MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials, 2019. 200: p. 35-47.
  10. Wong, K.L., et al., Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model. Arthroscopy, 2020. 36(8): p. 2215-2228 e2.
  11. Chuah, S.J., et al., Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing. Genes Dis, 2022. 9(4): p. 841-844.
  12. Zhang, B., et al., Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance. Biomolecules, 2023. 13(10).
  13. Zhang, B., et al., Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev, 2014. 23(11): p. 1233-44.
  14. * Zhang, B., et al., Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway. Cytotherapy, 2018. 20(5): p. 687-696.
  15. Zhang, B., et al., Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation. Int J Mol Sci, 2021. 22(2).
  16. Loh, J.T., et al., Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes. Cytotherapy, 2022. 24(7): p. 711-719.
  17. Lai, R.C., et al., A roadmap from research to clinical testing of mesenchymal stromal cell exosomes in the treatment of psoriasis. Cytotherapy, 2023. 25(8): p. 815-820.
  18. Accarie, A., et al., Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome. Stem Cell Res Ther, 2020. 11(1): p. 371.
  19. Loinard, C., et al., HuMSC-EV induce monocyte/macrophage mobilization to orchestrate neovascularization in wound healing process following radiation injury. Cell Death Discov, 2023. 9(1): p. 38.
  20. Dorronsoro, A., et al., Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging. Aging Cell, 2021. 20(4): p. e13337.

References

  1. Lai, R.C., R.W. Yeo, and S.K. Lim, Mesenchymal stem cell exosomes. Semin Cell Dev Biol, 2015. 40: p. 82-8.
  2. Tan, S.S., et al., Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. J Extracell Vesicles, 2013. 2.
  3. Lai, R.C., et al., MSC secretes at least 3 EV types each with a unique permutation of membrane lipid, protein and RNA. J Extracell Vesicles, 2016. 5: p. 29828.
  4. Lai, R.C. and S.K. Lim, Membrane lipids define small extracellular vesicle subtypes secreted by mesenchymal stromal cells. J Lipid Res, 2019. 60(2): p. 318-322.
  5. Lai, R.C., et al., Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome. Int J Proteomics, 2012. 2012: p. 971907.
  6. van Balkom, B.W.M., et al., Proteomic Signature of Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles. Proteomics, 2019. 19(1-2): p. e1800163.
  7. Toh, W.S., et al., MSC exosome works through a protein-based mechanism of action. Biochem Soc Trans, 2018. 46(4): p. 843-853.
  8. Chen, T.S., et al., Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res, 2010. 38(1): p. 215-24.
  9. Lai, R.C., et al., Mesenchymal Stem Cell Exosomes: The Future MSC-based Therapy?, in Mesenchymal Stem Cell Therapy, L.G. Chase and M.C. Vemuri, Editors. 2012, Humana Press.
  10. Lai, R.C., et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res, 2010. 4(3): p. 214-22.
  11. Arslan, F., et al., Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res, 2013. 10(3): p. 301-12.
  12. Charles, C.J., et al., Systemic Mesenchymal Stem Cell-Derived Exosomes Reduce Myocardial Infarct Size: Characterization With MRI in a Porcine Model. Front Cardiovasc Med, 2020. 7: p. 601990.
  13. Tan, C.Y., et al., Mesenchymal stem cell-derived exosomes promote hepatic regeneration in drug-induced liver injury models. Stem Cell Res Ther, 2014. 5(3): p. 76.
  14. Zhang, B., et al., MSC-sEV Treatment Polarizes Pro-Fibrotic M2 Macrophages without Exacerbating Liver Fibrosis in NASH. Int J Mol Sci, 2023. 24(9).
  15. * Zhang, S., et al., Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration. Osteoarthritis Cartilage, 2016. 24(12): p. 2135-2140.
  16. Zhang, S., et al., MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials, 2018. 156: p. 16-27.
  17. Chew, J.R.J., et al., Mesenchymal stem cell exosomes enhance periodontal ligament cell functions and promote periodontal regeneration. Acta Biomater, 2019. 89: p. 252-264.
  18. Zhang, S., et al., MSC exosomes alleviate temporomandibular joint osteoarthritis by attenuating inflammation and restoring matrix homeostasis. Biomaterials, 2019. 200: p. 35-47.
  19. Wong, K.L., et al., Intra-Articular Injections of Mesenchymal Stem Cell Exosomes and Hyaluronic Acid Improve Structural and Mechanical Properties of Repaired Cartilage in a Rabbit Model. Arthroscopy, 2020. 36(8): p. 2215-2228 e2.
  20. Chuah, S.J., et al., Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing. Genes Dis, 2022. 9(4): p. 841-844.
  21. Zhang, B., et al., Therapeutic Efficacy of Mesenchymal Stem/Stromal Cell Small Extracellular Vesicles in Alleviating Arthritic Progression by Restoring Macrophage Balance. Biomolecules, 2023. 13(10).
  22. Zhang, B., et al., Mesenchymal stem cells secrete immunologically active exosomes. Stem Cells Dev, 2014. 23(11): p. 1233-44.
  23. * Zhang, B., et al., Mesenchymal stromal cell exosome-enhanced regulatory T-cell production through an antigen-presenting cell-mediated pathway. Cytotherapy, 2018. 20(5): p. 687-696.
  24. Zhang, B., et al., Topical Application of Mesenchymal Stem Cell Exosomes Alleviates the Imiquimod Induced Psoriasis-Like Inflammation. Int J Mol Sci, 2021. 22(2).
  25. Loh, J.T., et al., Mechanism for the attenuation of neutrophil and complement hyperactivity by MSC exosomes. Cytotherapy, 2022. 24(7): p. 711-719.
  26. Lai, R.C., et al., A roadmap from research to clinical testing of mesenchymal stromal cell exosomes in the treatment of psoriasis. Cytotherapy, 2023. 25(8): p. 815-820.
  27. Accarie, A., et al., Extracellular vesicles derived from mesenchymal stromal cells mitigate intestinal toxicity in a mouse model of acute radiation syndrome. Stem Cell Res Ther, 2020. 11(1): p. 371.
  28. Loinard, C., et al., HuMSC-EV induce monocyte/macrophage mobilization to orchestrate neovascularization in wound healing process following radiation injury. Cell Death Discov, 2023. 9(1): p. 38.
  29. Dorronsoro, A., et al., Mesenchymal stem cell-derived extracellular vesicles reduce senescence and extend health span in mouse models of aging. Aging Cell, 2021. 20(4): p. e13337.