Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Agonist (P1) Antibody Converts Stem Cells into Migrating Beta-Like Cells in Pancreatic Islets

  • Eun Ji Lee (Department of Biological Sciences and Biotechnology, Hannam University) ;
  • Seung-Ho Baek (Research Center for Bio-based Chemistry, Korea Research Institute of Chemical Technology (KRICT)) ;
  • Chi Hun Song (Department of Biological Sciences and Biotechnology, Hannam University) ;
  • Yong Hwan Choi (Department of Biological Sciences and Biotechnology, Hannam University) ;
  • Kyung Ho Han (Department of Biological Sciences and Biotechnology, Hannam University)
  • Received : 2022.09.20
  • Accepted : 2022.10.17
  • Published : 2022.12.28
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Abstract

Tissue regeneration is the ultimate treatment for many degenerative diseases, however, repair and regeneration of damaged organs or tissues remains a challenge. Previously, we showed that B1 Ab and H3 Ab induce stem cells to differentiate into microglia and brown adipocyte-like cells, while trafficking to the brain and heart, respectively. Here, we present data showing that another selected agonist antibody, P1 antibody, induces the migration of cells to the pancreatic islets and differentiates human stem cells into beta-like cells. Interestingly, our results suggest the purified P1 Ab induces beta-like cells from fresh, human CD34+ hematopoietic stem cells and mouse bone marrow. In addition, stem cells with P1 Ab bound to expressed periostin (POSTN), an extracellular matrix protein that regulates tissue remodeling, selectively migrate to mouse pancreatic islets. Thus, these results confirm that our in vivo selection system can be used to identify antibodies from our library which are capable of inducing stem cell differentiation and cell migration to select tissues for the purpose of regenerating and remodeling damaged organ systems.

Keywords

Acknowledgement

This work was supported by the 2021 Hannam University Research Fund. We thank Britni M. Arlian (Scripps Research) and Hee-Sook Jun (Gachon University) for helpful discussions and advice.

References

  1. Han KH, Gonzalez-Quintial R, Peng Y, Baccala R, Theofilopoulos AN, Lerner RA. 2016. An agonist antibody that blocks autoimmunity by inducing anti-inflammatory macrophages. FASEB J. 30: 738-747. https://doi.org/10.1096/fj.15-281329
  2. Han KH, Arlian BM, Macauley MS, Paulson JC, Lerner RA. 2018. Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid beta. Proc. Natl. Acad. Sci. USA 115: E372-E381.
  3. Han KH, Arlian BM, Lin CW, Jin HY, Kang GH, Lee S, et al. 2020. Agonist antibody converts stem cells into migrating brown adipocyte-like cells in heart. Cells 9: 256.
  4. Kang S, Park HW, Han KH. 2022. Antibodies regulate dual-function enzyme IYD to induce functional synergy between metabolism and thermogenesis. Int. J. Mol. Sci. 23: 7834.
  5. Walker JT, McLeod K, Kim S, Conway SJ, Hamilton DW. 2016. Periostin as a multifunctional modulator of the wound healing response. Cell Tissue Res. 365: 453-465. https://doi.org/10.1007/s00441-016-2426-6
  6. Wu Z, Dai W, Wang P, Zhang X, Tang Y, Liu L, et al. 2018. Periostin promotes migration, proliferation, and differentiation of human periodontal ligament mesenchymal stem cells. Connect. Tissue Res. 59: 108-119. https://doi.org/10.1080/03008207.2017.1306060
  7. Xie J, Zhang H, Yea K, Lerner RA. 2013. Autocrine signaling based selection of combinatorial antibodies that transdifferentiate human stem cells. Proc. Natl. Acad. Sci. USA 110: 8099-8104. https://doi.org/10.1073/pnas.1306263110
  8. Zhang H, Yea K, Xie J, Ruiz D, Wilson IA, Lerner RA. 2013. Selecting agonists from single cells infected with combinatorial antibody libraries. Chem. Biol. 20: 734-741. https://doi.org/10.1016/j.chembiol.2013.04.012
  9. Diaferia GR, Jimenez-Caliani AJ, Ranjitkar P, Yang W, Hardiman G, Rhodes CJ, et al. 2013. β1 integrin is a crucial regulator of pancreatic beta-cell expansion. Development 140: 3360-3372. https://doi.org/10.1242/dev.098533
  10. Duchamp de Lageneste O, Colnot C. 2019. Periostin in bone regeneration. Adv. Exp. Med. Biol. 1132: 49-61. https://doi.org/10.1007/978-981-13-6657-4_6
  11. Izuhara K, Nunomura S, Nanri Y, Ono J, Takai M, Kawaguchi A. 2019. Periostin: An emerging biomarker for allergic diseases. Allergy 74: 2116-2128. https://doi.org/10.1111/all.13814
  12. Kormann R, Kavvadas P, Placier S, Vandermeersch S, Dorison A, Dussaule JC, et al. 2020. Periostin promotes cell proliferation and macrophage polarization to drive repair after AKI. J. Am. Soc. Nephrol. 31: 85-100. https://doi.org/10.1681/ASN.2019020113
  13. Sonnenberg-Riethmacher E, Miehe M, Riethmacher D. 2021. Periostin in allergy and inflammation. Front. Immunol. 12: 722170.
  14. Nie X, Shen C, Tan J, Wu Z, Wang W, Chen Y, et al. 2020. Periostin: A Potential therapeutic target for pulmonary hypertension? Circ. Res. 127: 1138-1152. https://doi.org/10.1161/CIRCRESAHA.120.316943
  15. Wang Z, An J, Zhu D, Chen H, Lin A, Kang J, et al. 2022. Periostin: an emerging activator of multiple signaling pathways. J. Cell Commun. Signal. 16: 515-530.
  16. Borowiak M. 2010. The new generation of beta-cells: replication, stem cell differentiation, and the role of small molecules. Rev. Diabet. Stud. 7: 93-104. https://doi.org/10.1900/RDS.2010.7.93
  17. Basile G, Kulkarni RN, Morgan NG. 2019. How, When, and where do human beta-cells regenerate? Curr. Diab Rep. 19: 48.
  18. Ji Z, Lu M, Xie H, Yuan H, Chen Q. 2022. β cell regeneration and novel strategies for treatment of diabetes (Review). Biomed Rep. 17: 72.
  19. Kerper N, Ashe S, Hebrok M. 2022. Pancreatic β-cell development and regeneration. Cold Spring Harb. Perspect. Biol. 14: a040741.
  20. Liesveld JL, Sharma N, Aljitawi OS. 2020. Stem cell homing: From physiology to therapeutics. Stem Cells 38: 1241-1253. https://doi.org/10.1002/stem.3242
  21. Yuan M, Hu X, Yao L, Jiang Y, Li L. 2022. Mesenchymal stem cell homing to improve therapeutic efficacy in liver disease. Stem Cell Res. Ther. 13: 179.
  22. Zhu D, Zhou W, Wang Z, Wang Y, Liu M, Zhang G, et al. 2021. Periostin: an emerging molecule with a potential role in spinal degenerative diseases. Front. Med (Lausanne) 8: 694800.
  23. Cobo T, Viloria CG, Solares L, Fontanil T, Gonzalez-Chamorro E, De Carlos F, et al. 2016. Role of periostin in adhesion and migration of bone remodeling cells. PLoS One 11: e0147837.
  24. Rosselli-Murai LK, Almeida LO, Zagni C, Galindo-Moreno P, Padial-Molina M, Volk SL, et al. 2013. Periostin responds to mechanical stress and tension by activating the MTOR signaling pathway. PLoS One 8: e83580.
  25. Ouanouki A, Lamy S, Annabi B. 2018. Periostin, a signal transduction intermediate in TGF-beta-induced EMT in U-87MG human glioblastoma cells, and its inhibition by anthocyanidins. Oncotarget 9: 22023-22037. https://doi.org/10.18632/oncotarget.25153