2. Academic Validation
  3. RSPO1, a potent inducer of pancreatic β cell neogenesis

RSPO1, a potent inducer of pancreatic β cell neogenesis

  • Cell Rep Med. 2025 May 20;6(5):102126. doi: 10.1016/j.xcrm.2025.102126.
Serena Silvano 1,  Tiziana Napolitano 1,  Magali Plaisant 1,  Anette Sousa-De-Veiga 2,  Hugo Fofo 2,  Chaïma Ayachi 2,  Benoit Allegrini 2,  Samah Rekima 2,  Estelle Pichery 3,  Jérôme Becam 4,  Valentin Lepage 2,  Caroline Treins 1,  Laura Etasse 1,  Loan Tran 1,  Julien Thévenet 5,  Gianni Pasquetti 5,  Julie Kerr-Conte 5,  François Pattou 5,  Paolo Botti 1,  Arduino Arduini 1,  Jacques Mizrahi 1,  Benjamin Charles 1,  Patrick Collombat 6
Affiliations

Affiliations

  • 1 DiogenX, 180 Avenue du Prado, 13008 Marseille, France.
  • 2 University Nice Cote D'Azur, Inserm, CNRS, iBV, 06100 Nice, France; iBV, Institut de Biologie Valrose, University Nice Sophia Antipolis, Centre de Biochimie, Parc Valrose, 28, Avenue Valrose, 06108 Nice Cedex 2, France.
  • 3 Université Côte d'Azur, Inserm, C3M, Nice, France.
  • 4 Aix-Marseille Université, CNRS, Laboratoire de Chimie Bactérienne, UMR 7283, Institut de Microbiologie de la Méditerranée, 31 Chemin Joseph Aiguier, 13009 Marseille, France.
  • 5 University Lille, Inserm, CHU Lille, U1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, EGID, 59000 Lille, France.
  • 6 DiogenX, 180 Avenue du Prado, 13008 Marseille, France; University Nice Cote D'Azur, Inserm, CNRS, iBV, 06100 Nice, France; iBV, Institut de Biologie Valrose, University Nice Sophia Antipolis, Centre de Biochimie, Parc Valrose, 28, Avenue Valrose, 06108 Nice Cedex 2, France. Electronic address: collombat@unice.fr.
PMID: 40339569 DOI: 10.1016/j.xcrm.2025.102126
Abstract

Inducing the neogenesis of pancreatic insulin-producing β cells holds great promise for diabetes research. However, non-toxic compounds with such activities remain to be discovered. Herein, we report the identification of RSPO1, a key agonist of the Wnt/β-catenin pathway, as an inducer of β cell replication. Specifically, we provide evidence that RSPO1 promotes a significant increase in β cell neogenesis in vitro, ex vivo, and in vivo. Importantly, RSPO1 administration is sufficient to activate Wnt/β-catenin signaling in β cells and counter chemically induced or autoimmune-mediated diabetes. Similarly, an optimized analog of RSPO1, allowing for weekly administration, also prevents diabetes in vivo. Lastly, the treatment of transplanted human islets with RSPO1 induces a significant 2.78-fold increase in human β cell numbers in only 60 days, these cells being functional. Such activities of RSPO1 to promote β cell neogenesis could therefore represent an unprecedented hope in the continued search for diabetes alternative therapies.

Keywords

Rspo1; Wnt/β-catenin signaling; diabetes; endocrine pancreas; islets of Langerhans; β cell replication.

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