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Sci Rep. 2019 Jan 17;9(1):164. doi: 10.1038/s41598-018-36631-6.

Heparan Sulfate Mimetics: A New Way to Optimize Therapeutic Effects of Hydrogel-Embedded Mesenchymal Stromal Cells in Colonic Radiation-Induced Damage.

Author information

1
IRSN, Institut de Radioprotection et de Sûreté Nucléaire, PSE-SANTE, SERAMED, LRMed, 31 avenue de la division Leclerc, 92262, Fontenay-aux-Roses, France.
2
INSERM, Institut National de la Santé et de la Recherche Médicale, U1229, Regenerative Medicine and Skeleton (RMeS), Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042, Nantes, France.
3
Université de Nantes, Regenerative Medicine and Squeleton (RMeS), Faculté de Chirurgie Dentaire, 1 Place Alexis Ricordeau, 44042, Nantes, France.
4
Centre Hospitalier Universitaire de Nantes, Pôle Hospitalo-Universitaire 4 (OTONN), 1 Place Alexis Ricordeau, 44042, Nantes, France.
5
Société OTR3 (Organes, Tissus, Régénération, Réparation, Remplacement), 4 Rue Française, 75001, Paris, France.
6
Université Paris-Est Créteil, Laboratoire de recherche sur la Croissance Cellulaire, Réparation, et Régénération Tissulaire, Faculté des Sciences, Université Paris-Est Créteil, 61 Ave du Gal de Gaulle, 94000, Créteil, France.
7
IRSN, Institut de Radioprotection et de Sûreté Nucléaire, PSE-SANTE, SERAMED, LRMed, 31 avenue de la division Leclerc, 92262, Fontenay-aux-Roses, France. noelle.mathieu@irsn.fr.

Abstract

Clinical expression of gastrointestinal radiation toxicity on non-cancerous tissue could be very life threatening and clinicians must deal increasingly with the management of late side effects of radiotherapy. Cell therapy, in particular mesenchymal stromal cell (MSC) therapy, has shown promising results in numerous preclinical animal studies and thus has emerged as a new hope for patient refractory to current treatments. However, many stem cell clinical trials do not confer any beneficial effect suggesting a real need to accelerate research towards the successful clinical application of stem cell therapy. In this study, we propose a new concept to improve the procedure of MSC-based treatment for greater efficacy and clinical translatability. We demonstrated that heparan sulfate mimetic (HS-m) injections that restore the extracellular matrix network and enhance the biological activity of growth factors, associated with local injection of MSC protected in a hydrogel, that increase cell engraftment and cell survival, improve the therapeutic benefit of MSC treatment in two animal models relevant of the human pathology. For the first time, a decrease of the injury score in the ulcerated area was observed with this combined treatment. We also demonstrated that the combined treatment favored the epithelial regenerative process. In this study, we identified a new way, clinically applicable, to optimize stem-cell therapy and could be proposed to patients suffering from severe colonic defect after radiotherapy.

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