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

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.
Complete list of metadatas

Cited literature [57 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-01985739
Contributor : Valérie Pecqueret <>
Submitted on : Friday, January 18, 2019 - 11:26:00 AM
Last modification on : Friday, October 4, 2019 - 1:39:45 AM

File

s41598-018-36631-6.pdf
Publisher files allowed on an open archive

Identifiers

Collections

Citation

Lara Moussa, Christelle Demarquay, Gildas Réthoré, Mohamed Amine Benadjaoud, Fernando Siñeriz, et al.. Heparan Sulfate Mimetics: A New Way to Optimize Therapeutic Effects of Hydrogel-Embedded Mesenchymal Stromal Cells in Colonic Radiation-Induced Damage. Scientific Reports, Nature Publishing Group, 2019, 9 (1), ⟨10.1038/s41598-018-36631-6⟩. ⟨inserm-01985739⟩

Share

Metrics

Record views

391

Files downloads

199