A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic radiation-induced damage

Lara Moussa (1, 2) , Girish Pattappa (1) , Bastien Doix (2) , Sarra-Louiza Benselama (2) , Christelle Demarquay (2) , Marc Benderitter (2) , Alexandra Sémont (2) , Radia Tamarat (2) , Jérôme Guicheux (1, 3) , Pierre Weiss (1, 3) , Gildas Réthoré (1, 3) , Noëlle Mathieu (2)

1 LIOAD - Laboratoire d'ingénierie osteo-articulaire et dentaire
2 IRSN/PRP-HOM/SRBE/LR2I - Laboratoire de recherche en régénération des tissus sains irradiés
3 Pôle hospitalo-universitaire PHU4 - OTONN - Ostéo-articulaire - Tête et cou - Odontologie - Neurochirurgie - Neurotraumatologie [CHU Nantes]

Healthy tissues surrounding abdomino-pelvic tumours can be impaired by radiotherapy, leading to chronic gastrointestinal complications with substantial mortality. Adipose-derived Mesenchymal Stro-mal Cells (Ad-MSCs) represent a promising strategy to reduce intestinal lesions. However, systemic administration of Ad-MSCs results in low cell engraftment within the injured tissue. Biomaterials, able to encapsulate and withstand Ad-MSCs, can overcome these limitations. A silanized hydroxypropylmethyl cellulose (Si-HPMC) hydrogel has been designed and characterized for injectable cell delivery using the operative catheter of a colonoscope. We demonstrated that hydrogel loaded-Ad-MSCs were viable, able to secrete trophic factors and responsive to the inflammatory environment. In a rat model of radiation-induced severe colonic damage, Ad-MSC þ Si-HPMC improve colonic epithelial structure and hyper-permeability compared with Ad-MSCs injected intravenously or locally. This therapeutic benefit is associated with greater engraftment of Si-HPMC-embedded Ad-MSCs in the irradiated colonic mucosa. Moreover, macrophage infiltration near the injection site was less pronounced when Ad-MSCs were embedded in the hydrogel. Si-HPMC induces modulation of chemoattractant secretion by Ad-MSCs that could contribute to the decrease in macrophage infiltrate. Si-HPMC is suitable for cell delivery by co-lonoscopy and induces protection of Ad-MSCs in the tissue potentiating their therapeutic effect and could be proposed to patients suffering from colon diseases.

Mots clés: Colorectal irradiation; Mesenchymal stromal cells; Colonic permeability; Hydrogel; Regenerative medicine; Injection through colonoscopy

Domaines: Rhumatologie et système ostéo-articulaire; Gériatrie et gérontologie

Lara Moussa, Girish Pattappa, Bastien Doix, Sarra-Louiza Benselama, Christelle Demarquay, et al.. A biomaterial-assisted mesenchymal stromal cell therapy alleviates colonic radiation-induced damage. Biomaterials, 2017, 115, pp.40 - 52. ⟨10.1016/j.biomaterials.2016.11.017⟩. ⟨inserm-01845123⟩