The stromal vascular fraction mitigates radiation-induced gastrointestinal syndrome in mice

Lydia Bensemmane,Fabien Milliat,Christelle Demarquay,Bernard Le Guen,Claire Squiban,Christine Linard,Marc Benderitter,Noëlle Mathieu

doi:10.1186/s13287-021-02373-y

Lydia Bensemmane, Fabien Milliat + Show 6 more

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https://doi.org/10.1186/s13287-021-02373-y

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Journal: Stem cell research & therapy	Publication Date: May 29, 2021
Citations: 9	License type: open-access

Abstract

BackgroundThe intestine is particularly sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. There is an urgent need for effective and rapid therapeutic countermeasures. The stromal vascular fraction (SVF) derived from adipose tissue is an easily accessible source of cells with angiogenic, anti-inflammatory and regenerative properties. We studied the therapeutic impact of SVF and its action on the intestinal stem cell compartment.MethodsMice exposed to the abdominal radiation (18 Gy) received a single intravenous injection of stromal vascular fraction (SVF) (2.5 × 106 cells), obtained by enzymatic digestion of inguinal fat tissue, on the day of irradiation. Mortality was evaluated as well as intestinal regeneration by histological analyses and absorption function.ResultsThe SVF treatment limited the weight loss of the mice and inhibited the intestinal permeability and mortality after abdominal irradiation. Histological analyses showed that SVF treatment stimulated the regeneration of the epithelium by promoting numerous enlarged hyperproliferative zones. SVF restored CD24+/lysozyme− and Paneth cell populations in the ISC compartment with the presence of Paneth Ki67+ cells. SVF has an anti-inflammatory effect by repressing pro-inflammatory cytokines, increasing M2 macrophages in the ileum and anti-inflammatory monocyte subtypes CD11b+Ly6clowCX3CR1high in the spleen.ConclusionsThrough the pleiotropic effects that contribute to limiting radiation-induced lethality, SVF opens up attractive prospects for the treatment of emergency GIS.

Highlights

The intestine is sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival
We evaluated the therapeutic efficacy of stromal vascular fraction (SVF) in a GIS model and examined the impact of SVF on the niche compartment of intestinal stem cells and the impact on the inflammatory process
The dose that induces a GIS was established on the basis of the number of regenerating crypts forming microcolonies 3.5 days after irradiation

Summary

Introduction

The intestine is sensitive to moderate-high radiation dose and the development of gastrointestinal syndrome (GIS) leads to the rapid loss of intestinal mucosal integrity, resulting in bacterial infiltration, sepsis that comprise patient survival. Irradiation of large volumes at medium to high radiation doses has serious effects on normal, fast-renewing tissues, and all these effects are Bensemmane et al Stem Cell Research & Therapy (2021) 12:309. Normal homeostasis of the intestinal epithelium is maintained by a complex cell replacement process. This renewal is initiated by intestinal stem cells (ISCs), notably the Lgr5+ cells located at the base of the crypts [1]. These stem cells divide, migrate and become Lgr progenitors or transit-amplifying progenitor (TA) cells committed to differentiation. In addition to their antimicrobial role, these cells have played an essential niche role in supporting Lgr5+ cells, both through cell-cell contact and by secreting the factors necessary to maintain the gut stem cell niche [2]

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