Vascular Stromal Fraction for the treatment of the radiation induced gastro intestinal syndrome
Thesis: Exposure to ionizing radiation following an irradiation accident or a terrorism act can affect both civilians and military personnel. This exposure can have serious consequences on the health of exposed persons and potentially impact a large number of people. In humans, doses higher than 6 Gy over a large volume mainly induce bone marrow destruction and gastrointestinal lesions, leading to diarrhea, dehydration, septicemia and intestinal hemorrhage with mortality within 10 to 15 days after exposure. This lethal syndrome induces the loss of intestinal stem cells (ISC) and thus, impairs epithelial regeneration. The damaged intestinal epithelium results in a breakdown of the barrier, allowing systemic influx of bacterial pathogens. These gastrointestinal symptoms are collectively known as radiation-induced gastrointestinal syndrome (GIS). Although life-threatening, GIS is still facing a therapeutic wall and its management is only symptomatic. Moreover, the time of intervention for the treatment of irradiated persons is primordial and there is a huge need for effective and rapid therapeutic measures. Treatment with products derived from adipose tissue and more particularly the stromal-vascular fraction (SVF) is compatible with emergency treatment (can be prepared close to the operating room and without cell culture). The potential impact of this study will be important for the medical and rapid management of irradiated persons with a GIS. The objective of this thesis is to identify cellular targets of SVF treatment in an irradiation-induced intestinal stem cell deficient environment. The second objective is to evaluate the role and importance of host monocytes cells and the interaction between the host immunity and the stroma-intestinal stem cell for intestinal regeneration in mice. The first step is focused on the evaluation of intestinal cells targeted by SVF treatment of IGS. The second step will evaluate the role of monocytes/macrophages in GIS and their involvement in the therapeutic effects induced by SVF. This study demonstrated a direct effect of SVF on the stem cell compartment and that the cooperation between the SVF monocyte and the host monocyte is necessary for SVF to be effective in GIS.
Keywords
- Intestine
- Stromal vascular fraction
- Stem cell
- Cell therapy
- Accident
- Irradiation
Issuing body(s)
- Sorbonne Université
Date of defense
- 11/05/2023
Thesis director(s)
- Christine Linard
- Xavier Treton
URL of the HAL notice
Version
- 1