New insights for pelvic radiation disease treatment: Multipotent stromal cell is a promise mainstay treatment for the restoration of abdominopelvic severe chronic damages induced by radiotherapy

Abstract

Radiotherapy may induce irreversible damage on healthy tissues surrounding the tumor. It has been reported that the majority of patients receiving pelvic radiation therapy show early or late tissue reactions of graded severity as radiotherapy affects not only the targeted tumor cells but also the surrounding healthy tissues. The late adverse effects of pelvic radiotherapy concern 5% to 10% of them, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Although no pharmacologic interventions have yet been proven to efficiently mitigate radiotherapy severe side effects, few preclinical researches show the potential of combined and sequential pharmacological treatments to prevent the onset of tissue damage. Our group has demonstrated in preclinical animal models that systemic mesenchymal stromal cell (MSC) injection is a promising approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSCs migrate to damaged tissues and restore gut functions after irradiation. We carefully studied side effects of stem cell injection for further application in patients. We have shown that clinical status of four patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compationnal situation.

Keywords: Cell therapy; Clinical trial; Irradiation; Mesenchymal stem cells; Multipotent stromal cells; Radiotherapy; Stem cells.

Figure 1

Clinical trials to treat consequences of radiotherapy. Clinical and pre-clinical use of stem cells to treat toxic side effects induced by radiotherapy on healthy tissue of radio-sensitive patients. Pathologies treated are (left side) osteonecrosis, xerostomia, atherosclerosis, cardiac attack, breast cancer, liver disease, pelvic radiation disease, radiodermatitis and bone marrow aplasia. Targeted organs (brain, salivary glands, mandibles, skin, liver, heart and rectum/bladder, bone marrow) are mentioned on the left side. On the right side, stem cells are isolated from several tissue sources, expanded in vitro, then injected locally (i loc) or intravenously (iv). Stem cells from bone marrow and adipose tissues are used in clinic. Other sources of stem cells (neural stem cell, salivary gland stem cell, hepatocyte and embryonic stem cell) are only used in animal models (pre-clinical use).