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.

Effects of human amnion–derived mesenchymal stromal cell transplantation in rats with radiation proctitis

“…Considering that FM is generally treated as medical waste and can be obtained without any invasive procedure, human AMSC transplantation may be a therapeutic strategy for the treatment of radiation proctitis. A clinical trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdomino-pelvic complications has been initiated in 2015 [46].…”

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

“…Knockdown experiments in IL-6 −/− mice showed a partial loss of the stem cells' ability to regenerate irradiated intestinal epithelium [62]. The first reports of patients treated with MSCs for severe radiation-induced intestinal side effects on the grounds of compassionate use demonstrated improvements in mucosal inflammation and hemorrhages, and a clinical trial has been proposed to further elucidate the usage of MSCs for radiation-induced intestinal damage [47,54].…”

“…It is estimated that between 30,000 and 50,000 patients develop severe radiation-associated intestinal complications worldwide every year [54], with no causative therapy available. The effects of MSCs on irradiated bowel tissues have been studied both in animal models and in patients on the grounds of compassionate use.…”

Long-term quantitative bio-distribution and side effects of human mesenchymal stem cells (hMSCs) engraftment in NOD/SCID mice following irradiation

“…Clinical data support the long-term safety of MSCs. Furthermore the followup of patients after cell therapy treatment after-radiotherapy for breast [24], bladder, or prostate cancers [25] has never revealed side effects over a long-time period. A methodical review of clinical trials examined the safety of MSCs using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (to June 2011).…”