Chapel, A Semont, N Mathieu, C Linard, L Douay, NC Gorin, M Mothy,JM Simmon, H Rouard, JJ Lataillade, J Voswinkel, and M Benderitter
Institute of Radiological Protection and Nuclear Safety, France Saint Antoine Hospital APHP and UPMC University, France Pitie-Salpetriere University Hospital, France Percy Military Hospital, France
Posters & Accepted Abstracts: J Biomedical Sci
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. Our group has demonstrated in preclinical animal models that systemic MSC injection is a promise approach for the medical management of gastrointestinal disorder after irradiation. We have shown that MSC migrate to damaged tissues and restore gut functions after irradiation.
The clinical status of four first patients suffering from severe pelvic side effects resulting from an over-dosage was improved following MSC injection in a compassional situation. A quantity of 2x106 - 6x106 MSC /kg were infused intravenously to the patients. Pain, hemorrhage, frequency of diarrheas and fistulisation as well as the lymphocyte subsets in peripheral blood were evaluated before MSC therapy and during the follow-up. Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. In one patient pain reappeared after 6 months and again substantially responded on a second MSC infusion. A beginning fistulisation process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. The frequency of painful diarrhea diminished from an average of 6/d to 3/d after the first and 2/d after the 2nd MSC injection in one patient. In all patients, prostate cancer remained in stable complete remission. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response in refractory irradiation-induced colitis. No toxicity occurred.
MSC therapy was safe and effective on pain, diarrhea, haemorrhage, inflammation, fibrosis and limited fistulisation. For patients with refractory chronic inflammatory and fistulising bowel diseases, systemic MSC injections represent a safe option for salvage therapy. A clinical phase II trial will start in 2017