Multipotent mesenchymal stem cell grafting to treat cutaneous radiation syndrome: development of a new minipig model
Received 13 January 2010; received in revised form 10 June 2010; accepted 21 June 2010. published online 28 June 2010. Uncorrected Proof
Objective
Cutaneous radiation syndrome (CRS) is the delayed consequence of localized skin exposure to high doses of ionizing radiation. Recent grafting of three ionizing radiation−burned patients has suggested the benefit of local bone marrow mesenchymal stem cell (MSC) injection in favor of wound healing and pain control. Here, we have developed a new minipig model of severe CRS to study underlying mechanisms of this cell therapy approach.
Materials and Methods
Göttingen minipigs were locally irradiated using a 60Co gamma source as follows: ungrafted 50 and 60 Gy (n = 4) and grafted 50 and 60 Gy (n = 3). Bone marrow MSCs were cultured in minimum essential medium with 10% fetal calf serum and basic fibroblast growth factor (2 ng·mL−1). Autologous MSCs were intradermally injected twice or three times from days 27 to 96 (range, 99−128.5 × 106 MSCs per injection).
Results
All animals exhibited a clinical evolution similar to humans after a latency phase of several weeks, including early erythema, hair loss, and dry/moist desquamation followed by necrosis during 81 to 222 days post−ionizing radiation. Skin damage in higher exposed animals appeared slightly earlier. Immunohistology revealed severe skin damage in all animals and rhabdomyolysis in the muscle tissue below the entry area, with the latter being more severe in controls. In grafted animals, MSCs led to local accumulation of lymphocytes at the dermis/subcutis border and improved vascularization.
Conclusion
This study establishes a new minipig model that is close to human and allows development of stem cell therapy strategies that can be applied in treatment of human radiation burns.
aIRBA-antenne La Tronche-CRSSA, La Tronche, France
bInstitut für Radiobiologie der Bundeswehr in Verbindung mit der Universität Ulm, München, Germany
Offprint requests to: Michel Drouet, Ph.D., M.D., IRBA-antenne La Tronche-CRSSA, 24 Avenue des Maquis du Grésivaudan, La Tronche 38702, France
ABSTRACT