Mesenchymal stem cells show radioresistance in vivo

Abstract

Irradiation impacts on the viability and differentiation capacity of tissue-borne mesenchymal stem cells (MSC), which play a pivotal role in bone regeneration. As a consequence of radiotherapy, bones may develop osteoradionecrosis. When irradiating human bone-derived MSC in vitro with increasing doses, the cells’ self-renewal capabilities were greatly reduced. Mitotically stalled cells were still capable of differentiating into osteoblasts and pre-adipocytes. As a large animal model comparable to the clinical situation, pig mandibles were subjected to fractionized radiation of 2 χ 9 Gy within 1 week. This treatment mimics that of a standardized clinical treatment regimen of head and neck cancer patients irradiated 30 χ 2 Gy. In the pig model, fractures which had been irradiated, showed delayed osseous healing. When isolating MSC at different time points post-irradiation, no significant changes regarding proliferation capacity and osteogenic differentiation potential became apparent. Therefore, pig mandibles were irradiated with a single dose of either 9 or 18 Gy in vivo, and MSC were isolated immediately afterwards. No significant differences between the untreated and 9 Gy irradiated bone with respect to proliferation and osteogenic differentiation were unveiled. Yet, cells isolated from 18 Gy irradiated specimens exhibited a reduced osteogenic differentiation capacity, and during the first 2 weeks proliferation rates were greatly diminished. Thereafter, cells recovered and showed normal proliferation behaviour. These findings imply that MSC can effectively cope with irradiation up to high doses in vivo. This finding should thus be implemented in future therapeutic concepts to protect regenerating tissue from radiation consequences.

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis

“…These findings signify the higher alertness and readiness of the DNA damage response machinery after RT exposure. These same mechanisms have been reported to be responsible for bmMSCs RT resistance [71,95,104,106,184,190].…”

“…These mechanisms includes: rapid formation of -H2AX for robust DSBs repair activation, time efficient G2/M arrest activation, competent DSBs repair, low IR-induced apoptotic response, stimulated expression of DNA damage repair-related genes, significantly high expression of the major player proteins in different IR-induced DNA damage repair pathways including HRR, NHEJR and other pathways; namely, DNAPKcs, RAD-51 p-ATM, CHEK2 and others, and activated the anti-oxidant machinery [91,95,96,184,189]. Even more, one study suggested such radioresistance of bone marrow-derived MSCs in-vivo [190]. Until now, to our knowledge, no studies have investigated the radiosensitivity/resistance of MSCs from adipose tissue origin.…”

Platelet factor 4 protects bone marrow mesenchymal stem cells from acute radiation injury

“…Single-cell suspension was obtained by passing through an 18-gauge needle and filtered with a nylon membrane, followed by erythrolysis in buffered 0.14-M NH 4 Cl. Cells were cultured in L-glutamine Dulbecco's minimum essential medium (LDMEM; Gibco®, Life Technologies Ltd, Grand Island, NY) containing 15% foetal bovine serum (FBS; Gibco) in a humidified atmosphere of 5% CO 2 at 37°C.…”

“…3 Since HSPCs are more sensitive to radiation, mesenchymal stem cells (MSCs) luckily have an intrinsic radiation-resistant phenotype. 4,5 Although effective radiation countermeasure approaches were initiated six decades ago, very few have unanimous endorsement by health professionals. Radiation protectors [such as WR-2721, Toll-like receptor ligands, flavonoids, Ex-RAD® (Onconova Therapeutics Inc., Newton, PA) and vitamin E] are prophylactic agents that are administered before exposure to prevent radiation-induced cellular and molecular damage.…”

X-ray radiation effect of C-arm on adipose tissue-mesenchymal stem cell viability and population doubling time

“…Cell endurance to irradiation is affected by the ability to produce antioxidants and the ability to repair DNA damage. 22 There are two mechanisms of DNA repair: non-homologous end joining (NHEJ) and homologous recombination (HR). The NHEJ has six components: Ku70, Ku80, DNA-PK, XRCC4, DNA ligase IV (LigIV), and XRCC4-like factor (XLF).…”