LAUSR

Background & Aim Most tissues in the body harbour adult tissue stem cells (SCs) – multipotent, quiescent cells, capable of self-renewal, proliferation and differentiation into mature cellular subtypes. With the discovery of the unique properties of stem cells and their regenerative capacity came the possibility of utilizing these cells for therapeutic purposes. While very promising, stem cell therapy is thwarted by the challenge of obtaining donor-derived SCs in numbers that are sufficient to support therapy development with in vitro expansion leading to premature aging, loss of stemness and a significantly decreased functional and regenerative capacity of these cells. To address this challenge and based on the scientific reports of delayed aging following exposures to low-dose ionizing radiation in vitro and in vivo, we decided to investigate the effects of low-dose radiation (LDR) on cord-blood derived mesenchymal stem and progenitor cells (MSC/MSPC) and endothelial colony forming cells (ECFC). Methods, Results & Conclusion In our study, young, passage 4 stem cells were acutely irradiated with 10, 50 and 100 mGy gamma rays. Both SC types were aged in culture and their proliferation was monitored using Incucyte. Aging was defined as a decline in cell proliferative capacity and function. MSC function was evaluated based on the extent of chondrogenic differentiation. ECFC function was assessed by migration capacity in a scratch wound assay. The results of this study demonstrated that in vitro cultured non-irradiated MSCs and ECFCs aged significantly with cell doubling time increasing ∼3.0 fold. However, all doses of LDR treatment at early passage provided lasting effects and delayed aging, represented by improved proliferative capacity of 1.5-2.2 fold. Similarly, chondrogenic differentiation of aged MSCs decreased ∼2 fold but was restored back to young cell control levels with 50 and 100 mGy treatment. Interestingly, a 10 mGy exposure led to 50% further improvement exceeding the levels for young controls. The migratory capacity of aged ECFCs decreased ∼2 fold in comparison to young cells and was improved by ∼30% with LDR exposure. Thus, this report provides the first evidence of delayed aging and improved functional capacity of in vitro expanded mesenchymal and endothelial stem cells.