**2. Treatment of Radiation Lesions with Stem Cells**

Radiation lesions is amenable to treatment by methods that result in repairing or regeneration of the damaged tissue. In fact, stem cell transplantation in medical practice is not new and have been used for decades in bone marrow transplantation [4].

Stem cell treatment of radiation damage is based on the assumption that the transplanted cells integrate with the damaged host tissue to replace the damaged/lost cells or stimulate the host cells to prevent the damage or regenerate the damaged tissue. The later will obviously be more efficient before establishment of the radiation damage. Transplanting the stem cells before the full establishment of radiation lesion can prevent the development of radiation damage or shorten the duration of the manifestation of the lesion.

Bone marrow transplantation has been successfully used in the treatment of leukaemia, lymphoma, and certain types of anaemia procedures. Initial efforts in this field were directed towards transplantation of pre-differentiated stem cells and a good example of this is bone marrow transplantation that started as early as 1951 with the work of Lorenz [5] who found that infusion of the spleen or marrow cells could protect the irradiated mice. Bone marrow transplantation is based on allogenic use of stem cells. Whole marrow or stem cells of the marrow are extracted from a donor and transplanted to the host to

reconstruct the haemopoietic tissues of cancer patients. The patient, prior to bone-marrow transplantation, is myeloablated by radiation or chemotherapy. The process of bone marrow transplantation is reviewed by [4].

Later, non-tissue specific or naive stem cells were transplanted on the basis of the opinion that the niche, or local microenvironment, consisting of surrounding cells, will define the fate of the transplanted cells and direct the administered stem cells to lodge into target tissue and differentiate into the required cells to restore structural and functional deficits.

In this article, a number of papers indicating the application of stem cells in the treatment of radiation-induced lesions are reviewed. It is also argued that the beneficial effect of transplanted stem cells in irradiated bodies is not necessarily due to the lodging of the transplanted stem cells in the irradiated tissue to replace the lost/damaged cells. It is suggested that perhaps the result is by paracrine effect; i.e., transplanted stem cells secrete bioactive substances that are capable of stimulating the host cells to reproduce and repair the damaged tissue. This means that the transplanted stem cells, besides integrating in the structure of damaged tissues, secrete biologically active factors, mainly in the form of extracellular vesicles, such as exosomes and microvesicles, that stimulate and mobilise the endogenous stem cells to repair the damage. Recently, it was shown by many researchers including ourselves, that the effect of stem cells is exerted in a paracrine fashion [6–8]. Transplanted stem cells, by integration with the host tissue, mobilisation of endogenous stem cells, or a combination of both mechanisms, result in functional and structural improvements of injured tissues. For a review on extracellular vesicles, see [9,10].
