Therapeutic Potential of Mesenchymal Stromal Cells and Extracellular Vesicles in the Treatment of Radiation Lesions-A Review.

Ionising radiation-induced normal tissue damage is a major concern in clinic and public health. It is the most limiting factor in radiotherapy treatment of malignant diseases. It can also cause a serious harm to populations exposed to accidental radiation exposure or nuclear warfare. With regard to the clinical use of radiation, there has been a number of modalities used in the field of radiotherapy. These includes physical modalities such modified collimators or fractionation schedules in radiotherapy. In addition, there are a number of pharmacological agents such as essential fatty acids, vasoactive drugs, enzyme inhibitors, antioxidants, and growth factors for the prevention or treatment of radiation lesions in general. However, at present, there is no standard procedure for the treatment of radiation-induced normal tissue lesions. Stem cells and their role in tissue regeneration have been known to biologists, in particular to radiobiologists, for many years. It was only recently that the potential of stem cells was studied in the treatment of radiation lesions. Stem cells, immediately after their successful isolation from a variety of animal and human tissues, demonstrated their likely application in the treatment of various diseases. This paper describes the types and origin of stem cells, their characteristics, current research, and reviews their potential in the treatment and regeneration of radiation induced normal tissue lesions. Adult stem cells, among those mesenchymal stem cells (MSCs), are the most extensively studied of stem cells. This review focuses on the effects of MSCs in the treatment of radiation lesions.

Amelioration of the pathological changes induced by radiotherapy in normal tissues.

Damage to normal tissues remains the most important limiting factor in the treatment of cancer by radiotherapy. In order to deliver a radiation dose sufficient to eradicate a localised tumour, the normal tissues need to be protected. A number of pharmacological agents have been used experimentally, and some clinically, to alleviate radiation damage to normal tissues but at present there is no effective clinical treatment to protect normal tissues against radiation injury. This paper reviews the efficacy of pharmacological substances used after radiation exposure. The limited evidence available suggests that radiation insult, like many other tissue injuries, is amenable to pharmacological intervention. However, care must be taken in the administration of these substances for the management of different aspects of radiation damage because there appears to be a tissue-specific response to different pharmacological agents. Also, one must be aware of the limitations of results obtained from animal models, which do not necessarily correlate to benefits in the clinic; the conflicting results reported with some modifiers of radiation damage; and the toxicity of these substances and radiation doses used in published studies. Conflicting results may arise from differences in the pathophysiologic processes involved in the development of radiation lesions in different tissues, and in the markers used to assess the efficacy of treatment agents.

Growth from two transient apical initials in the meristem of Selaginella kraussiana.

A major transition in land plant evolution was from growth in water to growth on land. This transition necessitated major morphological innovations that were accompanied by the development of three-dimensional apical growth. In extant land plants, shoot growth occurs from groups of cells at the apex known as meristems. In different land plant lineages, meristems function in different ways to produce distinct plant morphologies, yet our understanding of the developmental basis of meristem function is limited to the most recently diverged angiosperms. To redress this balance, we have examined meristem function in the lycophyte Selaginella kraussiana. Using a clonal analysis, we show that S. kraussiana shoots are derived from the activity of two short-lived apical initials that facilitate the formation of four axes of symmetry in the shoot. Leaves are initiated from just two epidermal cells, and the mediolateral leaf axis is the first to be established. This pattern of development differs from that seen in flowering plants. These differences are discussed in the context of the development and evolution of diverse land plant forms.