Human mesenchymal stem cells home specifically to radiation-injured tissues in a non-obese diabetes/severe combined immunodeficiency mouse model

Abstract

The therapeutic potential of bone marrow-derived human mesenchymal stem cells (hMSC) has recently been brought into the spotlights of many fields of research. One possible application of the approach is the repair of tissue injuries related to side effects of radiotherapy. The first challenge in cell therapy is to assess the quality of the cell and the ability to retain their differentiation potential during the expansion process. Efficient delivery to the sites of intended action is also necessary. We addressed both challenges using hMSC cultured and then infused to non-obese diabetes/severe combined immunodeficiency (NOD/SCID) mice submitted to total body irradiation. Furthermore, we tested the impact of additional abdominal irradiation superimposed to total body irradiation (TBI), as a model of local therapeutic irradiation. Our results showed that the hMSC used for transplant have been expanded without significant loss in their differentiation capacities. After transplantation into adult unconditioned mice, hMSC not only migrate in bone marrow but also into other tissues. Total body irradiation increased hMSC implantation in bone marrow and muscle and further led to engraftment in brain, heart and liver. Local irradiation in addition to TBI, increased homing of injected cells to the injured tissues and to other tissues outside the local irradiation field. Morphological recovery of irradiated tissues after MSC transplantation and/or differentiation of MSC into specific organ cell types needs to be investigated. This study suggests that using the potential of hMSC to home to various organs in response to tissue injuries might be a strategy to repair the radiation-induced damages.

Mesenchymal stem cells improve small intestinal integrity through regulation of endogenous epithelial cell homeostasis

“…At the time of infusion, hMSC were characterized by the expression of CD73 (SH3) and CD105 (SH2) and the lack of expression of CD45 using FACS analysis 36 and by their potential for osteogenic and adipogenic differentiation. 37 The specificity of hMSC effects was tested by the infusion of 5 Â 10 6 human skin fibroblasts (institute self-production) in the lateral tail vein 24 h after irradiation.…”

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

“…51 MSC homing to tumors is of concern as shown by human MSC localization to a murine xenogenic breast cancer SCID mouse model through monocyte chemotactic protein-1 (MCP-1), 52 which while being a potential therapeutic delivery system for cancer therapy, may pose long-term safety issues in AD treatment. MSCs concentrate in radiation-damaged and ischemic tissue, 53 but as yet active homing mechanisms have not been shown. This is may be an important advantage when treating some acute inflammatory AD with accompanying critical ischemia such as vasculitis or SSc.…”

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

“…They can be expanded ex-vivo to hundreds of million cells, maintaining their phenotype and characteristics, and used as therapies in different diseases [74,75,142]. Another property of these cells is their homing to the site of tissue injury, an ability that widens the choices for their route of administration [74,78,143]. In addition to their multi-lineage differentiation potential [113], these cells possess anti-inflammatory and immunomodulatory properties and paracrine effects that qualified them for regenerative medicine applications ( Figure. …”