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Multiple human mesenchymal stem cell engraftment and specific homing to injured tissues


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Titre du congrès :2nd International Conference on Tissue Engineering Ville du congrès :Crète Date du congrès :22/05/2005

Type de document > *Congrès/colloque

Mots clés >

Unité de recherche > IRSN/DRPH/SRBE/LTCRA

Auteurs > ALLENET Bénédicte, CHAPEL Alain, FRANCOIS Sabine, FRICK Johanna, MATHIEU Noëlle, MOUISEDDINE Moubarak, SEMONT Alexandra, THIERRY Dominique

Date de publication > 27/05/2005

Résumé

Background. Some patients who undergo radiotherapy may develop side effects that can be life threatening. Tissue complications can result in functional alterations of organs caused by radiation-induced stem cell depletion. Stem cell therapy is a promising approach to improve radiotherapy-enhanced tissue complications. The multipotential of Mesenchymal Stem Cells (MSC), their easy isolation and high ex vivo expansive capacity make these cells good candidates for replenishment of the depleted stem cell compartment during radiotherapy. In this study, we make the assumption that radiation-induced normal tissue injuries might play a role in the recruitment of MSC for tissue repair. Methods. We isolated MSC from the human bone marrow (hMSC) and transplanted them via the systemic route into immunotolerent NOD/SCID mice. Using two models of radiation-induced lesion (total body irradiation: TBI, total abdominal irradiation: TAI), we have studied the link between tissue damage and hMSC implantation. Tissue alterations were studied by histological analysis. hMSC in tissues of transplant was quantified by real-time PCR assay 14 days after their injection. Results. In unirradiated NOD/SCID mice, hMSC homed significantly in lung (0.06% of total lung cells), muscle (0.07%) and bone marrow (0.14%). Following TBI of NOD/SCID mice at a sublethal dose (3.2 Gy), we observed an increase of engraftment in brain (0.07%), heart (0.05%), liver (0.11%), muscle (0.12%) and bone marrow (0.37%) compared to unirradiated mice. TAI (8 Gy) induced a significant increase of hMSC engraftment levels in kidney (0.10%), stomach (0.12%), liver (0.44%), spleen (0.94%), and small intestine (0.17%) compared to TBI mice. On the other hand, TAI induced liver, spleen and small intestine histological alterations. Conclusion. We conclude that mainly MSC implantation takes place in radiation-injured organs of exposed areas. Nevertheless some MSC can be engrafted in multiple organs of unexposed areas that might be related to the expected inflammation in whole body. Prospects. Preliminary results seem to show that MSC reduce radiation-induced intestinal lesion. The characterization of the capacity of MSC in intestinal functional recover is under progress in our laboratory.