Jacobs Journal of Bone Marrow and Stem Cell Research

Genetic Alterations Acquired During Culture Expansion of MSC Leads to Widespread Tissue Engraftment and Increased Differentiation Potential in Mice

Published on: 2017-06-09

Abstract

Mesenchymal stem cells (MSC) are currently being tested as treatment for a variety of diseases. We have little information about the changes that occur during isolation and expansion, and the ultimate disposition of MSC in the body. We have shown that MSC isolated from the bone marrow of mice and expanded in culture undergo spontaneous mutations within oncogenes yet retain tri-lineage differentiation potential. Here we define the surface marker expression of these cells and compare it to the marker expression of previously isolated and characterized cultured pluripotent cells. Culture expanded spontaneously transformed MSC (stMSC) infused into immune competent mice can be recovered from all peripheral tissue as endoderm, ectoderm and mesoderm lineages. Both direct transdifferentiation of cells to organ appropriate lineages and fusion with host cells occurs and cellular function is maintained. stMSC have a competitive advantage over native MSC and freshly isolated MSC resulting in higher levels of engraftment with stMSC. stMSC injected into blastocysts contribute to all cellular lineages including the hematopoietic system, however long term hematopoietic function is not achieved: aplastic anemia and marrow failure occur after 14 weeks. These findings suggest that culture expansion of cells has the potential to introduce genetic mutations which have long term consequences. Infused MSC may be long lived in the body, and reside in a wide variety of tissues however long term function may not persist. Use of these cells for clinical therapy must be done with caution as the long term consequences in humans is not yet known.

Keywords

Mice; Animal Models; Mesenchymal Stem Cells; Cell Culture; Pluripotency