Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
Jose Inzunza
Karolinska Institutet, Sweden
Posters & Accepted Abstracts: J Cell Sci Ther
Human embryonic stem cells (hESCs) are important research tools in studies of the physiology of early tissue differentiation. In addition these cells are regarded as a promising approach to generate transplantable cells for the treatment of several diseases, and therefore offer an immense potential as a source of cells for regenerative medicine. However the possible ability of these cells to produce tumors in vivo presents a major impediment for this achievement. hESCs can obtain growth advantages in vitro by acquired mutations. The mechanisms that may influence chromosome modification in hESCs are not well known. We have performed a comparative in vitro and in vivo study on hESC lines produced in our laboratory to see if there are changes also during in vivo growth. In vivo differentiated cells and in vitro cultured hESCs were analyzed by using first comparative genome hybridization (CGH) and second a high-resolution Affymetrix SNP 6.0 array revealing DNA copy number variations. We were able, for the first time, to identify an aberrant X chromosome both in vitro and in vivo in one out of the 3 hESC line, we decteted an amplification of the whole X chromosome, possibly due to mosaicism of XY and XX cells. In the other hESC line, array results showed small amplifications and gains. The third hESC line was less altered, but contained also a new gain verified by fluorescent in situ hybridization in a teratoma in 21% of the cells. These results indicate that mutations occur during the in vivo differentiation process as well as in vitro. The potential of precancerous mutations in in-vivo conditions is important to consider for safety measures, and underlines the necessity to remove all pluripotent stem cells from the differentiated cell population that will be transplanted.
Email: jose.inzunza@ki.se