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November 06-07, 2019 | Tokyo, Japan
Volume 02
Journal of Clinical Genetics and Genomics
STEM CELLS AND REGENERATIVE MEDICINE
PEDIATRICS AND CHILD CARE
International Conference on
2
nd
World Congress on
&
J Clin Gen Genomics, Volume 02
Stem Cells 2019 & Pediatrics Congress 2019
November 06-07, 2019
Genetic changes at chromosomal and DNA level during long term cultivation of hES
cells
H
uman 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; 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.
Biography
Jose Inzunza is an associate professor and senior researcher at the Department of Biosciences and Nutrition, Karolinska Institutet (KI). He
received his doctorate in obstetrics and gynecology at Karolinska University Hospital, KI. With a specialization in cytogenetics, he worked on
his doctoral work with a project in clinical application of preimplantation genetic diagnosis (PGD). He has also been involved in the develop-
ment and implementation of the laboratory for derivation and differentiation of human embryonic stem cell research at KI. This was the first
bank of human embryo stem cells in Sweden and Scandinavia. Jose has also worked with cellular re-programming. Today, Jose's line of
research is in stem cells and tumorogenesis and genetic stability of these cells during the differentiation process.
jose.inzunza@ki.seJose Inzunza
Karolinska Institutet, Sweden