TY - JOUR
T1 - Teratoma Formation by Human Embryonic Stem Cells is site-dependent and enhanced by the presence of Matrigel
AU - Prokhorova, Tatyana A
AU - Harkness, Linda M
AU - Frandsen, Ulrik
AU - Ditzel, Nicholas
AU - Burns, Jorge S
AU - Schroeder, Henrik Daa
AU - Kassem, Moustapha
PY - 2008/4/7
Y1 - 2008/4/7
N2 - When implanted into immunodeficient mice, human embryonic stem cells (hESC) give rise to teratoma, tumour-like formations containing tissues belonging to all three germ layers. The ability to form teratoma is a sine qua non characteristic of pluripotent stem cells. However, limited data is available regarding the effects of implantation site and the methods employed for implantation on the success rate of teratoma formation. In the present study, the rate of teratoma formation in immunodeficient mice was site-dependent: sub-cutaneous (25-100%), intratesticular (60%), intra-muscular (12.5%) and under the kidney capsule (100%). Co-injecting the hESC with Matrigel increased subcutaneous teratoma formation efficiency from 25% to 100%. We did not observe site-specific differences in the teratoma composition. However, subcutaneous teratomas were quite distinct, easy to remove and caused minimal discomfort to the mice. Also, subcutaneous teratomas displayed more complex structures and larger proportion of solid tissues as opposed to cyst formation which dominated the teratomas formed at the other sites. Interestingly, a chromosomally abnormal hESC with trisomy 20 formed teratomas where the ratio of differentiated to un-differentiated tissues was significantly decreased suggesting defective pluripotency of the cells. In conclusion, subcutaneous implantation of hESC in presence of Matrigel appears to be the most efficient, reproducible and the easiest approach for teratoma formation by hESC. Also, teratoma formation can be employed to study the development defects exhibited by the chromosomally abnormal hESC lines.
AB - When implanted into immunodeficient mice, human embryonic stem cells (hESC) give rise to teratoma, tumour-like formations containing tissues belonging to all three germ layers. The ability to form teratoma is a sine qua non characteristic of pluripotent stem cells. However, limited data is available regarding the effects of implantation site and the methods employed for implantation on the success rate of teratoma formation. In the present study, the rate of teratoma formation in immunodeficient mice was site-dependent: sub-cutaneous (25-100%), intratesticular (60%), intra-muscular (12.5%) and under the kidney capsule (100%). Co-injecting the hESC with Matrigel increased subcutaneous teratoma formation efficiency from 25% to 100%. We did not observe site-specific differences in the teratoma composition. However, subcutaneous teratomas were quite distinct, easy to remove and caused minimal discomfort to the mice. Also, subcutaneous teratomas displayed more complex structures and larger proportion of solid tissues as opposed to cyst formation which dominated the teratomas formed at the other sites. Interestingly, a chromosomally abnormal hESC with trisomy 20 formed teratomas where the ratio of differentiated to un-differentiated tissues was significantly decreased suggesting defective pluripotency of the cells. In conclusion, subcutaneous implantation of hESC in presence of Matrigel appears to be the most efficient, reproducible and the easiest approach for teratoma formation by hESC. Also, teratoma formation can be employed to study the development defects exhibited by the chromosomally abnormal hESC lines.
U2 - 10.1089/scd.2007.0266
DO - 10.1089/scd.2007.0266
M3 - Journal article
C2 - 18393673
SN - 1547-3287
JO - Stem Cells and Development
JF - Stem Cells and Development
ER -