Therapeutic cell types obtained from iPS cells demonstrate abnormal expansion and early cellular aging

Feb 12 2010

Advanced Cell Technology, Inc. or “ACT” (OTCBB:ACTC) reported that a range of therapeutic cell types obtained from induced pluripotent stem (iPS) cells exhibit abnormal expansion and early cellular aging. The research, which appears online (published-ahead-of- print) in the journal STEM CELLS by ACT and its collaborators at Stem International (SCRMI), Harvard Medical School, and the University of Illinois, compares a variety of replacement cell types derived from human iPS cells with their embryonic stem (ES) cell counterparts. The findings support the use of ACT’s single blastomere-derived human embryonic stem cell lines which do not display early aging.

“Before clinical application, it will be necessary to determine the cause and extent of such abnormalities, and whether they also occur in stem cells generated using different reprogramming methods”

The research shows that human iPS cells can generate blood, vascular and retinal cells with characteristics similar to those derived from ES cells, but with a dramatic decreased efficiency. However, in distinct contrast to the ES cell derivatives, major differences were observed in cells derived from iPS cells, including significantly increased cell death (apoptosis), severely limited growth and expansion capability, as well as a substantially decreased capacity to generate blood progenitors. After further differentiation into red blood cells, over a thousand-fold difference in expansion capability was observed in iPS cells versus ES cell progenitors. Although vascular cells derived from iPS cells were capable of forming capillary-like structures, the cells also demonstrated early cell aging (senescence). Similarly, retinal cells derived from iPS cells also displayed early signs of aging.

“Before clinical application, it will be necessary to determine the cause and extent of such abnormalities, and whether they also occur in stem cells generated using different reprogramming methods” said Robert Lanza, M.D., Chief Scientific Officer at ACT, and senior author of the study. “Fortunately, we think the problem may be related to the use of viruses. Preliminary results suggest that these abnormalities are significantly reduced using stem cells generated using proteins (without the use of viruses or genetic manipulation). Although there is excitement that iPS cells can serve as an embryo-free source of stem cells, it would premature to abandon research using embryonic stem cells until we fully understand what’s causing these problems.”

Rapid progress is being made towards controlled differentiation of human iPS cells into specific tissue types, such as heart, liver, and eye including retinal pigment epithelium (RPE). Although these studies clearly suggest a similar differentiation potential between iPS and embryonic stem cells, it is unclear whether they can be expanded into homogeneous cell populations suitable for use in drug discovery and clinical translation.

“A major hallmark of ES-derived cells is the high recovery and proliferative capability of the cells,” stated Shi-Jiang Lu, Ph.D., Senior Director of Stem International and co-senior author of the paper. “We compared the characteristics of cells derived from iPS and ES cells, and found that blood and vascular derivatives from iPS cells display abnormal molecular and/or cellular processes compared to their corresponding ESC counterparts. Similarly, RPE cells derived from iPS cells began senescing in the first passage, indicating the observed phenomenon is not limited to hemangioblastic lineages.”

“This study further supports our single blastomere-derived human embryonic stem cell technology platform, “stated William M. Caldwell, CEO and Chairman of ACTC. “More research is clearly needed before we can advance iPS cell technology into the clinic. However, until this technology is perfected, we believe embryonic stem cells will play an important role in helping patients suffering from a range of debilitating diseases.”