False-colored scanning electron micrograph of human embryonic stem cell (gold) growing within a cradling cluster of supporting fibroblasts. Image courtesy of Annie Cavanaugh, Wellcome Images
The trouble within stem cells
Inducing human pluripotent stem cells to become any kind of desired cell has the potential to transform medicine: Doctors could, for example, repair, rebuild – maybe even build anew – damaged or diseased organs.
Of course, nature has had millions of years to master the process – and it doesn’t often even attempt things like regeneration. Humans are strictly rank beginners, still struggling to fully understand the countless complexities of biological construction and overcome the myriad obstacles to success.
Chief among them is the concern that induced stem cells might carry or create mutations that, in the process of differentiation and growth, would introduce or exacerbate disease, rather than cure it. A 2011 paper published in Nature by Kun Zhang, PhD, at UC San Diego, for example, found that genetic material of reprogrammed cells may in fact be compromised.
Nowhere is this more worrisome than in efforts to find stem cell-based therapies to treat cancer, which is essentially a disease of gene mutations. The greater the “mutational load,” the greater the chance of cancer.
In a new paper, published in the journal Cell Reports, Louise Laurant, MD, PhD, adjunct assistant professor in the Department of Reproductive Medicine at UC San Diego School of Medicine, and colleagues describe analyses of two sets of human embryonic stem cell (hESC) lines.
They showed for the first time that different genetic aberrations tend to occur at different stages of development in hESCs. During preimplantation embryo development and early derivation, mutations are mainly deletions or “loss of heterozygosity,” which occurs when some copies of primary nucleobases (cytosine, guanine, adenine, thymine and uracil) are missing.
Conversely, long-term culturing of hESCs aberrations are more frequently duplications of genetic information.
The findings reinforce the importance and need to measure and monitor the genetic integrity of hESCs, and specifically point to areas of concern.
Serious efforts are being made in this regard. For example, Steven Dowdy, PhD, professor in the UC San Diego Department of Cellular & Molecular Medicine, recently published a paper describing a simple, easy RNA-based method of generating human induced pluripotent stem cells. You can read the news release here.