Frankenstein’s Stem Cells
Embryonic stem cells are simply incredible. Their pluripotency allows them to split infinitely and differentiate into every type of human cell. However, research into them has long been limited by the myriad of ethical concerns around their procurement and usage. Thanks to a research team at the American Society of Gene & Cell Therapy, this barrier may soon be broken. Using chemical treatment, the team effectively transformed some cells from a developed fetus to embryonic stem cell mimics with verified pluripotency. Soon, everyday blood donations might produce the cells used in life-saving heart disease therapy.
In 2016, Kate E. Hawkins, Dafni Moschidou, Danilo Faccenda et al. conducted this groundbreaking study at the ASGCT, a nonprofit organization dedicated to understanding and studying gene and stem cell therapies. According to their website, one of their main goals is to “use genetic and cellular therapies to control and cure human disease.” Nearly every disease could be theoretically treated by stem cells, though leukemia and myelofibrosis are the only FDA-approved treatments as of now. The study was not funded by any private organization, but rather funded through government and university grants.
Chronic conditions such as heart disease and cancer cause damage to the body’s systems over time that it cannot repair on its own. That’s where stem cells come in. Normally irreparable damage becomes feasible to fix by having pluripotent stem cells enter the affected systems, and differentiate to cell types necessary, producing a healthy, functioning organ. Artificial embryonic stem cells avoid the ethical ramifications of harvesting embryos by transforming the adult stem cells from bone marrow and blood donations to pluripotent ones. Another possibility is lossless organ donation. In a study conducted earlier this year, researchers at Michigan State University were able to create a miniature, functioning human heart within a petri dish with the use of some embryonic stem cells (Israeli et. al, 2020.) This creates a possibility of organ donation without any loss. If a sustainable artificial stem cell supply is produced, then the tens of thousands of patients on organ donation waitlists may no longer have to wait.
This study responds to the progression of inducing pluripotency in cells by investigating the possibility of solely using chemicals to do so. Previous research proved the possibility of gene editing to force the expression of pluripotent sequences, but this left a genomic footprint as well as being largely inefficient. This team of authors identified the cells shed by the fetus suspended in amniotic fluid as strong candidates for chemical induction in a previous study of theirs. All of these factors led to a (largely successful) attempt at using chemical methods to create a pluripotent cell.
The cells were obtained from late-pregnancy amniotic (womb) fluid from 3 pregnant subjects, then placed in culture dishes and provided nutrients and antibiotics for a few days. Afterwards, they were exposed to VPA (valproic acid) for a period of five days, then transported and observed in a nutrient formula over 50 days. To determine independent growth, 12 well-plates were filled with the post-VPA treatment cells, suspended in an agar solution, and later photographed. The team subsequently prepared a transduction (foreign virus insertion) of strands of lentivirus, which activate reporter genes to indicate cell differentiation. Afterwards, PCR (a DNA/RNA analysis method) was utilized on the whole culture to obtain total RNA of the culture, then individually separated single cells were analyzed using PCR. In order to investigate the metabolism of these pluripotent-induced cells, carbon dioxide production was closely monitored in highly dense well-plates. Finally, the team used a green fluorescent indicator to highlight ATP (energy) molecules and took pictures every second for half an hour to observe how it depleted.
Using a variety of methods, the scientists discovered that their treated cells demonstrated all traditional hallmarks of pluripotency (Hawkins et. al 2016.) By analyzing the produced stem cells, they found a number of remarkable discoveries. First, they found the specific DNA markers that cause pluripotency. Secondly, they found the distinct metabolic patterns of pluripotent cells. These two discoveries allow for much faster checking of pluripotency rather than running through the rigorous battery of tests every time. Lastly, they found that the VPA-treated cells are genetically and molecularly distinct from embryonic cells, while having all of the same properties and functions. If your organs are treated with these artificially produced cells in the future, scientists will be able to tell – you’ll have Frankenstein’s artificial components within you.
This research is a game-changer for the stem cell field. Identifying the cellular markers for pluripotency will accelerate research by skipping the pluripotency-tests of other studies. Not only that, but chemically transforming cells represents an imminent wave of research and treatments. However, this experiment proved the possibility with cells from a fetus, which recently lost their pluripotency and are thus easier to transform. Pluripotent stem cells obtainable en masse represent a dearth of effective treatments to previously incurable diseases and life-threatening injuries, and with it a revolution in medicine unlike any seen before. This also gives newfound hope to many chronic disease patients and their loved ones as a previously terminal condition becomes entirely temporary.
From an ethical perspective, not only was it conducted in accordance with all ethical regulations and standards, it paves the way for future ethical stem cell treatments and research. However, the report did feel a little incomplete around the method of obtaining the stem-cells, hand-waving it by mentioning how it was in accordance with laws and regulations. For a future report, the method of specifically obtaining the stem cells rather than just obtaining the subjects and their consent would be a marked improvement.
We are witnessing a new era in medical technology. Soon, the chronic diseases that plague so many will likely be a thing of the past. Artificially produced stem cells open the door to a significantly brighter future – one with far less disease and far more possibilities.
Hawkins KE, Moschidou D, Faccenda D, Wruck W, Martin-Trujillo A, Hau K-L, Ranzoni AM, Sanchez-Freire V, Tommasini F, Eaton S, et al. Human Amniocytes Are Receptive to Chemically Induced Reprogramming to Pluripotency. Molecular Therapy. 2017;25(2):427–442. doi:10.1016/j.ymthe.2016.11.014
This is the study the article is discussing. Using valproic acid treatment, researchers were able to transform developed fetal cells into pluripotent mimics with the same properties as embryonic cells, while having a different genetic signature.
Israeli Y, Gabalski M, Ball K, Wasserman A, Zou J, Ni G, Zhou C, Aguirre A. Generation of Heart Organoids Modeling Early Human Cardiac Development Under Defined Conditions. Bioengineering; 2020 [accessed 2020 Aug 26]. http://biorxiv.org/lookup/doi/10.1101/2020.06.25.171611. doi:10.1101/2020.06.25.171611
This study involves a team of Michigan State University researchers that managed to produce a miniature human heart in vitro by using embryonic stem cells. Their end-result was a heart organoid, which largely replicates and mimics the functions and abilities of a normal organ. The fetal human heart grew in real-time in the petri dish.
Frankenstein Photo Source: Allstar/Universal. Public domain, used under the Creative Commons license.