June 29, 2019 | David F. Coppedge

Ethical Stem Cells Becoming Easier to Make and Use

Difficulties obtaining and using adult stem cells and IPSC’s are being overcome, and that’s good for all of us.

Want to grow hair? How about repair your heart or bones? Regenerative medicine is on the march, thanks to recent advances in stem cells. These are not the stem cells derived from human embryos, with all the ethical problems they entail. These are stem cells made out of your own skin.

Functional hair follicles grown from stem cells (Sanford Burnham Prebus Medical Discovery Institute). Male pattern baldness has a promising approach to a cure, thanks to work at SBP. First, they make stem cells from your blood. Then, they induce them into a stem-like state. Then, they implant them into a scaffold on the skin that starts a hair growing, follicle and all, in the right direction. After the hair takes root, the scaffold dissolves away like a dissolving stitch.

The approach detailed in the ISSCR presentation, which was delivered by lead researcher Antonella Pinto, Ph.D., a postdoctoral researcher in the Terskikh lab, features a 3D biodegradable scaffold made from the same material as dissolvable stitches. The scaffold controls the direction of hair growth and helps the stem cells integrate into the skin, a naturally tough barrier. The current protocol relies on mouse epithelial cells combined with human dermal papilla cells. The experiments were conducted in immunodeficient nude mice, which lack body hair.

The derivation of the epithelial part of a hair follicle from human iPSCs is currently underway in the Terskikh lab. Combined human iPSC-derived epithelial and dermal papilla cells will enable the generation of entirely human hair follicles, ready for allogenic transplantation in humans. Distinct from any other approaches to hair follicle regeneration, human iPSCs provide an unlimited supply of cells and can be derived from a simple blood draw.

If it works in mice, it will probably work with people. Baldness causes anxiety in 80 million Americans, not only men but anyone with alopecia (hair loss) from various causes. Stem cells that know just what to do seem like the best possible solution to a very common condition.

The start of a new era in stem cell therapy (Phys.org). Scientists at Koc University and Oxford have made a major improvement in the process of making stem cells. Shinya Yamanaka had earned a Nobel Prize for turning adult cells into stem cells, but that method required four ingredients and a virus to inject them. Look how far the technique has come since then. The race is on to reduce the ingredients from four to two, and perhaps to zero!

The challenge of the viruses used to transfer the Yamanaka factors to the skin cells sometimes acting rebelliously and inserting themselves to arbitrary parts of the chromosomes led Assoc. Prof. Önder to investigate the use of certain chemicals instead of viruses. After targeted trials, the team observed that two chemicals produced the desired results in turning skin cells to stem cells. This meant that two of the four Yamanaka factors were no longer necessary. And applying the method with two factors instead of four has reduced the waiting period to approximately a week. And even more importantly, the success rate increased up to as high as ten-fold.

The next phase of the research will involve eliminating the other two Yamanaka factors as well. In this way, it will be much easier to apply the method in clinical settings; as viruses will no longer be needed, there will be no danger of manipulating with the wrong gene or involuntarily suppressing the effects of a particular gene.

Negligible-Cost and Weekend-Free Chemically Defined Human iPSC Culture (bioRxiv). This announcement from the biological preprint site bioRxiv is good news: stem cell lab techs can have their weekends free again! Kuo et al. have developed a cheap and quick way to generate scads of iPSCs (induced pluripotent stem cells).

Human induced pluripotent stem cell (hiPSC) culture has become routine, yet pluripotent cell media costs, frequent media changes, and reproducibility of differentiation have remained restrictive, limiting the potential for large-scale projects. Here, we describe the formulation of a novel hiPSC culture medium (B8) as a result of the exhaustive optimization of medium constituents and concentrations, establishing the necessity and relative contributions of each component to the pluripotent state and cell proliferation. B8 eliminates 97% of the costs of commercial media, made possible primarily by the in-lab generation of three E. coli-expressed, codon-optimized recombinant proteins: an engineered form of fibroblast growth factor 2 (FGF2) with improved thermostability (FGF2-G3); transforming growth factor β3 (TGFβ3) – a more potent TGFβ able to be expressed in E. coli; and a derivative of neuregulin 1 (NRG1) containing the EGF-like domain. The B8 formula is specifically optimized for fast growth and robustness at low seeding densities. We demonstrated the derivation of 29 hiPSC lines in B8 as well as maintenance of pluripotency long-term, while conserving karyotype stability. This formula also allows a weekend-free feeding schedule without sacrificing growth rate or capacity for differentiation. Thus, this simple, cost-effective, and open source B8 media, will enable large hiPSC disease modeling projects such as those being performed in pharmacogenomics and large-scale cell production required for regenerative medicine.

We can expect further advances with these breakthroughs. Maybe iPSCs will some day be made on demand in short order, right in the hospital or clinic.

Great days ahead, if the progress continues. God has put into our own cells the complete instructions for making the whole body. Now we are learning ways to turn back the clock on cells that have differentiated, so that their genomes can be steered into making any kind of cell. That’s exciting, and moreover, the techniques are ethical – as long as no rogue scientist tries to turn them into sperm or eggs for a cloning experiment. Read Wesley J. Smith’s articles at Evolution News to keep up on bioethics issues.

 

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