The stem cell dream has been present for years, but so far the dream has outpaced reality. Only A handful of stem therapies are actually useful treatments at present.

A Japanese researcher has succeeded in making iSC into eggs, and discovered that you needed supporting ovarian tissues to make the system work in mice.

Some stem cell treatments deemed  successful may have actually been due to dead cells or immunity-stimulating debris causing increased functionality, particularly in the heart.

Interestingly, as stem cells slowly differentiate into heart cells, there is a stage of cardio myocyte that beats on its own. This leads to arrhythmias if there is insufficient differentiation in stem cell treatment. Only later in differentiation does the myocyte stop beating on its own and rely upon a signal to contract, as the adult heart does.

A 3-D model of pluripotent heart stem cells has been seen to self organize. Mostly researchers have focused on building tissue around a scaffold to re-create the heart chambers structure, but a heart organoid, known as a cardioid, has been created by adding six signaling factors.

Stem cells in culture mutate about 840 times faster, creating problems. I have a friend who has his own iSC dopaminergic stem cells injected into his brain,  but the tissue culture media worryingly shows a teratoma, a type of tumor with all three embryonic tissue lines.

Stem cells had previously been classified as naïve or prime. An intermediate stage is now been discovered called  the rosette stage. The developing organism must be sure before it goes ahead.

Whether to make pluripotent stem cells from a persons own tissue, and use it for replacement therapy in that single individual, or to take a cell line that has been vetted, and use it in everybody, accepting the necessity of immunosuppression, is currently being worked out. The Japanese groups are generally going with this latter “allogenic” package and working to match histocompatibility sites.

Parkinson’s treatment is unlikely to be a cure, since the transplanted cells may eventually become diseased themselves. Stem cell treatment can improve symptoms potentially, but can’t alter the course of the disease.

Using fetal cells has proven very problematic, since a given procedure for Parkinson’s may require 4 to 12 fetuses per patient, and you have ethical problems besides.

Spinal cord injury is plagued by inter-species architectural differences, and knowing exactly how severe the injury actually is. Researchers also have to be sure they are not going to make the situation worse.

Chimeras are developing as a research bonanza. The idea is to take a lower species, block the development of a given organ, then inject a higher species stem cells which are more likely to fill the niche if they don’t have domestic competition. Many efforts are directed towards developing human organs in subhuman species. When using primates as the sub species, however, an additional step, blocking the possibility of stem cells becoming neurons is advisable. There’s a lot of ethics in this area.

The pancreas is the area of greatest work at the present time. Keeping an embryo alive in a dish is very important, but difficult. The “14-day rule” is being extended.

The suffix “oid” is getting very popular. We have organoids, spheroids, blastoids, and assembloids. I was a bit surprised to hear how self organizing these tissues are, and also how important are the accessory, helper cells: the ovarian support tissues, the astrocytes in the brain, the pigmented epithelial layer of the eye, the pericytes in blood vessels.

Jeanne Loring is trying to save the white rhinoceros. Just cloning the rhinoceros is not good enough. Some mutations in the germ-lines are needed to make different individuals. This also requires going from Induced stem cell retrograde over to sperm cells; the only two white rhinos still alive or both females.

Currently it requires great technique to take a somatic cell back to induced stem cell. These talented people are called “cell whisperers”.
Mention is made of the Chinese hamster ovaries cells that are commonly used to produce therapeutic proteins. They tend to float in the reactor as single cells. Pluripotent  stem cells are more fragile, and need to grow in aggregates. You must form sheets of the stem cells in order to get them to take  in the eye, for instance, in order to get them to form retinal pigmented  epithelial cells, photo receptors, horizontal cells, bipolar cells, amacrine cells, and ganglion cells. “We transplant 10-20,000 cells per eye. To recover vision you probably need hundreds of thousands of cells. Most people appreciate even a slight improvement in vision, however”.

“ All models are wrong, some are useful“ is the guiding principle of leading edge stem cell Whisperers.

—Dr. C.

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