another step toward regenerative medicine -- clonal precursor cells

A recently online paper from Regenerative Medicine (May 2008, Vol. 3, No. 3, Pages 281-302) entitled The ACTCellerate initiative: large-scale combinatorial cloning of novel human embryonic stem cell derivatives might offer something toward both basic research and clinical medicine.

Michael D. West (BioTime, Inc, Alameda, CA) et al. used a shotgun-like, or random induction/selection, approach to isolate 140 cell clones (hEP as they named them)from human embryonic stem (ES)cells. These cells are not ES cells anymore. They are differentiated toward various different lineages but not terminally differentiated either. What are they? Not sure yet as of now because further characterization and comparison to all known cell types in our body is required. Are they useful? Yes. 1) these cells are relibable sources because ES cells are extremely sensitive to all kinds of environment factors and too difficult to control in experiment. Therefore ES cells with the same name from different labs may actually be different things. These hEP clones, once properly characterized, could certainly provide a reliable source for research. 2) From these, further study may induce them into different cell types needed in medical research/practice. Currently, people can only induce ES cells into a limited number of final differentiated cells and they are not pure at all. These certainly limited the progress of research and regenerative medicine. They didn't say this --but I think it is very interesting and practical -- following the same shotgun approach, these hEP cells could be induced to further differentiate down the road to become more specified cell types (randomly). Certainly, some of them should be actual tissue cells and could be useful. These might actually bypass the difficult targeted induction approach.

Ethical problems? Of course. For example, what exactly are those hEP cells or the further differentiated cells as I proposed? New entity?? Questions like these certainly exist but the research should move on because humans will benefit eventually. A quote from a pioneer Sir John. Gurdon, "if something works well, ethical concerns will disappear."

Epigenetics and cell identity

Two areas of investigation are currently of great interest to biologists. The first being what determines the identity of a particular cell, and the second being the ability of various cells to maintain their identities during cell division. Since theoretically every cell in a given organism contains the same genetic information (i.e. DNA or genome sequence), the answers do not lie within the DNA sequence itself, but rather reflect the organization of chromatin into active and inactive components, i.e. epigenetics. So, the questions become: How is the genetic information organized so that it is interpreted correctly to give a cell a particular identity and how is that organization inherited? These questions are important to understand the relationship between genotype and phenotype and are also very important for medical sciences. For example, epigenetic abnormality has been linked to cancer and other human diseases. But the underlying mechanisms remain a mystery. So, in the long-term, an understanding of these topics will have positive medical applications with respect to both diagnosis and treatment.

Epigenetics is an enormous and rapidly growing field. It started from DNA methylation about 20 years ago. Now this concept includes histone modifications, histone variants, imprinting, replication timing, and more. However when you look at these closely, you will notice that all these properties could very likely be controlled by one thing: DNA replication, when chromatin is assembled. At the time of DNA synthesis, Mother Nature could efficiently assemble all these important packaging components that give a cell the identity.