Lines of communication: advances in stem cell policy.

• Position: Discussion

MR. STEIGER:

Now I think we're going to be introducing our speakers, Professors Davis and Grega. As a bioethicist and legal scholar, Professor Dena Davis has been the recipient of prestigious grants, fellowships and visiting scholar appointments. She has published over 50 articles in the area of law and medicine--from cloning to genetic engineering--and has lectured and taught at universities and biomedical research institutions around the globe. She is the author, most recently, of Genetic Dilemmas: Reproductive Technology, Parental Choices and Children's Futures.

Dr. Davis holds an adjunct appointment at Case Western Reserve University's Department of Biomedical Ethics, and is a faculty associate in CWRU's Center for Genetic Research Ethics and Law. She is a recent appointee to the National Institutes of Health Committee that will determine how the NIH supports stem cell research.

I have the personal pleasure of having her for a class this semester, and I will say that anybody who has the opportunity next semester, or at some point in the future, should do so.

MS. BAKER:

Good evening and thank you again for coming. I'd like to introduce our other speaker, Dr. Grega.

Dr. Grega was named CSCRM [Center for Stem Cell & Regenerative Medicine] Executive Director in 2004. She has had a distinguished career in biomedical research, biotechnology business development, program management, e-commerce and global marketing. CSCRM is a multi-institutional center composed of investigators from Northeast Ohio's major medical and biomedical research centers, including University Hospitals, the Cleveland Clinic and Athersys, Inc. The Center provides a comprehensive and coordinated bench to bedside approach to regenerative medicine, including basic and clinical research programs, biomedical and tissue engineering programs, and the development and administration of new therapies to patients.

MR. STEIGER:

Without further adieu: Dr. Debra Grega.

DR. GREGA:

Thank you very much. I want to thank the organizers for the invitation and the opportunity to meet with this group and provide some information on the issue of stem cells and our stem cell policy. I'm going to give a bit of an overview on the main technical issues of stem cell work because without that it's hard to frame the main concepts for regulatory, legal, and ethical issues for the research.

So, stem cell therapeutics has really captured the imagination of the public, in addition to the biomedical community, because we have this opportunity for really replacing damaged tissue as opposed to just essentially putting a Band-Aid on damage and disease; and, as I point out here, it can be with undifferentiated cells all the way to engineered-type cells. So, today, as I said, I'm going to give a bit of an overview on stem cells, and then the impact on the science of therapeutics.

[I'd like to give] a very brief plug in terms of organizations that we have here in Ohio. The NCRM, which is the National Center for Regenerative Medicine, (2) is made up of the Center for Stem Cell and Regenerative Medicine (3) and the Clinical Tissue Engineering Center; (4) those two are funded by the State of Ohio Third Frontier Program, (5) and have those funds really in terms of late-stage research development leading into clinical and commercial outputs. So, we've been quite fortunate in that respect.

The other member of the NCRM is the Cleveland Cord Blood Center; (6) it was recently established in 2007 and provides a public bank for cord blood collection for a nationwide network. We also participate in the Armed Forces Institute for Regenerative Medicine, (7) and that is a national consortium of institutions bringing innovative regenerative medicine technology therapies for use with returning military from the Iraq and Afghanistan conflicts. And so, I just point this out in terms of local resource.

CHARACTERIZING CELLS

So, stem cells; what are they, why do people care about them? Well, stem cells can be characterized a number of ways. They're used, and function, routinely, in animal systems to repair the body, and they vary in type depending upon whether a stem cell can replace an entire organism--that's called pluripotent--all the way down to multipotent, which is really a stem cell that can only turn into a couple kinds of tissues.

Another way to classify stem cells is based on where you're getting those cells from. Are you obtaining them from an embryonic or an adult source? Embryonic stem cells can come in different flavors, also. The classifications, generally--as I've put on the slide--the one that is most controversial I've listed first, in terms of cells that are derived from a fertilized egg; it's a 5-day old embryo. You can also obtain embryonic stem cells from an egg that is unfertilized that's been manipulated, and that's with somatic cell nuclear transfer, and I'll explain a little more about that in a few minutes.

You can also obtain embryonic stem cells from late-stage embryos and fetuses, which is done in a variety of locations around the world. Finally you can also obtain embryonic-like stem cells from reprogrammed adult cells via a technology called induced pluripotency, and I'll explain a little bit more about that in a few minutes.

Adult cells, stem cells, are cells that are obtained from any organism, any animal, after birth. The source can be the bone marrow or many other tissues. Most people have heard about bone marrow transplantation in terms of cancer treatments. Adult stem cells also include umbilical-cord-derived stem cells because the baby is already born and you're harvesting these cells from the placenta and umbilical cord.

So, what does this pluripotent terminology mean? Well, in terms of development, all the stem cell work really comes back to normal development. I won't dwell on this for very long. But the blastocyst that I have in the upper right (8) is really that 5-day-old development embryo where stem cells can be isolated from. If you let that embryo develop, it would develop along this ectoderm, mesoderm, and endoderm lines forming different tissue types: skin and nervous system for the ectoderm, that outer cell shell; the mesoderm, muscle and so on; and the GI tract from the innermost layer the endoderm. When we talk about multipotent stem cells, in general they are differentiating along these tissue lines.

EMBRYONIC CELLS

But when we talk about embryonic cells, really we're getting into the issues of cloning. Therapeutic and reproductive cloning have stirred a lot of controversy. And since everyone is interested in commercializing, I'm sure, at some point, we are going to see a Friendly Frank's Cloning offering to make you new again.

Getting back to the issues on embryonic cells. As I said, you can isolate and develop cell lines, embryonic cell lines, from a 5-day-old embryo; and that looks sort of like this cartoon. And you take the ICM, inner cell mass, and turn it into a perpetual cell line. The advantages of embryonic cells [are] that you can make these lines and you can differentiate them into a variety of things. But, at this point, we really don't have the technology to control how these cells differentiate, and that's why at this point they're really not ready for prime time in terms of clinical utility. We have to have a better handle on the technology, but we're moving in that direction.

A way of forming embryonic stem cells is cloning which I have illustrated with the diagram. For cloning purposes, I mentioned that you can do this somatic cell nuclear transfer (SCNT). For SCNT you take an egg, take the nucleus out of the egg and replace it with a nucleus from a somatic (non-gamete) cell. So, we could make a personalized cell line for everybody in this room by taking a skin cell, taking the nucleus out and popping it into an egg; and then, you can coax that into developing as if it were a fertilized egg.

If you then at the 5- to 7-day period, treat that like a fertilized egg/embryo of 5-7 days and take this inner cell mass, you can turn that into specialized cells that act like embryonic stem cells, that are genetically identical to you, and that could turn into any tissue. If you, instead of deriving the cell line at this point, take that blastocyst, and put it into a surrogate mother, you could wind up with a cloned organism; Dolly the sheep is an example of this.

And so, the difference between reproductive and therapeutic cloning is whether you turn the cells into cell lines or whether you turn them into an organism. There has been universal, worldwide rejection of reproductive cloning. The animals that have been derived this way have health and genetic issues, and so it is not considered an ethical approach in humans.

So, as I mentioned, the somatic cell nuclear transfer is swapping the old nucleus out for the patient's nucleus. Since most folks are familiar with computers these days, I provide this analogy: removing the nucleus of the egg = erasing your hard drive--so, you're essentially deleting all the programs--if you installed a new operating system, that is taking that nucleus from the skin cell and transplanting it in the egg; and then, reboot the system to derive the cell lines that are of interest.

PLURIPOTENCY

Now, I mentioned yet another way to determine and to form embryonic cells, and this is induced pluripotency. Sorry for all the...