Repair of Damage to the Brain; Part II

Comment

The Foundation's Fact Sheet of July 1998 discussed the possibility that damaged brain cells might be able to be replaced resulting in restoration of lost brain function (a "cure"?). Since then, there continues to be important scientific advances in this field, as well as a public policy discussion about ethical issues related to the original source of the embryonic brain cells that are being used.

As background, the following is a summary of the biology of brain cell development:

From the Fertilized Egg to the Functional Brain Cell

(1) fertilized egg cell reproduce embryonic pleuro-potential cells

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(2) embryonic pleuro-potential cells differentiate ectodermal stem cells

--------------> mesodermal stem cells

endodermal stem cells

(3) ectodermal stem cells differentiate skin stem cells

---------------> neuro stem cells

(4) neuro stem cells differentiate immature nerve cells

---------------> immature glia* cells

(5) immature nerve cells environmental mature nerve cells

immature glia cells factors mature glia cells

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*glia are cells that surround nerve cells and are essential for their growth and survival and for providing the insulation (myelination) of nerve fibers.

Embryonic pleuro-potential cells (Step 1) have usually been obtained from embryos discarded by fertility clinics or from embryos or fetuses following an abortion. It is these sources of cells that have precipitated public policy discussion. More about this below.

Methods are now available (and improved methods are being explored) to grow embryonic cells in tissue culture and have them reproduce and differentiate. Thus, an "eternal" source of embryonic cells is becoming available from tissue culture banks. By placing embryonic cells in a special cell culture (Step 2), the embryonic cells are stimulated to become specialized kinds of stem cells. Likewise, when ectodermal stem cells are placed in a special culture, the ectodermal stem cells become immature nerve and glia cells (Steps 3 & 4). Thus, techniques are now available to obtain a supply of immature brain cells--the cells needed for implants.

Immature brain cells are then implanted into an animal brain. The surrounding cells in the brain appear to influence the implanted cells to mature and become identical to them --- thus, a brain cell graft is now in place.

Does the graft survive? All available evidence indicated that it does! Does it become a tumor by continuing to reproduce? All available evidence indicates that it does not! Does it become functional (restore lost function)? Preliminary evidence indicates that it may! But the available evidence is based on animal not human data.

Most experiments have been done in animal models of brain damage. A few implants have been done under experimental conditions in humans following a stroke. The results in humans have not yet been reported. However, we are not aware of studies that have been done in very young animals under experimental conditions resembling cerebral palsy; but we are trying to influence scientists to explore stem cell implantation in young animals whose brains closely resemble those of cerebral palsied children. Theoretically, the developing brain should be the best environment for functional improvement to occur.

The above is the present state of the field. Now, about public policy issues. A major issue is the source of the original embryonic cells. Because they were obtained from discarded embryonic cells or aborted fetuses, should their products (the cells growing in culture) now be permitted to be used in stem cell research utilizing government funds? Some say no; others say that the material which is now available from tissue cultures should be used irrespective of their original source. The U.S. Department of Health and Human Services, the Department responsible for the National Institute of Health (NIH), has recently taken the position that it is legal for government funds to be rewarded for research using the cellular materials obtained from tissue culture irrespective of this original source. Thus, the NIH is planning to make research grant funds available in the near future to scientists working in this research field. This will be an important resource and would further accelerate studies in this research field. Up to now, all funds for this area of research came from non-government, often commercial sources. However, a small but influential group is taking the position that NIH funding would be breaking the intent of the present federal law prohibiting the use of government funds for research that threatens the well being of an embryo or fetus. Congressional hearings are being held on whether federal funding should be permitted for research utilizing cells from tissue cultures, the original source of which were discarded embryos.

Is the possibility real for restoring function (a "cure"?) to the damaged brain that resulted in cerebral palsy? We don't know - but there is light flickering at the end of the tunnel that it may be possible. We will keep you informed. Meanwhile, we continue our Foundation's research activities to prevent developmental brain damage and to improve the quality of life of persons with disabilities due to cerebral palsy and related developmental brain damage.