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    The what, who and why of stem cells in ophthalmology: Part 1

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    I recently came across an interesting news release from International Stem Cell Corporation (ISCO) announcing that it had formed a new business unit, Cytovis, to focus on stem cell programmes in ophthalmology, including CytoCor for the cornea and CytoRet for the retina.

    That got me thinking about how little I knew about what was going on in stem cell research in ophthalmology, despite having written about two developments in the field, the London Project to Cure Blindness and the University of California Irvine (UCI) programme to develop an artificial retina based on stem cell research.

    I decided to become better informed by taking a closer look at what was happening in this field, and present that story.

    For better or for worse?

    Commenting on a EuroRetina Meeting held earlier in 2008, John Morrow of Newport Biotech Consultants noted, as reported by Ophthalmology Times Europe in October 2008: "Stem cells are looked upon as either an ethical train wreck or the gateway to the alleviation of human illness, depending on which side of the political spectrum one resides. This unfortunate notoriety has resulted in unprecedented coverage in the media, but this has not done much to advance the cause of this technology. Yet recent ophthalmologic research suggests that the medical applications of stem cells hold notable promise for the treatment of ocular degenerative conditions and that realization of this potential may come about in the near future."

    I think Dr Morrow's thoughts eloquently sum up the subject. Stem cell research is politically charged but holds tremendous promise for the future, especially in ophthalmology.

    So, what are stem cells?

    Every organ and tissue in our bodies is made up of specialized cells that originally come from a pool of stem cells in the very early embryo ('embryonic stem cells'). Throughout our lives we rely to a much more limited degree on rare deposits of stem cells in certain areas of the body ('adult stem cells') to regenerate organs and tissues that are injured or lost, such as our skin, our hair, our blood and the lining of our gut.

    Stem cells are like a blank microchip that can be programmed to perform particular tasks. Under proper conditions, stem cells develop or 'differentiate' into specialized cells that carry out a specific function, such as in the skin, muscle, liver, or in the eye. Additionally, stem cells can grow extensively without differentiating and give rise to more stem cells. These two characteristics, 'pluripotency' and 'self-renewal', distinguish stem cells from other cells in the body and give stem cells their tremendous therapeutic promise for a wide range of degenerative diseases.

    The four types of stem cells

    The four most commonly used and described classes of stem cells are embryonic stem cells (embryonic SCs, or human embryonic stem cells hESCs), 'induced pluripotent stem cells' (ipSCs), 'adult stem cells' (adult SCs) and 'parthenogenetic stem cells' (hpSCs).

    Besides the embryonic and adult stem cells already used by the body, two other classes of stem cells are increasingly used in medical research, the induced pluripotent stem cells and human parthenogenetic stem cells.

    Embryonic stem cells are derived from fertilized human eggs ('oocytes') in the very early stages of development. They are truly pluripotent, in principle enabling them to become any body tissue and thus providing their tremendous clinical potential. However, embryonic stem cells are associated with significant ethical, political and religious controversy since a fertilized egg, under the right circumstances, has the potential to develop into a human. Another major (albeit much less published) issue with embryonic stem cells is that, since they essentially are a transplant from one person to another person (allogeneic treatment), therapeutic cells and tissues derived from embryonic stem cells can be expected to provoke an immune response from the recipient and be rejected.

    In contrast, induced pluripotent stem cells are adult and fully differentiated cells (e.g., skin cells) that are chemically, physically, genetically or otherwise driven back to earlier developmental stages. While creation of such cells does not involve the use or destruction of a fertilized egg, it does require dramatic changes in gene expression that may have unknown biological impact and likely will be subject to substantial scrutiny by regulatory authorities before any approval for therapeutic use. Also, due to immune rejection, induced pluripotent stem cells have to be derived from the patient themselves (autologous therapy), which significantly limits clinical use and adds time and cost that will be increasingly difficult to implement in cost-contained healthcare systems worldwide. Finally, induced pluripotent stem cells cannot be used for hereditary diseases therapy because of bearing the same genetic defects.

    Adult stem cells are rare cells found in various organs or tissues in a person that has a limited ability to differentiate into cells with specific functions. They are older and less powerful than other types. While these stem cells do not require use or destruction of a fertilized egg or extensive manipulation of gene expression, they are rare and hard to identify and they generally proliferate poorly, thus making it hard to produce therapeutic amounts.

    Parthenogenetic stem cells are derived from activated human oocytes. Parthenogenesis is a form of asexual reproduction in some amphibians and plants but does not occur naturally in mammals, including humans. ISCO scientists have discovered a process for chemical activation of human eggs, similar to what the sperm does in normal fertilization but without any involvement of a male sperm. ISCO claims that this process results in hpSCs that are as pluripotent and proliferate as embryonic stem cells, yet avoid the ethical, political and religious controversy around use or destruction of human embryos with potential for viable human life. Furthermore, since there is no forced change of gene expression patterns, hpSCs are not likely to face the same safety and regulatory hurdle as induced pluripotent stem cells. Most importantly and unique relatively to all other stem cell classes, hpSCs can be produced in a simplified immunogenetic ('homozygous') form that enables each line to be an immune match for many millions of people (ISCO's first line is an immune match for an estimated 75 million people worldwide).


    Table 1: Characteristics of the four types of stem cells
    International Stem Cell Corporation has kindly provided Table 1 that describes the characteristics of the various types of stem cells (ISCO specializes in Parthenogenetic stem cells).

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