Stand Up For Science

Scotland seems to be the place for stem cell research these days, with two announcements in the past week of new clinical trials to assess stem cell therapies.

The first clinical trial seeks to assess the capacity of limbal stem cells, corneal progenitor cells of limbus that lies at the edge of the cornea, to repair damage corneas in patients suffering from corneal blindness, the second most common cause of blindness after cataract. The only treatment currently available is corneal transplant, but as with all transplant tissue the availability of donated corneas is limited and many patients never get a transplant. While there have been several successful clinical trials (1) involving the transplant of limbal tissue from living donors or the patient themselves, particularly in cases where the patient lacks limbal stem cells due to damage to the limbus, this is the first clinical trial that will assess limbal stem cells taken from a deceased donor and grown in vitro. If it is successful it could make available an almost inexhaustible supply of stem cells to treat corneal damage.

Much of the information that lead to the conclusion that the corneal progenitor cells were located in the limbus obtained through detailed studies of the cell development and responses to eye damage in mice and rabbits (2). In 1990 scientists demonstrated that damaged rabbit corneas could be repaired by transplantation of limbal tissue alone (3), in contrast to earlier trials that transplanted other tissues as well, paving the way for subsequent clinical trials.

The second clinical trial ultimately seeks to evaluate whether injecting stem cells can promote the repair of areas of the brain damaged by stroke, though the current trial is chiefly intended to assess the safety of the procedure. This is a somewhat controversial technique since the neural stem-cell line used was derived by ReNeuron from stem cells obtained from an aborted human foetus. I don't see this as a problem; while abortion can fairly be described as the "least worst" solution for many crisis pregnancies there is no suggestion here that the abortion was carried out in order to obtain the stem cells. In such cases it is reasonable that if many people can benefit from an individual's tragedy, one that will happen in any case whether or not the subsequent research is undertaken, than it is morally justifiable to use foetal tissue obtained to generate stem cell lines. This trial builds on pre-clinical research by ReNeuron where rats with experimentally induced ischemic stroke given injections of neural stem-cells showed significantly improved sensory and motor function compared to untreated controls, even though treatment was delayed until several weeks after the stroke (4). The capacity of this approach to repair damage in a model of the most common form of stroke despite there being a considerable delay between injury and treatment gives good cause for optimism, as in most clinical cases treatment will not begin until some time after injury.

Scotland wasn't the only part of the UK getting in on the stem cell action; scientists at Imperial College London have developed a new treatment that stimulates bone marrow to release two types of stem cells into the bloodstream, that can potentially help repair damage to blood vessels and tissues such as cartilage and bone. A great thing about the treatment which was developed using rats is that it uses a well studied growth factor VEGF and a drug called Mozobil that won FDA approval for the treatment of non-Hodgkin’s lymphoma and multiple myeloma last year, so it should be easier to get approval for clinical trials than is often the case. Before that happens however the ICL team will be study the therapy in a mouse model of heart attack to determine if it does in fact help damaged tissue to heal.

These three studies demonstrate just how diverse the field of stem cell therapy has become in recent years, and how animal research underpins it all.

Regards

Paul Browne

1) Cauchi P.A. et al "A Systematic Literature Review of Surgical Interventions for Limbal Stem Cell Deficiency in Humans" American Journal of Ophthalmology, Volume 146(2), pages 251-259 (2008) doi:10.1016/j.ajo.2008.03.018

2) Dua S.D. and Azuara-Blanco A. "Limbal Stem Cells of the Corneal Epithelium" Survey of Ophthalmology, Volume 44 (5), pages 415-425 (2000) PubMed: 10734241

3) Tsai R.J. et al. "Comparison of limbal and conjunctival autograft transplantation in corneal surface reconstruction in rabbits." Ophthalmology, Volume 97(4), pages 446-455 (1990) PubMed: 1691476

4) Pollock K. et al. "A conditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke" Exp Neurol., Volume 199(1), pages 143-155 (2006) doi:10.1016/j.expneurol.2005.12.011