Cell Transplantation
Summary:
Cell transplantation of differentiated dopaminergic cells directly into affected areas of the brain has shown promising results in potentially treating Parkinson Disease and other movement disorders. After three years post-transplantation, a 60% equivalent of levodopa intake can be achieved allowing pharmaceutical treatment to be greatly reduced or even stopped. Varying techniques used for transplantation range from craniotomy with open cavity to stereotactic needle insertion. Targets within the brain also vary from study to study.
Stem cells are the building blocks from which all other cells in an organism are derived. They can differentiate, evolving into specialized cells that can be introduced into the desired area of the body to take on the function and characteristics of the surrounding cells. They are also self-replenishing and can produce more stem cells. There are two primary categories: embryonic and adult. Both kinds are capable of differentiating into specialized cells, but there are more stem cells in a 3-5 day old embryo (approximately 150) then there are in adult stem cells like those found in bone marrow for example. Adult stem cells are present in tissue and organs, lying dormant and undifferentiated until needed to repair any damage. Embryonic stem cells in animal studies have been induced to differentiate into dopamine-producing cells, suitable for direct transplantation into the areas of the brain that are destroyed by Parkinson Disease. Transplants performed on rats, with symptoms similar to PD, have resulted in restoration of damaged brain cells, production of dopamine and improvement in symptoms.
Ethical debates have centered on the use of human embryonic stem cells because the extraction of the cells results in the destruction of the embryo. This, and the lack of a sufficient supply of cells (may require the use of 6 – 8 fetuses per patient), has caused researchers to seek out alternative sources. Several candidates currently being reviewed include porcine fetal cells and human retinal pigmented epithelial (hRPE) cells. Use of the porcine fetal cells comes with several drawbacks including life-long immunosuppressive drugs, low cell survival rate and potential infection. hRPE cells do not require immunosuppression, have long cell survival and are available in sufficient quantity. Self-regulation of hRPE dopaminergic properties is currently being looked at in animal studies, but should move to human trials in the near future.
Potential benefits:
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Restoration of dopaminergic neurons
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Production of dopamine and dopamine precursors without dyskinesia
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Elimination or significant reduction of medication
Risks:
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Infection
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Potential severe worsening of symptoms
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Rejection of transplanted cells
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Irreversible surgical procedure
Obstacles:
Current research:
Spheramine(TM) is a novel, implantable cell based potential therapy for PD, consisting of cultured DA- producing human retinal pigmented epithelial (hRPE) cells on gelatin microcarriers to test the safety and efficacy of intrastriatal implantation of Spheramine in Hoehn and Yahr stage III and IV Parkinson's patients using stereotaxic implantation.
The present proposal is to follow patients enrolled in this study for another five years, taking the follow-up in the treated patients out for 5 to 10 years. On the basis of uncontrolled reports of small numbers of patients, the group postulates that the patients will have progressive clinical improvement for 3 - 4 years followed by a plateau and possibly a decline 6 - 8 years after transplant.
Resources
[1] Cell Transplantation for the Treatment of Parkinson's Disease from Seminars in Neurology; Thyagarajan Subramanian, M.D.
[2] United States: Stem Cells: Their Promise, Their Problems [no longer online], article by Kingsley L. Taft
[3] Stem Cell Transplantation: past, present and future, Medico Frontiers - Diagnostics; Dr Maheboob M Basade
[4] Fetal Cells Help Parkinson’s [no longer online] (Ivanhoe First), By Julie Monheim, Ivanhoe Health Correspondent
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