Dr. Like Wu and Dr. Xiaojuan Wang

Parkinson's disease is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. This causes a reduction in dopamine secretion. The patient is presented with tremors, stiffening of the four limbs, slow and difficult movements and difficulty with maintaining balance while walking or standing. At present, the use of medications is used to treat the disease in a clinical setting. Levodopa can improve the patient's condition but only as a neurotransmitter replacement therapy and cannot stop or reverse the course of the disease, and requires a long period of time to take the medication, which can present its own series of complications. Surgical treatment, especially deep brain stimulation has had some success. But using deep brain stimulation for treating autonomic nerve symptoms can cause cognitive problems and does not have any obvious curative effects, and there are risks of developing intracranial hemorrhaging, epilepsy, depression and other complications. How to prevent or treat these complications presents significant challenges. Presently, doctors have no effective measures for preventing these complications from occurring.

Neither the neurotransmitter replacement therapy nor the surgical operation treatment can improve the brain's environment, or increase the number of dopaminergic neurons. On the contrary, the multi-Parkinson's nerve toxicity and electrode stimulation will cause the number of nerve cells to further decrease. Because of this, searching for one kind of treatment to increase the number of nervous system cells is vital.

The traditional viewpoint held that the nerve cells in the central nervous system are a kind of terminal cell. Trauma, poisoning, and pathological processes such as hypoxia-ischemia, induce neuronal loss and are irreversible processes. The pluripotency of embryonic stem cells and the multi-potential uses of adult stem cells with the ability to cross-differentiate have provided new insights into promising methods for treating Parkinson's disease. The transplantation of dopaminergic neurons to substitute degenerated neurons, restoring the integrity of the substantia nigra corpus dopamine system and improving its functioning, is likely to be a very promising therapeutic measure in the future. In recent years, treating Parkinson's disease by transplanting nerve stem cells has become the focus of much research. Obtaining adult nerve stem cells is difficult, though. Embryonic dopaminergic neuronal transplantation may reduce the behavioral flaws inherent in the PD animal model, but has ethical issues which must be addressed; therefore the most important focus should be on exploring the sources of nerve cells in other tissues.

1. With continued research, scientists have discovered that besides the presence of hemopoiesis stem cells in bone marrow, there are also marrow matrix stem cells. The marrow matrix stem cells are non-hematopoietic adult stem cells which come from the mesoderm differentiation, which can differentiate into all types of matrix cells. They also can differentiate into non-matrix cell, such as spongiocytes, star spongiocytes, nerve cells and so on. The ideal cells used for the nerve transplant should have:

.  The ability to propagate and amplify in vitro.

.  High levels of safety and reliability.

. The ability to differentiate into neuronal and glial cells.

. No need for long-term use of immunity inhibitors.

The unique characteristics of autologous marrow matrix stem cells are the reason that they are considered to be the ideal cells to be used for the treatment of Parkinson's disease and why the use of them has provided truly unique treatment prospects.

2. Marrow Mesenchyma Stem Cells When Used for Transplantation Have the       Following Merits:

. Abundant cell sources, convenience in collecting the material, not only from bone marrow, but from other sources such as fatty tissue or umbilical cord blood.

. Under certain culturing conditions, the number of cells may be increased by significant amounts in a short period of time.

. Susceptible to exogenous gene transfection.

. The ability to penetrate the blood-brain barrier through vein grafts.

. Autologous transplantation which avoids immunity rejection, tissue              matching issues and ethical and moral controversies. The results are that bone marrow mesenchymal stem cells have become the ideal seed cells for nerve stem cells transplantation and have widespread prospects in clinical applications.

3. The Study of How Marrow Mesenchymal Stem Cells Differentiate into Neuronal Cells:

The research indicates that under certain specific conditions, after induction, the marrow mesenchymal stem cells differentiate into the neuronal cells in vivo and in vitro, and there are a number of protein expressions of neurological signs. The mechanisms causing the marrow mesenchymal stem cells to differentiate are not completely clear, but the marrow mesenchymal stem cells have several "procedures" within the cell genome. Within different external environments, there will be different sets of genes turned on and thus differentiating into some kind of terminal cell. Others have thought that under different culture conditions or other different factors, the marrow mesenchymal stem cells may differentiate into cells which have neuronal morphology and express the neuronal cell markers. The technology into marrow mesenchymal stem cell induction in vitro is still perfecting.

Continuing research has also showed that there are various ways to transplant the marrow mesenchymal stem cells using the animal model, and that these stem cells may differentiate into nerve cells or astrocytes within the vivo micro environment. This can significantly restore motor functioning. The marrow mesenchymal stem cells are induced to differentiate into neuronal type cells in vitro and then have the ability to survive, proliferate and migrate.

4. The Status Quo of using Transplanted Marrow Mesenchymal Stem Cells to Treat Parkinson's Disease:

Lee [10] has shown that the transplantation of marrow mesenchymal stem cells into experimental rats with PD decreased motor dysfunction. The transplanted marrow mesenchymal stem cells in the corpus striatum can reduce motor dysfunction. Lee obtained the bone mesenchymal stem cells from the right femur bone of mature female SD rats, and then transplanted the stem cells into the female rats'  own corpus striaturn. Four weeks later, through the immunity histochemistry examination, he discovered cells in the ipsilateral striatum, hippocampus, neocortex and bilateral corpus callosum and about 15 to 20 percent of the cells expressed neuronal and astrocyte markers. The feasibility of the marrow mesenchymal stem cells autologous transplantation for the treatment of Parkinson's disease has changed the viewpoint that injured brain cells cannot regenerate and recover. This treatment method provides a new way to reconstruct the central nervous system and restore its functioning.  

Although the transplantation of marrow mesenchymal stem cells used to treat cerebral infarction, brain damage and other nervous system degenerative diseases have made much progress, the mechanisms behind nerve restoration are still not entirely clear. At present, we think the mechanisms behind the treatment for Parkinson's disease using marrow mesenchymal stem cells include:

1. After the marrow mesenchymal stem cells are transplanted into the brain, the formation of neuronal cells or astrocytes, which can express nerve symbolic proteins, can be produced and can survive in the impaired areas and even survive and migrate to other regions of the brain.

2. The marrow mesenchymal stem cells fuse with the damaged cells, causing cell phenotype changes, then substitution of the damaged cells can occur.

3. The marrow mesenchymal stem cells in the micro environments of the central nervous system can secrete brain-derived neurotrophic factors, alkalinity trophic factors and other trophic factors and stimulate the endogenous factors of the central nervous system. This promotes repair and reconstruction of the damaged tissue and reduces cell apoptosis.

4. The marrow mesenchymal stem cells make up the main components of newly regenerated blood vessels in the damaged areas. These cells have the ability to differentiate into blood vessel endothelial cells and extracellular mesenchymal cells, protecting the nerves.

5. The marrow mesenchymal stem cells are localized in the brain to create a suitable microenvironment. Through amplification in vitro or different factors, the marrow mesenchymal stem cells are induced to differentiate into nerve cells in order to replace the damaged cells, restore the damaged nerve functioning and repair the neurological pathways.

Bone marrow mesenchymal stem cells are transplanted using the following methods:

1) A three dimensional positioning system through the brain, the stem cells are transplanted into the corpus striatum.

2) Injected directly into the ventricles or subarachnoid cavity, the stem cells migrate to the damaged tissue through the cerebrospinal fluid.

3) Injected into a vein or artery, the stem cells migrate to the damaged tissue through the blood circulation.

5. Prospects:

The bone marrow mesenchymal stem cell transplantation treatment uses autologous, homogeneous variant or heterogeneous functional cells. After processing, the transplanted stem cells migrate to the specific damaged region of the patient's brain or spinal cord in order to treat various neurological diseases. Recent studies have shown that any damage to the brain after stem cell transplantation is minimal. Precise localization, repeatable injections, accurate calculations of the number of implanted cells, the variety of types of cells used and the development of high-purity cell lines used for transplantation are all aspects of the treatment. Bone marrow mesenchymal stem cells have common characteristics found in all stem cell types as well as other merits which neural stem cells and embryonic stem cells do not have. Therefore, the use of bone marrow mesenchymal stem cells to treat Parkinson's disease has brought promising new hope.

Overseas medicine: Gerontology fascicle July, 2008 29th volume 4 phase