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Treating Parkinson’s Disease using the umbilical cord blood mesenchymal stem cells transplantation Method

Author Admin Views Posted at 2011/11/04

Treating Parkinson’s Disease Using the Umbilical Cord Blood Mesenchymal Stem Cells Transplantation Method 

Xiaojuan Wang, Like Wu, Saichun Chu, Baolei Xu and Bo Cheng
 
Foreign Medical Science (Geriatrics) 2008 Vol.29 No.4 P.181-184
 
Abstract:
OBJECTIVE: To observe the curative effects of the umbilical cord blood mesenchymal stem cells (MSCs) implantation for the treatment of Parkinson’s disease.
 
METHODS: There were a total of 30 Parkinson’s patients at Beijing Wu Stem Cells Medical Center, from January to December 2008, who were selected, including 19 males and 11 females, aged 45-66 years old with the mean age being 58 years old, Ⅱ-Ⅳ grade according to the Hoehn-Yahr classification. The informed consent was obtained from each patient, and the treatment was approved by the Medical Ethics Committee. The routine examination showed all of the patients had normal levels of blood, urine, normal stool test, and normal liver/renal function, as well as tumor markers during the first week. During the second week, all the patients received a MSCs implantation through a lumbar puncture into the subarachnoid space. The puncture point was between the L3-L4 intervertenral space. A total of 5 mL (5 million cells) MSCs were slowly injected within 10 minutes, once per week, for four successive weeks. The Unified Parkinson’s Disease Rating Scale (UPDRS) was used to evaluate these Parkinson’s patients’ neural function. The higher the score, the more severe the damage was.
 
RESULTS: All the patients were included in the final analysis, without any loss. Compared to before the transplantation, the UPDRS showed a significant decrease 3 months after the treatment (P < 0.01). The clinical symptoms including tremors, rigidity, slow movement, and unstable posture showed obvious improvement. In addition, there was no occurrence of graft versus host disease.
 
CONCLUSION: MSCs implantation can ameliorate the clinical symptoms, as well as improve the quality of life of patients suffering from Parkinson’s disease, to a certain extent.
 
Introduction
 
Parkinson’s disease (PD) is a common neurodengerative disease that effects the elderly. The main symptoms include tremors, rigidity, slow movement and unstable posture. Both the traditional medications and surgery can not reverse the degeneration of the neural system. In addition, the dopa has neurotoxicity with the electrode stimulation and can lead to further damage and reduction of the neurons, it is because of this, that it is necessary to seek a new treatment method in order to improve the neuronal cells ammount aimes at cause of the disease, which is necessary for the treatment of PD.
According to the general concensus, the neurons of the central nervous system are a kind of terminal cell, once they are damaged due to injury, toxicosis, ischemia or hypoxia, the loss of the neurons can not be reversed.
The multipotency of adult stem cells provide a new method for the treatment of PD[1].
In this experienment, we implanted umbilical cord blood mesenchymal stem cells (MSCs) to treat PD patients and observed the effects of the stem cell implantation for PD symptoms.
1. Case Introduction
1.1) 30 PD patients were chosen on 2008-01/12 and treated at Beijing Hezhonghuaxin Medical Center, all of them were diagnosed according to the standard of instructions of PD diagnostic and management of the Royal College of General Practitioners. 19 cases were male and 11 cases were female, the age was between 45-66, and the average age was 58 years old, and their PD symptoms were divided as Ⅱ~Ⅳ level according to the Hoehn-Yahr scale. The patients were fully aware of the treatment and all the risks involved and signed a consent form before the start of the stem cell treatment according to the No. 33 regulation (regulations on administration of the hospital) issued by the State Council (China) in 2005, the treatment plan was permitted by the hospital’s Medical Ethics Committee before the study began. 
Indication of the stem cell treatment: primary Parkinson’s disease, with the Ⅱ~Ⅳ grade by the Hoehn-Yahr standard, excluding other neurodegenerative diseases and severe systemic diseases.
Relative contraindication of the stem cell treatment: ① hyperirritability or having a medical history of severe allergies ② unstable vital signs ③ malignant tumor ④ general or local serious infection ⑤ severe disturbance of an organ’s functioning such as the heart, lungs, liver or kidneys ⑥ coagulation defects such as hemophilia ⑦ a patient with a positive serological testing result such as HIV, syphilis, hepatitis B, etc.
1.2) Methods
Clinical examination: all the patients must be hospitalized and have regular physical checkups during the first week. In all of the 30 cases, the blood, urine and stool tests showed normal levels, the renal function and liver function were within normal levels, the tumor marker and chest X- rays were all normal, blood sugar level of 3 of the patients were higher than normal, and after the regular diet and oral medication treatment, the blood surgar levels were controlled and within the ideal range. The blood-lipid levels of 5 of the patients were higher than normal, including the cholesterol or triacylglycerol levels. We gave these patients medication to decrease the blood lipid levels to the normal range.
Umbilical cord blood mesenchymal stem cells (MSCs) isolated and cultured in vitro: the umbilical cord blood mesenchymal stem cells (MSCs) are all from Beijing SinoCells Biotechnology Development Co., Ltd. The cells were collected from cord blood, after the isolation and expansion, the cells were induced to differentiate into neural stem cells, after 4-6 transfer cultures, the amount of the stem cells was 1×109 L-1, , among them, 80% were CD34+ cells and 20% were neural precursor cells.
MSCs implantation[4]: During the second week, we gave the patient an MSCs implantation through an intrathecal injection, once per week, for a total of 4 times, comprising the one course of the treatment period. During the course of the treatment, the patient was placed in the left lateral position, bent at the hips, knees and neck, the puncture point was located at the L3-L4 intervertebral space, which was sterilized and the surrounding area covered with surgical olrape. The patient was then given local anesthesia with 2% Lidocaine, then we used a No. 9 puncture needle, and injected the MSCs into the subarachnoid space vertically. The patient was initially given 2mg of Hexadecadrol slowly, and then injected with 5ml of MSCs (5 million stem cells) into the subarachnoid space within 10 minutes. We then observed the patient’s initial response. There was no signs of discomfort, so we removed the needle, sterilized the puncture area, covered it wih sterilized dressing, and let the patient lay down without a pillow for 6 hours. 
Assistant therapy: We give each patient regular treatment to expand the blood vessels, anti-free radicals, treatment to nourish the neurons and treatment to stablize the cytomembrane, etc.
 
Evaluation standards: We evaluate the patient’s neural function and any symptom changes before the stem cell implantation and 3 months after the implantation, use the PD evaluation form and evaluate the patient’s condtion with a 4 part system: part 1, mental status, behaviour and mood fluctuation; part 2, daily activity; part 3, motor functioning; part 4, the complications. The higher the score a patient has, the more severe the neuronal loss is. 
 
Statistical analysis: the second author adopts the SPSS 11.5 system to deal with the data from the experient, use x(_)±s to show the quantitative data, use pairs of the test analysis for the line number, P < 0.05 to indicate the significative statistical differences.
 
1.3) Case Analysis
All of the 30 cases of the stem cell implantation treatment were completed sucessfully, no one withdrew during the treatment procedure. We do the results analysis according to the intentionality.
Patient’s independent functional score: adopt the UPDRS scale to evaluate the patient’s neural function, before the treatment, the average score is 89, and 3 months after the stem cell implantation, the average score is 56, there are statistically significant differences between them (P < 0.01), Tab 1.
 
Vital signs: during the stem cell implantation period and 3 months post implantation, the patients’ vital signs were stable.
 
Complications and side effects: 3 patients developed low fevers after the implantation, their tempretures were lower than 38 ℃, with headaches or back pain, etc. after the symptomatic treatment, they were relieved completely. No one had graft versus host response (GVH).
 
2. Case Discussion
Parkinson’s disease (PD) is a kind of extrapyramidal disease resulting from the dopaminergic neuron degeneration of the nigrostriatal system, which leads to the reduction of dopamine, the main symptoms are static tremors, rigidity, slow movement and unstable body posture. Currently the main treatment methods are medications and surgery[5]. Neither the replacement of the neurotransmitter dopamine or through surgery, can there be an improvement to the brain environment or increase the amount of dopaminergic neurons, in fact, the neurotoxicity and the electrode stimulation can lead to further damage and reduction of neurons, so it is imperative to seek a new treatment method, improve the neurons cells ammount aimes at cause of the disease, which is necessary for the treatment of PD[6-7].
The general consensus is that the neurons of the central nervous system is a kind of terminal cell, once they are damaged because of injury, toxicosis, ischemia or hypoxia, the loss of neurons can not be reversed. Adult stem cells multipotency of trans-differentiation provides a new method to treat PD[8-30]. The dopaminergic neuron implantation can replace the damaged neurons, help to improve the integrity of the Dopa system of nigrostriatal pathways and improve the functioning. This is an effective treatment method for PD[31-32]. In recent years, neural stem cells implantation for the treatment of PD has become a new point of interest in the medical community, but the main problem is that the adult neural stem cells are difficult to achieve[33-34]. The dopaminergic neurons taken from an embryo, after being implanted, can alleviate the behavioural deficits in the Parkinson’s disease animal model[35] , but there still remains some dispute over the ethics of the procedure, so further exploration of new sources of neurons is crucial.
 
The ideal source and considerations for the use of any stem cells should be[36-37]: ① do they have the ability for amplification and reproduction in vitro ② are they safe to use ③ can they differentiate into neurons and neurogliocytes after implantation ④ there is no need to use immunosuppressant for a long period. The MSCs (mesenchymal stem cells) can be adequate in such requirements.
In addition, the MSCs (mesenchymal stem cells) have some unique advantages: ① they are easier to collect, and the source is very numerous, there are enough MSCs in cord blood, bone marrow and umbilical cord, etc. ② in a proper cuture environment, they can amplify in a very short time ③ they can be transfected by exogenous genes much easier ④ they can penetrate the blood-brain barrier and can be implanted by an intravenous injection ⑤ the source of the stem cells avoid the ethical dispute. With all of these advantages, the umbilical cord blood mesenchymal stem cells (MSCs) can be ideal seed cells for the neural stem cells implantation treatment.   
 
From the experiement, all the data indicates that the umbilical cord blood mesenchymal stem cells (MSCs) implantation can improve a PD patient’s clinical symptoms such as tremors, rigidity, slow movement, unstable gait, etc., in a short period of time. The possible mechanism are: ① the MSCs, after implantation into the patient’s brain tissue, can differentiate into neuron-like cells or astrocytes which can express protein markers of neurons, and those new cells can survive in the damaged area even more within the brain global[38]. ② In the microenvironment of the central nervous system, the MSCs can produce neurotrophic factors, Basic Fibroblast Growth Factor (BFGF), or stimulate the damaged area by secreting endogenous factors to help repair the damaged area and reduce the cell apoptosis[39-40]. The MSCs are the main part of the new blood vessels in the damaged area, and they can differentiate into vascular endothelial cells and extracellular matrix, help to protect the neurons, and help the vasculogenesis[41]. They can also create a proper local microenvironment, cause the MSCs to have full differentiation into neurons proliferated in vitro or induce the differentiation method, replace the damaged neurons and rebuild the neural functional area and neural Pathways [42] 

If the MSCs can keep the long term treatment effects, then the advantages are obvious compared to other traditional treatment methods for PD. We still need further research to fully understand the true potential of this treatment method.

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