Parkinson’s disease treatment using umbilical cord stem cells

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population worldwide after age 60 [1,2]. It poses a significant problem in aging societies [3,4]. The progressive loss of functions of the neurotransmitter dopamine in the central nervous system characterizes Parkinson’s disease. Typical symptoms of Parkinson’s disease are slow movement, stiffness, and resting tremor. The main pathological features are extensive neuronal loss and accumulation of leukocyte inclusions in the cytoplasm [1]. The cause of nerve cell degeneration remains unknown.

Current treatment options for Parkinson’s disease patients include Levodopa therapy, a direct Dopamine receptor activator, and a brain stimulant [5]. The effectiveness of oral medications declines after five years [6]. Medicine can provide significant symptomatic benefits in the early stages of the disease but brings side effects of long-term use, including depression and dyskinesia [7, 8]. Treatment with traditional medicine only improves symptoms, easily forms drug resistance, and cannot control the progression of the disease. These treatments cannot repair damaged Dopamine projections. Hence, it is important to consider rehabilitation methods to enhance the effectiveness of the treatment. Since Parkinson’s disease patients exhibit selective degeneration of Dopamine neurons, cell replacement therapies that can generate functional Dopamine neurons may be a promising approach.

Researchers have used cell transplantation therapy for Parkinson’s disease to address the need for improving the pathology, and they consider it a potential alternative treatment in the future [9]. Applying novel approaches and developing regulatory strategies for neuroprotection is necessary based on the mechanism of action of stem cells, including growth factor secretion and reduction of neuroinflammation.

Stem cell therapy in the treatment of Parkinson’s disease.

Ineffective traditional treatments and inadequate repair capacity in the central nervous system are concerns to treat neurological diseases. The development of stem cell therapies has provided a promising approach to overcome the failure of the endogenous repair system and replace new cells in older adult’s brain. Although there are still some obstacles to clinical applications, stem cell therapy shows its great potential to treat Parkinson’s disease.

Many studies have focused on stem cells as potential therapeutic agents in neurological diseases because of their ability to replace or restore cells. Many studies have focused on stem cell therapy in spinal cord injury, spinal muscular atrophy, cerebral ischemia, amyotrophic lateral sclerosis, and other neurodegenerative diseases [10,11]. Because neurodegenerative diseases often involve regional cell loss, cell transplantation therapies can effectively restore and replace cells in damaged tissues. To achieve the effectiveness of stem cell therapy, they often propose some criteria for stem cell transplantation as follows [12,13]. 

(1) Cells must possess the molecular, morphological, and electrophysiological properties of Dopamine neurons. 

(2) grafts can reverse the motor deficits of neurodegenerative diseases. 

(3) this therapy will enable the long-term survival of neurons in humans. 

(4) the grafted cells will reestablish a dense network for functional integration into host neural circuits.

Once researchers have evaluated and achieved such goals and criteria for stem cell transplantation, treating Parkinson’s disease with stem cell transplantation is a promising direction. Typically, mesenchymal stem cells (MSCs) receive the most attention from researchers because of their property of being able to release soluble proteins (such as chemokine, cytokines, and growth factors), lipids, and other extracellular vesicles to promote cell survival and differentiation, protect cells from oxidative stress, protect neurons from death, or even regulate inflammatory processes [14].

Although we do not fully understand the mechanism of MSC induction therapy for Parkinson’s disease, it likely involves neurogenesis and vascular remodeling, anti-apoptotic effects, and therapeutic effects. Immunomodulatory and anti-inflammatory [15]. Given its ability to migrate and implant at sites of inflammation and injury, most of the effects come from paracrine expression of neurotrophic factors and cytokines.

Human umbilical cord stem cells have many superior characteristics such as multi potency, primitiveness, low risk of immune rejection, and highly proliferative cells with significant immune regulation ability [16]. because of objective factors, scientists have not yet conducted many clinical studies on treating Parkinson’s disease with umbilical cord stem cells. But with the superior characteristics mentioned above, it comes with factors such as easy to isolate, great proliferation ability, difficult to age; secretes many biological factors, such as fibroblast growth factor, brain source neurotrophic factor; and the source of autologous graft is safe. These features make umbilical cord MSCs more convincing in treating neurodegenerative diseases of the central nervous system.

Perspectives and outlook for the future

The strong possibilities for clinical application of umbilical cord MSCs arise from their ethical accessibility and efficient expansion in the laboratory to achieve therapeutically scaled. However, the mechanism of using umbilical cord stem cell therapy in treating Parkinson’s disease still needs to be clarified and studied. The process of differentiation into Dopamine neurons remains a mystery. Clarifying the cells responsible for Dopamine neuron differentiation can enhance the potential application of umbilical cord MSCs in treating Parkinson’s disease.

Reference

1. Fu, Mu-Hui, Chia-Ling Li, Hsiu-Lien Lin, Pei-Chun Chen, Marcus J. Calkins, Yu-Fan Chang, Pei-Hsun Cheng, and Shang-Hsun Yang. “Stem cell transplantation therapy in Parkinson’s disease.” Springerplus4, no. 1 (2015): 1-8.
2. Pringsheim, Tamara, Nathalie Jette, Alexandra Frolkis, and Thomas DL Steeves. “The prevalence of Parkinson’s disease: a systematic review and meta‐analysis.” Movement disorders29, no. 13 (2014): 1583-1590.
3. De Lau, Lonneke ML, and Monique MB Breteler. “Epidemiology of Parkinson’s disease.” The Lancet Neurology5, no. 6 (2006): 525-535.
4. Ali, Samii, G. Nutt John, and R. Ransom Bruce. “Parkinson’s disease.” The Lancet363, no. 9423 (2004): 1783-1793.
5. Chen, Dandan, Wenyu Fu, Wenxin Zhuang, Cui Lv, Fengjie Li, and Xin Wang. “Therapeutic effects of intranigral transplantation of mesenchymal stem cells in rat models of Parkinson’s disease.” Journal of neuroscience research95, no. 3 (2017): 907-917.
6. Jankovic, Joseph. “Motor fluctuations and dyskinesias in Parkinson’s disease: clinical manifestations.” Movement disorders: official journal of the Movement Disorder Society20, no. S11 (2005): S11-S16.
7. Obeso, José A., C. Warren Olanow, and John G. Nutt. “Levodopa motor complications in Parkinson’s disease.” Trends in neurosciences23 (2000): S2-S7.
8. Santini, Emanuela, Emmanuel Valjent, and Gilberto Fisone. “Parkinson’s disease: Levodopa‐induced dyskinesia and signal transduction.” The FEBS Journal275, no. 7 (2008): 1392-1399.
9. Vidaltamayo, Román, José Bargas, Luis Covarrubias, Arturo Hernández, Elvira Galarraga, Gabriel Gutiérrez-Ospina, and René Drucker-Colin. “Stem cell therapy for Parkinson’s disease: a road map for a successful future.” Stem Cells and Development19, no. 3 (2010): 311-320.
10. Nicaise, Charles, Dinko Mitrecic, Aditi Falnikar, and Angelo C. Lepore. “Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury.” World journal of stem cells7, no. 2 (2015): 380.
11. Mendonça, Liliana S., Clevio Nobrega, Hirokazu Hirai, Brian K. Kaspar, and Luís Pereira de Almeida. “Transplantation of cerebellar neural stem cells improves motor coordination and neuropathology in Machado-Joseph disease mice.” Brain138, no. 2 (2015): 320-335.
12. Lindvall, Olle, and Peter Hagell. “Clinical observations after neural transplantation in Parkinson’s disease.” Progress in brain research127 (2000): 299-320.
13. Lindvall, Olle, and Zaal Kokaia. “Stem cells for the treatment of neurological disorders.” Nature441, no. 7097 (2006): 1094-1096.
14. Chen, Ying, Jiabing Shen, Kaifu Ke, and Xiaosu Gu. “Clinical potential and current progress of mesenchymal stem cells for Parkinson’s disease: a systematic review.” Neurological Sciences41, no. 5 (2020): 1051-1061.
15. Sun, Liping, Dong Li, Kun Song, Jianlu Wei, Shu Yao, Zhao Li, Xuantao Su et al. “Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro.” Scientific reports7, no. 1 (2017): 1-13.
16. Shetty, Prathibha, Anirban M. Thakur, and Chandra Viswanathan. “Dopaminergic cells, derived from a high efficiency differentiation protocol from umbilical cord derived mesenchymal stem cells, alleviate symptoms in a Parkinson’s disease rodent model.” Cell biology international 37, no. 2 (2013): 167-180.