Mesenchymal stem cells (MSCs) are multipotent stem cells, which means that they have the capacity to develop into multiple specialized cell types present in a tissue. They play an important role in cell therapies and are preferred over other types of stem cells, especially in neurodegenerative diseases (NNDs), due to their abilities, that include: multilinear differentiation into neural cells, secretion of neurotrophic factors and capacity to release antiinflammatory and angiogenic cytokines to repair damaged tissues.
Umbilical Cord Mesenchymal Stem Cells
Human umbilical cord is one of the best sources of MSCs since its collection is noninvasive and effortless, and MSCs from this source have low levels of human leukocyte antigen, low chance of tumorigenesis and high capability of proliferation.
Umbilical cord derived MSCs (UC-MSCs) are being widely used in neurodegenerative diseases. We will discuss some of the conditions that are being treated with these types of cells.
AD is a progressive NDD and is the leading cause of dementia. There were 46.8 million people worldwide living with AD and other forms of dementia in 2015 and this number is estimated to triple by 2050.
According to the 2016 Alzheimer’s Association’s Report, there is a new case of AD every 66 s in the USA. AD is caused by progressive accumulations of the amyloid-beta (Aβ plaques) outside neurons in the brain, twisted strands of the tau protein (tangles) inside neurons, neuronal apoptosis and synapse loss so the goal to treat AD is to ameliorate these pathogenesis.
There is no definite treatment for this disorder, but stem cell therapies have highlighted a new way to treat and cure AD via various mechanisms. Numerous studies and clinical trials on UC-MSCs transplantation have been done with satisfying results.
A reduction of Aβ plaques was observed in nearly all studies using UC-MSCs in animal models.
A study by Xie and colleagues worked on Warthon’s jelly MSCs and reported that the treatment dramatically decreased Aβ deposition. In another study in 2018, Li et al., found that autophagy plays an important role in the degradation of amyloid precursor protein (APP) and presenilin 1 (PS1), which are essential to produce Aβ plaques.
Cell apoptosis and synaptic dysfunction are also noticeable, resulting in cognitive impairment in AD. UC-MSCs transplantation ameliorated apoptosis and moreover, Wang et al., suggested that injecting resveratrol along MSCs reached better results than injection only stem cells.
PD is the second most common NDD following Alzheimer. There were over 6 million people living with PD in 2016 and it is estimated that this number will reach 17 million by 2031. It is more common in the elderly at around the age of 60 and men are more likely to have PD than women.
The condition causes a deterioration of nerve cells-producing dopamine (DA) in the extrapyramidal tract of the midbrain. It is a progressive disease that causes rigidity of muscles, tremors and changes in speaking and gait due to lack of dopamine, which is a chemical messenger that sets the communication between the substantia nigra and the basal ganglia to control the body movements.
Numerous studies have shown that hUC-MSCs are able to differentiate into DAergic cells or protect them from degeneration.
In a study in 2013, the potential of differentiated and undifferentiated hUC-MSCs in treatment of PD was examined compared to bone marrow (BM)-MSCs. In Parkinsonian rats, the group that received differentiated hUC-MSCs had much better alleviated symptoms of PD than two other groups. Longer survival of hUC-MSCs than BM-MSCs also notes that they represent a more beneficial choice in PD therapy.
Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) or Lou Gehric’s disease is a progressive, chronic NDD in which muscles responsible for voluntary movements start becoming weak and dysfunctional. Its primary symptoms are muscle trembling, weakening and roughness. Muscles also become thinner and moving them becomes difficult in a way that it even gets hard for the patient to speak.
Two to five years after diagnosis of ALS, most cases die due to respiratory failure. People who get involved with this disease are mostly between the age of 40–75 and two people per 100,000 get ALS every year.
The pathogenesis of this disease is the destruction of motor neurons in the brain and spinal cord due to mutation in SOD1.
In 2017 a study using UC-MSCs, with the aim of promoting stem cell migration, repeated injections were done. As results they indicated that significant motor neuron protection was observed in the spinal cord and the microglial activity and proinflammatory cytokines reduced.
A group of researchers from Poland performed a study using Warthon’s jelly umbilical cord derived mesenchymal stem cells. The study involved 67 patients with ALS and received 3 intrathecal injections of MSCs every 2 months. They found that the median survival time increased two-fold in all groups of patients and that these type of MSCs are safe and effective in some ALS patients, regardless of the clinical features and demographic factors, excluding sex. The saw that the female sex and a good therapeutic response to the first administration of cells are significant predictors of efficacy following further administrations.
Multiple sclerosis (MS) is an autoimmune NDD and is characterized by progressive inflammation and demyelination in the CNS. The autoreactive T lymphocytes cross the blood–brain barrier and secrete inflammatory mediators in the CNS, which result in oligodendrocytes destructions and formation of multiple plaques.
These damages are observed mostly in the optic nerves, periventricular white matter and spinal cord. Genetic and environmental issues influence the risk of developing the disease. Classic symptoms include motor weakness, paresthesias, impaired vision, double vision, dysarthria, intention tremor and ataxia.
Statistics show that about 2.5 million individuals, mainly ages between 20 and 40 suffer from MS around the world and the percentage is doubled in females.
The first study using hUC-MSC in MS was a case report in 2009 that transplanted stem cells intrathecal and intravenously to a 55-year-old woman who was suffering from primary progressive MS and severe numbness. Five-month postinjection, a reduction of thee points was observed in the Expanded Disability Status Scale (EDSS) score and symptoms alleviated.
Some clinical studies had applied MSC transplantation to MS patients that displayed immunomodulation, remyelination and promotion in MS recovery while no adverse reactions were reported.
Riordan et al. in 2018 studied clinical feasibility of UC-MSCs. Twenty subjects were enrolled in this study. The subjects received seven intravenous infusions of stem cells over 7 days. Efficacy was assessed at baseline, 1 month and 1 year after treatment. They reported that the intravenous infusion of UC-MSCs over several days is safe in subjects with MS. Additionally, UC-MSCs infusions may hold benefits, since this small study group saw improvement in bladder, bowel, sexual dysfunction, walking, upper extremity physical function, energy and fatigue, general perspective of a positive health change and improved quality of life, and MRI lesions.
Cerebral palsy (CP) is a common nonprogressive group of disorders following injuries to the developing brain that affects posture, movement and muscle tones in childhood. The symptoms are accompanied by difficulties in cognition, speaking, perception and sensation.
Statistics show that one to five cases out of each 1000 live birth face neonatal CP and about 7 million people suffer from CP worldwide.
Three cases of 4-, 5- and 6-year-old children with CP are reported who received hUC-MSC transplantation three, seven- and four-times, respectively. All showed significant improvements in disease symptoms and no serious side effects, except for a temporary mild fever or back pain, were noted during and after the treatment.
Autism Spectrum Disorder
Autism is a heterogeneous incurable neuronal disorder that is characterized by repetitive behavioral and social communication deficits and many children experience loss of skills and abilities indicating the cell degeneration in this disorder. Autism is more common in men that women and frequently happens in children before the age of 3 years.
A study by Lv et al., used a combination of UC-MSCs and cord blood mononuclear cells. They divided their subjects into three groups, one group received only CBMNCs and the other one combination of CBMNCs and hUC-MSCs and a control group. The results presented the highest reduction of childhood autism rating scale in the combination group by about 17 points at 24 weeks post-treatment, and in addition to no adverse reactions, better behavioral recovery was observed in this group.
Conclusions and Stem Cell Therapies at Zignagenix
MSCs have shown a promising potential in the therapy of neurodegenerative conditions due to their multiple capabilities, such as neuroprotection, immunomodulation and differentiation. Umbilical cord derived MSCs are easily obtained with no invasive procedures needed and with low immunogenicity.
At our clinic, we use Umbilical cord-derived Mesenchymal stem cells from Wharton’s jelly tissue.
Following different research studies, one of the best ways to deliver stem cells to the central nervous system is by performing an intrathecal injection. At the clinic, a physician specializing in Anesthesiology with years of experience in the field will perform an intrathecal injection with mesenchymal stem cells. This way, they can travel directly from the cerebrospinal fluid to the brain and the affected areas. Also, an intravenous infusion will be performed with a high dose of mesenchymal stem cells and exosomes to boost the therapeutic effect and increase the anti-inflammatory and regenerative properties of the cells.
Samira Reyhani, Bahareh Abbaspanah, Seyed Hadi Mousavi. Umbilical cord-derived mesenchymal stem cells in neurodegenerative disorders: from literature to clinical practice. 2020. Reg Med. https://doi.org/10.2217/rme-2019-0119.