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Epidemiology International Journal Research Article 9 min read

Stem Cells Applications in Neurodegenerative Diseases

Yang J*
* Corresponding author
ISSN: 2639-2038  10.23880/eij-16000267  Received: September 12, 2023  Published: October 31, 2023
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Keywords
Stem Cells Parkinson's Disease Preclinical Application Clinical Application Neurodegenerative Diseases

Introduction

It is reported that there are 164.5 million Chinese citizens aged above 60 years old and 26 million elderly people aged above 80 years old in China in 2019, the proportion of the elderly population will increase to 26% of the total population by 2050; and the number of neurodegenerative diseases has correspondingly increased with the severity of global aging [1]; statistical results demonstrated there was 50 million people with dementia in the world, and the number will be increase to 150 million, in fact, 50–70% people with dementia will deteriorate to AD [2]; Shige Qi, et al. investigated and predicted that The prevalence of PD in China was 1.37% in the elderly population aged above 60 years old, this indicated that there will be 3.62 million PD patients in China [3]. Those data demonstrated that because lack of the effective treatment, the medical burden and economic burden of neurodegenerative diseases is on the rise globally.

Neurodegenerative diseases are a kind of disease in which nerve cells or nerve related cells are damaged, usually, nerve cells are almost unable to regenerate in adult, this undoubtedly increases the difficulty to cure for neurodegenerative diseases. Stem cell technology as one of the greatest inventions of the 21st century, because its superior advantages including neural differentiation ability [4], migration and homing capabilities [5], and secreting the many kinds of neurotrophic factors [6], stem cells are becoming an ideal treatment method for neurodegenerative diseases. Here, we summarized the recent progress on the preclinical applications and clinic applications of stem cells in the neurodegenerative diseases, discuss the existing the problems and challenges in applications, which may provide some ideas for the further study of stem cells in neurodegenerative diseases.

The Preclinical Applications of Stem Cells in Neurodegenerative Diseases

Because of the diversity of stem cell types, the diversity of neurodegenerative diseases, diversity of animal models, and the diversity of administration methods, there are many preclinical applications of stem cells in neurodegenerative diseases have been reported in the past twenty years. Those evidences demonstrated no matter pluripotent or unipotent stem cells exhibit good therapeutic advantages in neurodegenerative diseases. The following table was a simple summary we collected for preclinical applications of stem cells in neurodegenerative diseases.

Cell LinesTypes Of Animal
Models		AnimalsTypes Of
Neuro
degenerative
Diseases		Administration
Methods		EffectsThe Underlying
Mechanism		Refe-
rences
BMMSCs6-hydroxydopamine
(6-OHDA) PD model		nine-week-
old Wistar
Han male
rats		PDsurgical
administration		Improve 6-OHDA PD
motor and histological
deficits		secreted several
kinds of factors		[7]
hNSCsAPP/PS1 transgenic
mice		/ADintranasal
Transplantation		Improve
neuroinflammation,
cholinergic
dysfunction, and
pericytic and synaptic
loss, and enhance
adult hippocampal
neurogenesis		hNSCs
differentiated
into cholinergic
neurons,and
secrete a variety
of neurotrophic
factors		[8]
human
neural
crest-
derived
nasal
turbinate
stem cells,
human
bone
marrow
MSCs		5×FAD transgenic
mouse model of AD		16 weeks,
male mice		ADInjection
administration		Reduce the Aβ plaque
deposition and Aβ levels;
regulate inflammatory
microglial status;
improve the cognitive
impairment; increase
neuronal survival		differentiated
into neuron;
modulation of
autophagy		[9]
human
NSCs		The 1-methyl-4-
phenyl-1,2,3,6-
tetrahydropyridine
(MPTP)-induced
C57BL/6 PD mice		C57BL/6
mice		PDnasally
administered		hNSCs were mainly
distributed in the
striatum, cortex, and
hippocampus		/[10]
hiPSC6-hydroxydopamine
(6-OHDA) PD model		RAG2 KO
mice		PDInjection
administration		Long-Term
Functional Motor
Recovery;Reconstruction
of the Nigrostriatal
Pathway and Innervation
of the Striatum		differentiated
into mDA
neurons		[11]

Table 1: The summary of preclinical applications of stem cells in neurodegenerative diseases

  • Seven– eightweek-old male and female
  • NOG mice hiPSC
  • 6-OHDA-lesioned rats;MPTP-treated monkeys
  • PD
  • Injection administration
  • Functional behavior improvement hESCs
  • 6-hydroxydopamine
  • (6-OHDA) PD model rats
  • PD
  • Injection administration
  • Functional behavior improvement human immature dental pulp stem cells (hIDPSC)
  • 3-nitropropionic acid (3-NP) HD model
  • 8 weeks male
  • Wistar rats
  • HD intravenous transplantation improve BDNF expression and DARPP32 and D2R expression
  • 8 weeks female
  • Sprague–
  • Dawley rats hESCs
  • Viral vector HD model
  • HD
  • Injection administration
  • Improve motor dysfunctions hNSCs
  • HD fragment model
  • R6/2 mice; Q140
  • Knockin Mice
  • /
  • HD
  • Bilateral intrastriatal injections improved motor and late-stage cognitive impairment
  • 9 or 14 weeks old
  • SOD1G93A mice
  • BMSCs lumbar portion of the spinal cord of
  • SOD1G93A mice
  • ALS
  • Injection administration had only a transitory effect
  • /
  • [17] protects motor neurons and reduces glial activation
  • ADSCs transgenic
  • SOD1G93A mice
  • /
  • ALS
  • Injection administration

Table 2: The summary of preclinical applications of stem cells in neurodegenerative diseases

The Clinical Applications of Stem Cells in Neurodegenerative Diseases

Many scientists have demonstrated the feasibility of stem cells in treatment of neurodegenerative diseases from multiple perspectives and mechanisms, and with the further research and the openness of policies in various countries, there are several preclinical applications research of stem cells in neurodegenerative diseases enter into the clinical research stage, and achieved good clinical results in the recent five years. For example, Jeffrey S. Schweitzer, et al. obtained the iPSCs from an idiopathic Parkinson’s disease patient, and implanted autologous iPSCs derived midbrain dopaminergic neurons into an elderly man aged 69-year- old with a 10-year history of progressive idiopathic PD, found that the symptoms of the patient were improved after implantation for 18-24 months [19]. Cudkowicz ME, et al. [20] recruited nine Alzheimer’s disease patients at mild-to-moderate stage and treated the patients by three repeated injections of hUCB-MSCs, the results of clinic and physiological and biochemical indexes found that the hUCB- MSCs application on AD patients at mild-to-moderate stage was safe and effective [20] and we summarized the clinical applications of stem cells in neurodegenerative diseases which have been published in pubmed in Table 2. The collected data demonstrated that the clinical applications of cell lines in neurodegenerative diseases were MSCs but not ESCs or iPS, the type neurodegenerative diseases was ALS but not PD or AD (Table 2).

Cell LinesTypes of Neuro
degenerative
Diseases		CountryObservation
Period		Clinical StageSide EffectsReferences
MSC‐
neurotrophic
factors		ALSUS28 weeksphase III
clinical trial		did not reach statistical
significance on the
primary endpoint		[21]
bone marrow
MSC		ALSIsrael7-8 monthsphase II clinical
trial		Weakness, Fatigue,
Headache		[22]
ADMSCsSMAIran24 monthsphase I clinical
trial		/[23]
hUCB-MSCsPDKorea36 monthsphase I clinical
trial		Fever, Nausea,
Headache		[20]
hNSCsALSNovara, Italy60 monthsphase I clinical
trial		Pain[24]
MSCsMSAUS12 monthsphase I /II
clinical trial		Urinary tract infection,
Headache, pain		[25]
MSC-
neurotrophic
factors		ALSUS6 monthsphase II clinical
trial		Headache, pain,
Pyrexia, Arthralgia		[26]

Table 3: The summary of clinical applications of stem cells in neurodegenerative diseases.

The Application Limitations of Stem Cells in Neurodegenerative Diseases

Recently, the preclinical and clinic applications of stem cells in neurodegenerative diseases have make the great progress, and stem cells exhibit the huge advantages in treatment of neurodegenerative diseases. But there are several problems should be considered:

  1. The source of stem cells. Stem cells can be divided into ESCs, iPS, NSCs, BMMSCs, UCB-MSCs according to the different classification methods, how to accurately define and differentiate the many kinds of stem cells and how to define the quality standards for stem cells are very important for stem cells clinical application, obtaining a large number of consistent characteristics and consistent quality stem cells that meet clinical usage standards is the key to the clinical application of stem cells
  2. The differentiation and induction stem cells. Currently, there are many kinds of differentiation methods of stem cells, how to make sure orderly and consistent induction efficiency and how to obtain highly consistent stem cell derived functional neural cells, it is also a problem should be solved
  3. The tumorigenicity of ESCs or iPS. Many articles have reported that ESCs or iPS could result in tumorigenicity because the pluripotency of ESCs or iPS, and it also become a huge obstacle for ESCs or iPS applications
  4. Animal models of neurodegenerative diseases. The establishment of animal models is to maximize the simulation of human diseases, in fact, there is a significant gap in the existing animal models of neurodegenerative diseases in humans, this is also a huge obstacle for stem cells applications in neurodegenerative diseases
  5. Formulation and update of policies and relevant laws and regulations related to stem cells.

So far, stem cell related laws and regulations are also big obstacle for stem cells applications. For example, many European and American countries have established policies that prohibit stem cell related research, greatly limiting the applications of stem cells.

Conclusion

Although there are still many significant shortcomings in the basic research, preclinical and clinic applications of stem cells, with the research progress of regenerative medicine, the stem cells applications in neurodegenerative diseases will achieve great success in the future.

Competing Interests

The authors declare to have no conflicts of interest.

References

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@article{yang2023,
  title   = {Stem Cells Applications in Neurodegenerative Diseases},
  author  = {Yang J},
  journal = {Epidemiology International Journal},
  year    = {2023},
  volume  = {7},
  number  = {4},
  doi     = {10.23880/eij-16000267}
}
Yang J (2023). Stem Cells Applications in Neurodegenerative Diseases. Epidemiology International Journal, 7(4). https://doi.org/10.23880/eij-16000267
TY  - JOUR
TI  - Stem Cells Applications in Neurodegenerative Diseases
AU  - Yang J
JO  - Epidemiology International Journal
PY  - 2023
VL  - 7
IS  - 4
DO  - 10.23880/eij-16000267
ER  -