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Potential Plausible Role of Stem Cell for Treating Depressive Disorder: a Retrospective Review

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Abstract

Depression poses a significant threat to global physical and mental health, impacting around 3.8% of the population with a rising incidence. Current treatment options primarily involve medication and psychological support, yet their effectiveness remains limited, contributing to high relapse rates. There is an urgent need for innovative and more efficacious treatment modalities. Stem cell therapy, a promising avenue in regenerative medicine for a spectrum of neurodegenerative conditions, has recently garnered attention for its potential application in depression. While much of this work remains preclinical, it has demonstrated considerable promise. Identified mechanisms underlying the antidepressant effects of stem cell therapy encompass the stimulation of neurotrophic factors, immune function modulation, and augmented monoamine levels. Nonetheless, these pathways and other undiscovered mechanisms necessitate further investigation. Depression fundamentally manifests as a neurodegenerative disorder. Given stem cell therapy’s success in addressing a range of neurodegenerative pathologies, it opens the door to explore its application in depression treatment. This exploration may include repairing damaged nerves directly or indirectly and inhibiting neurotoxicity. Nevertheless, significant challenges must be overcome before stem cell therapies can be applied clinically. Successful resolution of these issues will ultimately determine the feasibility of incorporating stem cell therapies into the clinical landscape. This narrative review provides insights into the progress of research, potential avenues for exploration, and the prevailing challenges in the implementation of stem cell therapy for treatment of depression.

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Abbreviations

BDNF:

Brain-derived neurotrophic factor

GDNF:

Glial-derived neurotrophic factor

IL-1:

Interleukins-1

IL-6:

Interleukins-6

TNF-α:

Tumor necrosis factors-α

NF-κB:

Nuclear factor kappa-B

TLR-4:

Toll-like receptor4

DA:

Dopamine

DAMPs:

Damage-associated molecular patterns

NMDA:

N-methyl-d-aspartate

NMDAR:

N-methyl-d-aspartate receptor

MCP-1:

Monocyte chemotactic protein-1

GDF-15:

Growth differentiation factor-15

5-HT:

5-Hydroxytryptamine

GABA:

Gamma-aminobutyric acid

mGIN:

GABAergic interneurons

AD:

Alzheimer’s disease

PD :

Parkinson’s disease

HD:

Huntington’s disease

MRI:

Magnetic resonance imaging

MDD:

Major depressive disorder

ECT:

Electroconvulsive therapy

SVZ:

Subventricular zone

SGZ:

Subgranular zone

NTs:

Neurotrophins

FSLs:

Flinder sensitive line rats

ALS:

Amyotrophic lateral sclerosis

TLE:

Temporal lobe epilepsy

MS:

Multiple sclerosis

TLE:

Temporal lobe epilepsy

CNTF:

Ciliary neurotrophic factor

FGF-2:

Fibroblast growth factor 2

TrKB:

Tyrosine kinase receptor B

Jmjd3:

Jumonji domain-containing protein 3

NP:

Neuropathic pain

BIS:

Brain ischemic stroke

MSNs:

Medium spiny neurons

MNs:

Motor neurons

NTFs:

Neurotrophic factors

BBB:

Blood-brain barrier

VEGF:

Vascular endothelial growth factor

ESCs:

Embryonic stem cells

MSCs:

Mesenchymal stem cells

NSCs:

Brain-derived neural stem cells

iPSCs:

Induced pluripotent stem cells

hMSCs:

Human mesenchymal stem cells

hESC:

Human embryonic stem cells

ADSCs:

Adipose-derived mesenchymal stem cells

hUC‐MSCs:

Human umbilical cord‐derived mesenchymal stem cells

BMSCs:

Bone marrow–derived mesenchymal stem cells

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Acknowledgements

The authors would also like to thank the National Natural Science Foundation of China (NSFC), China Administration of Traditional Chinese Medicine, Heilongjiang Provincial Administration of Traditional Chinese Medicine, and Heilongjiang University of Traditional Chinese Medicine in China for their assistance.

Funding

This work was supported by the Research Project of Heilongjiang Traditional Chinese Medicine Administration (Grant Number: ZHY2022-110); Youth Program of the National Natural Science Foundation of China (Grant Number: 82205163); Chief Scientist of Qi-Huang Project of National Traditional Chinese Medicine Inheritance and Innovation “One Hundred Million” Talent Project (Grant Number: [2021] No. 7); National Famous Old Traditional Chinese Medicine Experts Inheritance Studio Construction Program of National Administration of TCM (Grant Number: [2022] No. 75); The Seventh Batch of National Famous Old Traditional Chinese Medicine Experts Experience Heritage Construction Program of National Administration of TCM (Grant Number: [2022] No. 76); and Heilongjiang Touyan Innovation Team Program (Grant Number: [2019] No. 5); This work was also supported by the Scientific Research Foundation of Heilongjiang University of traditional Chinese Medicine (Grant Number: 2019MS34) and Post-doctoral Research Start-up Project in Heilongjiang Province (Grant Number: LBH-Q21193).

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  1. Heilongjiang University of Chinese Medicine, Heping Road 26, Harbin, Heilongjiang, 150040, China

    Zhuo Chang, Qing-yi Wang, Lu-hao Li, Bei Jiang, Xue-ming Zhou, Hui Zhu, Yan-ping Sun, Xu-xu Tu & Hai-xue Kuang

  2. Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China

    Xue Pan

  3. First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China

    Wei Wang

  4. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China

    Chen-yue Liu

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Contributions

H-xK, ZC: conception and design, manuscript writing, administrative support, data analysis and interpretation, and final approval of the manuscript. ZC: manuscript writing and data analysis and interpretation. Q-yW, Y-pS: correction/touchup and interpretation. BJ, X-mZ: figure presentation and interpretation. XP, X-xT, L-hL: reference organization and data analysis and interpretation. H-xK: administrative support, and final approval of the manuscript. All authors have read and approved the article.

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Chang, Z., Wang, Qy., Li, Lh. et al. Potential Plausible Role of Stem Cell for Treating Depressive Disorder: a Retrospective Review. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03843-5

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