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Intranasal delivery of human Wharton’s jelly-derived mesenchymal stem cells alleviates Aβ-induced Alzheimer’s symptoms in rat models by regulating neurotrophic and apoptotic factors

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Abstract

Alzheimer's disease (AD) is the most common cause of dementia in adulthood, followed by cognitive and behavioral deficits. Today, mesenchymal stem cell (MSC)-based therapy is a suitable therapeutic option to improve regenerative medicine approaches against neurodegenerative disorders, including AD. This study aimed to investigate the effects of human Wharton’s jelly-derived MSCs (WJ-MSCs) on AD-like rat models (rats treated with amyloid beta 1-42 (Aβ1-42)) by evaluating the expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), as well as the expression of apoptotic factors such as B-cell lymphoma 2 (BCL2, an anti-apoptotic factor to inhibit apoptosis) and BCL2-associated X protein (BAX, a pro-apoptotic factor to regulate apoptosis). After treatment of AD rat models with WJ-MSCs, behavioral tests (i.e., passive avoidance and Morris water maze) showed cognitive improvements, and amelioration of cells in the CA1 area of the hippocampus was detected by cresyl violet staining. Additionally, real-time polymerase chain reaction (RT-PCR) of the hippocampus indicated an increase in the expression level of the BDNF, NGF, and BCL2 genes and a decrease in the expression level of the BAX gene. Overall, the WJ-MSCs improved the cognitive function in AD rat models by increasing the neurotrophic and anti-apoptotic factors and decreasing the pro-apoptotic factor.

Graphical Abstract

This graphical abstract depicts the process of isolating mesenchymal stem cells (MSCs) from human Wharton’s jelly (WJ) and their subsequent use in an Alzheimer’s disease (AD) rat model. The left side of the image illustrates the steps involved in isolating MSCs from WJ. The right side of the image shows how AD rat models are generated under stereotaxic injection of Aβ. In the middle, intranasally administration of MSCs is shown and then how their effects are evaluated using behavioral tests, nissl staining, and RT-qPCR.

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Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The authors gratefully acknowledge the financial support of the Cellular and Molecular Research Center (CMRC) of IUMS (94-05-117-27524) and the Iran National Science Foundation (INSF) for funding this work through a grant (95849005). Experiments were performed at the Cellular and Molecular Research Center (CMRC) and IUMS Core Laboratory (ICL), Tehran, Iran.

Funding

This work was supported by grants from Iran University of Medical Sciences (IUMS) (97-4-75-13504) and Iran National Science Foundation (INSF).

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Author notes

  1. Farshid Ghiyamihoor and Ebrahim Eslami have contributed equally to this work.

Authors and Affiliations

  1. Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

    Ebrahim Eslami & Marjan Sadr

  2. Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Farshid Ghiyamihoor

  3. Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran

    Marziyeh Ajdary

  4. Department of Physiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

    Sahar Hakimpour

  5. School of Dentistry, Central Tehran Branch, Islamic Azad University, Tehran, Iran

    Rana Mehdizadeh

  6. Reproductive Sciences and Technology Research Center, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran

    Ronak Shabani & Mehdi Mehdizadeh

  7. Department of Anatomical Sciences, Iran University of Medical Sciences, P.O. Box: 15875-1454, Tehran, Iran

    Ronak Shabani & Mehdi Mehdizadeh

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  1. Ebrahim Eslami
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Contributions

Conceptualization, Methodology, and Investigation [Ebrahim Eslami, Farshid Ghiyamihoor, Marjan Sadr, Marziyeh Ajdary, Sahar Hakimpour, Rana Mehdizadeh, Ronak Shabani, Mehdi Mehdizadeh]; Writing – original draft preparation [Farshid Ghiyamihoor]; Writing – Review and Editing [Ebrahim Eslami, Farshid Ghiyamihoor, Marjan Sadr, Marziyeh Ajdary, Sahar Hakimpour, Rana Mehdizadeh, Ronak Shabani, Mehdi Mehdizadeh]; Funding Acquisition and Resources [Mehdi Mehdizadeh]; Supervision, [Mehdi Mehdizadeh and Ronak Shabani]

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Correspondence to Ronak Shabani or Mehdi Mehdizadeh.

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All procedures performed in this study were in accordance with the ethical standards of the institutional research ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All procedures performed on animals were in accordance with the ethical standards of the IUMS (IR.iums.rec.1397.1299).

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Eslami, E., Ghiyamihoor, F., Sadr, M. et al. Intranasal delivery of human Wharton’s jelly-derived mesenchymal stem cells alleviates Aβ-induced Alzheimer’s symptoms in rat models by regulating neurotrophic and apoptotic factors. Neurosci Behav Physi (2024). https://doi.org/10.1007/s11055-024-01582-1

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