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Review Open Access

Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)

  • Authors:
    • Zhaojian Sun
    • Nouman Amjad
    • Majid Muhammad
    • Zhiyuan Li
  • View Affiliations / Copyright

    Affiliations: GMU‑GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Center for Cell Lineage Technology and Engineering, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, Guangdong 510530, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 60
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    Published online on: January 13, 2026
       https://doi.org/10.3892/ijmm.2026.5731
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Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by marked genetic heterogeneity and diverse environmental influences. Current treatment approaches focus on symptom management, with only a limited number of effective interventions targeting the underlying causes. Recently, mesenchymal stem cells (MSCs) and their derived exosomes (MSC‑Exos) have emerged as promising candidates for ASD therapy owing to their potent immunomodulatory, neuroprotective and targeted delivery properties. The present review discusses the functions of MSC‑Exos and their potential use in ASD. MSC‑Exos improve neuroinflammation, enhance synaptic plasticity and restore neural network function by delivering bioactive molecules. Moreover, MSC‑Exos exhibit a low immunogenicity, a favorable safety profile and scalability for clinical production. Despite promising results however, clinical trials continue to face challenges, particularly in standardizing the isolation, characterization, dosing and administration routes of exosomes. In addition, significant challenges persist in production processes, quality control and the elucidation of the mechanisms of action. In conclusion, MSC‑Exos represent a groundbreaking, cell‑free therapeutic strategy with substantial potential to target the core pathophysiology of ASD. In the future, multicenter randomized controlled trials and interdisciplinary collaborations will be crucial for translating preclinical findings into the development of effective and transformative therapies for ASD. 

View Figures

Figure 1

Interactions between microglia,
astrocytes, and neurons in the autism spectrum disorder-affected
brain. M1 microglia and A1 astrocytes release pro-inflammatory
cytokines (e.g., TNF-α, IL-1β and IL-6) that amplify
neuroinflammation and induce synaptic damage. In contrast, M2
microglia and A2 astrocytes secrete anti-inflammatory and
neurotrophic factors (e.g., IL-10, TGF-β, BDNF and CNTF), promoting
synaptic repair, BBB stability and homeostasis. Arrows indicate
intercellular regulatory pathways. The authors created this figure
referencing multiple sources (40-56,62-68,74-82). TNF-α, tumor necrosis factor-α;
IL, interleukin; TGF-β, transforming growth factor β; BMP, bone
morphogenetic protein; CNTF, ciliary neurotrophic factor; iNOS,
inducible nitric oxide synthase; BBB, blood brain barrier.

Figure 2

Sources of MSCs. Adult MSCs can be
derived from bone marrow, adipose tissue, peripheral blood,
skeletal muscle, and dental pulp. Perinatal MSCs are typically
harvested from the placenta, umbilical cord, cord blood, amniotic
fluid, and amniotic membrane. This figure was created based on data
or concepts adapted from the study by Brown et al (88), but was drawn and designed by the
authors. MSCs, mesenchymal stem cells.

Figure 3

Biogenesis, molecular contents and
mechanisms of MSC-derived exosomes in ASD therapy. (Left panel)
MSC-derived exosomes originate from endosomal pathways. They
encapsulate proteins, mRNAs and miRNAs. (Top right panel) These
exosomes interact with neurons, microglia and astrocytes,
modulating synaptic plasticity, microglial polarization, and
astrocyte phenotype to alleviate neuroinflammation associated with
ASD. (Bottom right panel) Exosomal surface and cargo proteins
include CD63, CD81, CD9, CD73, flotillin-1/2, TSG101, Annexin
A1/A2, galectin-1, neurotrophic factors and molecular chaperones.
The authors created a figure referencing multiple sources (119-123,133-139,141-143). ASD, autism spectrum disorder;
MSCs, mesenchymal stem cells.
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Copy and paste a formatted citation
Spandidos Publications style
Sun Z, Amjad N, Muhammad M and Li Z: <p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>. Int J Mol Med 57: 60, 2026.
APA
Sun, Z., Amjad, N., Muhammad, M., & Li, Z. (2026). <p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>. International Journal of Molecular Medicine, 57, 60. https://doi.org/10.3892/ijmm.2026.5731
MLA
Sun, Z., Amjad, N., Muhammad, M., Li, Z."<p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>". International Journal of Molecular Medicine 57.3 (2026): 60.
Chicago
Sun, Z., Amjad, N., Muhammad, M., Li, Z."<p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>". International Journal of Molecular Medicine 57, no. 3 (2026): 60. https://doi.org/10.3892/ijmm.2026.5731
Copy and paste a formatted citation
x
Spandidos Publications style
Sun Z, Amjad N, Muhammad M and Li Z: <p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>. Int J Mol Med 57: 60, 2026.
APA
Sun, Z., Amjad, N., Muhammad, M., & Li, Z. (2026). <p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>. International Journal of Molecular Medicine, 57, 60. https://doi.org/10.3892/ijmm.2026.5731
MLA
Sun, Z., Amjad, N., Muhammad, M., Li, Z."<p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>". International Journal of Molecular Medicine 57.3 (2026): 60.
Chicago
Sun, Z., Amjad, N., Muhammad, M., Li, Z."<p>Harnessing MSC‑derived exosomes to modulate the pathophysiology of ASD: Recent advances and therapeutic implications (Review)</p>". International Journal of Molecular Medicine 57, no. 3 (2026): 60. https://doi.org/10.3892/ijmm.2026.5731
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