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Table 2 Summary of applications of MSCs in ASD

From: Neuroinflammation in autism spectrum disorders: potential target for mesenchymal stem cell-based therapy

Type of MSCs/route of administration

Type of study

Key findings

References

MSC-CM/in vitro co-culture

Preclinical/primary and BV2 microglia cultured in MSC-CM

Activated microglia cultured in MSC-CM showed immunomodulatory effects of MSC-CM on microglia mediated through paracrine effects

[74]

MSC-MVs/in vitro co-culture

Preclinical/primary and BV2 microglia co-cultured with MSC-MVs

Activated primary and BV2 microglia co-cultured with MSC-MVs showed inhibition of upregulation of proinflammatory markers and suppression of phosphorylation of c-Jun N-terminal kinases and p38 MAP kinase

[75]

BM-MSCs/intracerebroventricular transplantation

Preclinical/BTBR mice

When compared with sham-treated mice, BM-MSC-treated mice showed behavioural and cognitive improvements, increased BNDF proteins in brain tissues and neurogenesis in the hippocampus

[76]

MSC-exo/intranasal route

Preclinical/BTBR mice

When compared with saline-treated mice, MSC-exo treated mice showed behavioural improvements. Effects of MSC-exo were mediated by membrane proteins

[78]

MSC-exo/intranasal route

Preclinical/Shank3B KO mice

Mice treated with MSC-exo showed symptom improvements, ability of MSC-exo to cross the BBB and increased RNA expression of GABA Rb1 receptors in frontal cortex

[79]

hUC-MSC-exo/intranasal route

Preclinical/offspring of valproic acid treated mice

Offspring of mice treated with intranasal MSC-exo showed behavioural improvements and penetration of MSC-exo in brain tissues

[80]

Human CBMNCs and UCMSCs/intravenous and intrathecal routes

Clinical/Phase I/II study

Both CBMNCs and UCMSCs were safe and efficacious in children with ASD (n = 37; 3–12 years). Combined UCMSCs and CBMNCs transplantation showed greater therapeutic effects than CBMNCs transplantation alone

[81]

Allogeneic hCT-MSCs/IV infusions

Clinical/Phase I study

Improvements in clinical and psychological outcomes (n = 12; 4–9 years). Presence of new anti-HLA Ab did not show clinical manifestations

[82]

Human allogeneic UC-MCS/intravenous route

Clinical/case study

Improvements in clinical outcomes and communication abilities with no serious adverse effects in two children

[83]

  1. ASD autism spectrum disorders, Anti-HLA Ab anti-HLA antibodies, BBB blood–brain barrier, BM-MSCs bone marrow-derived mesenchymal stem cells, BNDF brain-derived neurotrophic factor, CBMNCs cord blood mononuclear cells, GABA gamma-aminobutyric acid, hCT-MSCs human cord tissue-derived mesenchymal stromal cells, hUC-MSCs human umbilical cord-derived mesenchymal stem cells, MAP mitogen-activated protein, MSC-CM mesenchymal stem cell conditioned medium, MSC-exo mesenchymal stem cell-derived exosomes, MSC-MV mesenchymal stem cell-derived microvesicles