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Table 1 Native MSC therapy in preclinical models of common neurodegenerative diseases

From: Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects

Condition

Model

Cell source

Administration route

Result

References

AD

APP/PS1 mice

BM

Intraventricular

Restoring cognitive deficits by upregulation of miR-146a and downregulation of NF-κB

[105]

AD

SAMP8 mice

UC

intraperitoneal

Restoring cognitive deficits mediated by HGF in the AD hippocampus following stimulation of cMet/AKT/GSK3β axis

[61]

AD

3xTg mice

UC

Intravenous

Improving the MSCs engraftment and neural recovery by combination therapy with resveratrol

[101]

AD

Rat

ESC

Intraarterial

Suppressing Aβ-induced cell death in the hippocampus in association with provoking the autophagolysosomal clearance of Aβ

[189]

AD

Rat

BM

Intravenous

Attenuation of memory and cognition impairment by melatonin-pretreated MSCs

[103]

AD

Rat

AT

Intravenous

Improving the learning, memory, and cognition by melatonin-pretreated MSCs

[102]

AD

3xTg mice

BM

Intraventricular

Inspiring a population of proliferating cells in the SVZ

[190]

AD

3xTg mice

BM

Intravenous

Alleviating the Tau phosphorylation and inflammation with no effect on Aβ-42 levels

[191]

AD

Amyloid β mice

UCB

Intracerebral

Restoring the learning, memory, and cognition

[192]

AD

5xFAD mice

BM

Intraventricular

Attenuation of learning impairment

[193]

AD

Amyloid β mice

BM

Intracerebral

Reduction in Aβ aggregates and supporting synaptic transmission

[194]

AD

APP/PS1 mice

UC

Intrathecal

Improving the endogenous adult hippocampal neurogenesis as a result of GDF-15 secretion

[62]

AD

5XFAD mice

WJ

Intrahippocampal

Promoting the proteasome activity and reducing the accumulation of ubiquitin-conjugated proteins mediated by MSC-secreted agouti-related peptide (AgRP)

[195]

PD

MPTP mice

BM

Intracranial

Marked synergistic impacts between electric stimulation and MSCs due to the enhanced levels of dopamine and reduced pro-inflammatory cytokines, restoring behavioral function

[196]

PD

MPTP mice

AT

Intravenous

Inducing alteration in dopamine transporter expression, promoting BDNF and GDNF levels in the striatum

[63]

PD

6-OHDA rat

BM

Intracarotid

No effect on motor impairment

[116]

PD

6-OHDA rat

BM

NA

Synergistic effect between G-CSF and MSCs by downregulation of pro-inflammatory cytokines, stimulating antioxidant enzymes and finally augmenting

[123]

PD

MPTP monkey

Endometrial

Intrastriatal

Enhancing the frequency of TH positive cells and also dopamine metabolite concentrations

[45]

PD

MPTP mice

Endometrial

Intracranial

Improvement of dopamine production

[108]

PD

6-OHDA rat

WJ

Intravenous

Restoring dopaminergic neurons and enhancement of the levels of BDNF and NGF

[64]

PD

Rat

BM

Intravenous

Restoring rotational behavior and enhancing TH-positive cell

[65]

PD

Rotenone rat

HED

Intravenous

PD recovery by modifying the cholinergic synapses, calcium signaling pathways, and axon guidance

[197]

PD

6-OHDA rat

BM

Intrastriatal

Improving the viability of striatal/nigral dopaminergic terminals concomitant with inducing neurogenesis in SVZ

[198]

PD

MG-132 rat

BM

Intravenous

Neuroprotective effects on dopaminergic neurons

[199]

PD

6-OHDA rat

BM

Intranigral

Differentiation into nestin-, neuron-specific enolase-, and GFAP-positive cells

[46]

PD

6-OHDA rat

BM

Intrastriatal

Partial rescue of dopaminergic pathway

[200]

PD

MPTP mice

BM

Intravenous

Neuroprotective effects on dopaminergic neurons, reducing blood–brain barrier damage and downregulation of neuroinflammation

[201]

PD

Rotenone rat

BM

Intranasal

Improved locomotor functions

[202]

ALS

SOD1G93A mice

BM

Intravenous

Enhancing motor neuron frequency, and reducing denervation and myofibril atrophy

[203]

ALS

SOD1G93A mice

BM

Intravenous

Augmenting pathological scores

[136]

ALS

SOD1G93A mice

AT

Intravenous

Marked and durable impacts on motor function by improving bFGF and VEGF levels

[135]

ALS

SOD1G93A mice

NA

Intraventricular

Intraspinal

Intraspinal administration of MSCs has superiority over intraventricular injection in terms of restoring functional activity

[137]

ALS

SOD1G93A mice

BM

Intraspinal

Intravenous

Prolonged lifespan of treated mice

[133]

ALS

SOD1G93A rat

BM

Intracerebospinal

Prolonged lifespan induced by chimerization of the astroglial population in the lumbar spinal cord following stem cell transplantation

[139]

ALS

SOD1G93A mice

Muscle

Intraventricular

Sustained motor function

[134]

ALS

SOD1G93A mice

BM

Intraspinal

Sustained motor function and dampened neuroinflammation

[204]

ALS

SOD1G93A rat

BM

Intrathecal

Neuroprotective effects on motor neurons and neuromuscular junctions by downregulation of apoptosis, necroptosis, and autophagy pathway

[138]

ALS

SOD1G93A mice

UCB

Intramuscular

Downregulation of inflammation by targeting iNOS/NO signaling pathway

[58]

ALS

SOD1G93A mice

UC

Intraventricular

Downregulation of pro-inflammatory cytokine levels, upregulation of anti-inflammatory cytokine levels, and promotion of IGF-1 levels in the lumbar spinal cord

[59]

ALS

SOD1G93A mice

Amniotic

Intravenous

Prolonged survival, restored motor functions, and suppressed neuroinflammation

[205]

HD

Transgenic mice

BM

Intrastriatal

Improving BDNF levels in the striatum

[127]

HD

Transgenic rat

BM

Intrastriatal

Co-transplanting MSCs with NSCs led to more favorable behavioral sparing

[206]

HD

Transgenic mice

BM

Intranasal

Improved therapeutic benefits by MSCs preconditioning with mood stabilizers lithium and valproic acid

[131]

HD

Transgenic mice

UC

Intravenous

Reducing astrogliosis, and neuroinflammation by downregulation of NF-κB p65 phosphorylation

[207]

HD

3-NP rat

UC

intrastriatal

Improving motor function, enhancing striatal volume, and dendritic length in striatum mediated through the production of VEGF and GDNF by MSCs

[66]

HD

QA rat

BM

Intrastriatal

Reduced striatum atrophy

[208]

HD

3-NP rat

BM

Intrastriatal

Improvement in BDNF, collagen type I, and fibronectin levels in brain

[128]

HD

Transgenic mice

UC

Intrastriatal

Partial improvement of spatial memory

[209]

HD

QA rat

BM

Intravenous

Amelioration of motor and cognitive impairment

[210]

  1. MSC, Mesenchymal stromal cells; AD, Alzheimer’s disease; PD, Parkinson’s disease; ALS, amyotrophic lateral sclerosis; HD, Huntington’s disease; BM, bone marrow; UC, umbilical cord; UCB, umbilical cord blood; AT, adipose tissue; ESC, embryonic stem cell; WJ, Wharton’s jelly; 6-OHDA, 6-hydroxydopamine; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3-NP, 3-nitropropionic acid; QA, quinolinic acid; NF-kB, nuclear factor kappa B; HGF, hepatocyte growth factor; GSK-3β, glycogen synthase kinase-3β; Aβ, amyloid beta peptide; SVZ, subventricular zone; GDF-15, growth/differentiation factor-15; GDNF, glial cell line-derived neurotrophic factor; BDNF, brain-derived neurotrophic factor; TH, thymidine hydroxylase; G-CSF, granulocyte colony-stimulating factor; NGF, nerve growth factor; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; iNOS, inducible nitric oxide synthase; IGF-1, insulin like growth factor-1; GFAP, glial fibrillary acidic protein; NSCs, neural stem cells; miRs, microRNAs