Neurotrauma and mesenchymal stem cells treatment: From experimental studies to clinical trials

Table 1 Summary of pre-clinical studies using mesenchymal stem cell for spinal cord injury

Animal	Lesion type	Cells source	Route of administration	Effects on CNS regeneration	Ref.
Rat	Contusion	Human mesenchymal precursor cells	Lesion site	Improvement in functional recovery and tissue sparing and reduction of cyst volume	[35]
Rat	Contusion	Human bone marrow-MSC	Lesion site , intracisternal, intravenous	Improvement in functional recovery	[36]
Rat	Hemisection	Bone marrow-MSC induced into Schwann Cells	Lesion site	Improvement in locomotor and sensory scores, axonal regeneration and remyelination	[37]
Rat	Contusion	Bone marrow-MSC	Lesion site , intravenous	Improvement in locomotor scores and NGF expression	[38-40]
Rat	Transection to the dorsal columns and tracts	Bone marrow-MSC, adipose derived-MSC	Lesion site	Improvement in locomotor scores, increased angiogenesis, preserved axons, decreased numbers of ED1-positive macrophages and reduced lesion cavity formation	[41]
Rat	Hemisection	Human umbilical cord-derived MSC	Lesion site	Suppress mechanical allodynia, and this effect seems to be closely associated with the modulation of spinal cord microglia activity and NR1 phosphorylation	[42,43]
Rat	Hemisection	Human bone marrow-MSC	Lesion site	Improvement in locomotor scores, shorter latency of somatosensory-evoked potentials and differentiation into various cells types	[44]
Rat	Hemisection	Bone marrow-MSC	Lesion site	Improvement in locomotor scores and reduced lesion cavity formation	[45]
Mouse	Compression	Bone marrow-MSC	Lesion site	Improvement in locomotor and sensory scores and reduced lesion volume	[46]
Rat	Contusion	Human bone marrow-MSC	Lesion site	Improvement in functional recovery, tissue sparing and reduction in the volume of lesion cavity and in the white matter loss	[35,47-49]
Rat	Contusion	Human umbilical cord-MSC	Lesion site	Improvement in functional recovery, reduction of the extent of astrocytic activation and increased axonal preservation	[50]
Dog	Compression	Bone marrow, adipose, Wharton’s jelly, umbilical cord derived-MSC	Lesion site	Improvement in functional recovery, increased numbers of surviving neurons, smaller lesion sizes and fewer microglia and reactive astrocytes in the epicenter of lesion	[51]
Rat	Compression	Bone marrow-MSC	Intravenous	Improvement in functional recovery, increase of NGF expression, higher tissue sparing and density of blood vessels	[52]
Rat	Contusion	Human umbilical cord-MSC	Lesion site	Improvement in functional recovery, endogenous cell proliferation and oligogenesis, and smaller cavity volume	[53,54]
Rat	Transection	Human-MSC	Lesion site	Improvement in functional recovery, increased amplitude of motor-evoked potentials, differentiation into neural cells	[55,56]
Rat	Contusion	Bone marrow-MSC	Lesion site	Improvement in functional recovery, preservation of axons, less scar tissue formation and increase in myelin sparing; higher levels of IL-4 and IL-3 and higher numbers of M2 macrophages, and reduction in TNF-α and IL-6 levels, and in numbers of M1 macrophages	[57-60]
Dog	Compression	Neural-induced adipose derived-MSC	Lesion site	Improvement in functional recovery and neuronal regeneration, and reduction of fibrosis	[61]
Mouse	Transection	Bone marrow-MSC	Lesion site	Improvement in functional recovery and neuronal survival, reduction of cavity volume and attenuation of inflammation, promotion of angiogenesis and reduction of cavity formation	[62-64]
Rat	Compression	Bone marrow-MSC	Lesion site	Improvement in functional recovery, up-regulation of VEGF mRNA expression, increase in angiogenesis and prevention of tissue atrophy	[65-67]
Rat	Compression	Human umbilical cord-MSC	Lesion site	Improvement in functional recovery, increase in the intensity of 5-HT fibers and in the volume of spared myelination; decrease in the area of the cystic cavity	[68]
Dog	Compression	Umbilical cord-MSC	Lesion site	Improvement in functional recovery, promotion of neuronal regeneration and reduction of fibrosis	[69]
Dog	Compression	Human umbilical cord-MSC	Lesion site	Improvement in functional recovery and remyelination	[70]
Rat	Contusion	Bone marrow-MSC	Intrathecal	Improvement in functional recovery	[71]
Rat	Contusion	Human bone marrow-MSC	Lesion site , lumbar puncture	Improvement in functional and sensory recovery	[72]
Rat	Contusion	Neural differentiated and undifferentiated MSC	Lesion site	Improvement in functional recovery and reduction of cavitation	[73]

CNS: Central nervous system; MSC: Mesenchymal stem cell; TNF: Tumor necrosis factor; IL: Interleukin; NGF: Nerve growth factor; VEGF: Vascular endothelial growth factor.