Table 1 MSC-based preclinical studies in PD treatment

Rats were lesioned by stereotactic injection of 6-OHDA into the right medial forebrain bundle

Stereotaxic method

Because of the dopamine function, CJ-MSCs therapy may protect against PD problems and nerve induction of cells. CJ-MSCs microencapsulation, on the other hand, leads to an even greater protective impact of CJ-MSCs

[65]

30 B57BL/6 mice were lesioned through the intraperitoneal administration of rotenone

Intranasal delivery (IN)

The degeneration caused by rotenone therapy was considerably reversed in mice receiving IN administration of MSCs, demonstrating that IN delivery of MSCs may be a possible safe, straightforward, and cheap alternative method for stem cell treatment in neurodegenerative illnesses

[63]

24 adult female Sprague–Dawley rats were subcutaneously injected with rotenone

Intravenously

The lesioned brains were able to attract BM-MSCs, which resulted in a large drop in serum TGF-1 and monocyte chemoattractant protein-1 (MCP-1) levels, as well as a considerable elevation in serum BDNF and brain DA levels, as well as brain TH and nestin gene expression. Furthermore, treatment with BM-MSCs preserved the histological structure of the striatum in brain slices

[62]

Male Wistar rats lesioned by 6-OHDA intrastriatal injection

Intraarterially

Infusion of rat MSCs had no effect on the progression of 6-OHDA-induced damage or motor impairment during the stepping test, but it did cause progressive normalization of the pathological response (contralateral turning) to apomorphine treatment

[61]

Adult male Wistar rats were lesioned by stereotactic injection of 6-OHDA into the right medial forebrain bundle

Intranigral injection

Subventricular neurogenesis was significantly higher in MSC-transplanted rats compared to non-transplanted animals three days after transplantation. The majority of MSC were discovered in the substantia nigra and adjacent arachnoid mater, expressing S100b and brain-derived neurotrophic factor, whereas some MSC had an endothelial phenotype and were located near blood vessels

[54]

40 adult male Wistar rats received 2 μl 6-OHDA infusions into the medial forebrain bundle

Intranigral infusion

MSC expressing pericyte and endothelial markers were found around the substantia nigra and the arachnoid mater. MSCs increased peripheral antiinflammatory cytokines while preserving dopamine levels. In addition, adipose-derived MSC improved memory performance by increasing neurogenesis in the hippocampus and subventricular areas

[64]

Female Sprague–Dawley rats were lesioned by a single stereotaxic injection of 6-OHDA into the left medial forebrain bundle

Injection into the striatum

In this pilot study, umbilical cord matrix stem (UCMS) cells reduced apomorphine-induced rotations. Brain tumors, rotating behavior, or a frank host immune rejection response were not observed after UCMS cells were transplanted into normal rats

[66]

Rats were lesioned through the unilateral rotenone injection of the ventral tegmental area (VTA) and the SNc

Intrastriatal infusion

HUMSC transplantation reduced apomorphine-evoked rotations and dopaminergic neuron loss in the lesioned SNc, which was greatly aided by VEGF expression in HUMSCs. This paper discusses the feasibility of HUMSC as a vector for gene therapy and argues that stem cell engineering with VEGF may improve the transplantation technique for Parkinson's disease treatment

[67]

Adult female Sprague–Dawley rats were lesioned by unilateral intra-striatal injection of 6-OHDA

Intrastriatal infusion

In a rat model of PD, transplantation of a population of adult bone-marrow MSC induced partially in a neural pathway restores in part the dopaminergic function of the nigrostriatal pathway, leading to an early improvement in behavior, an increased density of dopaminergic markers, and an in vivo recovery of DA release

[15]