Therapeutic Potential of Induced Neural Stem Cells for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a chronic, neurodegenerative disorder that results from the loss of cells in the substantia nigra (SN) which is located in the midbrain. However, no cure is available for PD. Recently, fibroblasts have been directly converted into induced neural stem cells (iNSCs) via the forced expression of specific transcription factors. Therapeutic potential of iNSC in PD has not been investigated yet. Here, we show that iNSCs directly converted from mouse fibroblasts enhanced functional recovery in an animal model of PD. The rotational behavior test was performed to assess recovery. Our results indicate that iNSC transplantation into the striatum of 6-hydroxydopamine (6-OHDA)-injected mice can significantly reduce apomorphine-induced rotational asymmetry. The engrafted iNSCs were able to survive in the striatum and migrated around the medial forebrain bundle and the SN pars compacta. Moreover, iNSCs differentiated into all neuronal lineages. In particular, the transplanted iNSCs that committed to the glial lineage were significantly increased in the striatum of 6-OHDA-injected mice. Engrafted iNSCs differentiated to dopaminergic (DA) neurons and migrated into the SN in the 6-OHDA lesion mice. Therefore, iNSC transplantation serves as a valuable tool to enhance the functional recovery in PD.

Take the shortcut – direct conversion of somatic cells into induced neural stem cells and their biomedical applications

“…The iNSC-derived cells migrated and differentiated and, most importantly, restore damaged tissues reconstituting the local circuitry. Restoration of brain tissue led to an enhanced functional recovery of the animals in behavioral assessment [77]. Ten weeks after transplantation, rats showed partial reconstitution of their locomotor function [88].…”

“…Other iNSC populations gave only rise to neurons and astrocytes [11,26,35,78]. Regarding neuronal subtypes, iNSCs were shown to have the potential to differentiate into the main neuronal subtypes, including glutamatergic [28,30,32,36,48,57,59,60,73,77], GABAergic [11,13,28,30,32,36,38,48,57,59,60,77], dopaminergic [14,25,28,30,33,34,36,48,57,73], serotonergic [25,28], and cholinergic neurons [14,25,28,34,36,48,60,73]. Regarding neuronal subtypes, iNSCs were shown to have the potential to differentiate into the main neuronal subtypes, including glutamatergic [28,30,…”

“…In comparison with iPSCs, iNSCs represent a more feasible and cost-efficient source of NSCs for clinical applications [77]. Several transplantation studies in animal models of human pathologies, including acute and chronic brain damage and brain cancer, have explored the therapeutic potential of iNSCs.…”

Stem Cells Engineered During Different Stages of Reprogramming Reveal Varying Therapeutic Efficacies

“…GBM tumor resections were performed as described previously . Specifically, cranial windows were created in SCID mice ( n = 32) and primary patient derived GBM, GBM18‐FmC were stereotactically implanted in mice.…”

“…Fluorescence guided tumor debulking was performed on mice ( n = 24) 10 days post tumor implantation. In order to study the therapeutic effect of ipNSC‐TRTK, ipNSC cells were encapsulated in synthetic‐extracellular‐matrix (sECM) as described previously . sECM encapsulated ipNSC‐TRTK were then placed in the tumor resection cavity and mice for followed for changes in tumor volumes by BLI.…”