=====Induced neural stem cell=====
[[Reprogramming]] adult human [[fibroblast]]s to iNSC by [[plasmid]] [[vector]]s and basic [[neural medium]] without small molecules is possible and feasible. However, a full set of pluripotency-associated [[transcription factor]]s may indeed result in the acquisition of a transient (at least partial) pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside the cells at all time points
((Capetian P, Azmitia L, Pauly MG, Krajka V, Stengel F, Bernhardi EM, Klett M,
Meier B, Seibler P, Stanslowsky N, Moser A, Knopp A, Gillessen-Kaesbach G,
Nikkhah G, Wegner F, Döbrössy M, Klein C. Plasmid-Based Generation of Induced
Neural Stem Cells from Adult Human Fibroblasts. Front Cell Neurosci. 2016 Oct
24;10:245. eCollection 2016. PubMed PMID: 27822179; PubMed Central PMCID:
PMC5075569.
)).

[[Transdifferentiation]] can be used to create induced [[neural stem cell]]s (iNSCs). Previous in vivo research using induced [[pluripotent stem cell]]s has been stymied by the formation of cancerous teratomas. However, iNSCs have not shown such in vivo teratoma formation, suggesting that iNSCs can provide safe, patient-specific cell transplantation therapy to treat disorders of the central nervous system
((Bagó JR, Alfonso-Pecchio A, Okolie O, et al. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nat Commun. 2016;7:10593.))
((Uzzaman M, Benveniste RJ, Keller G, Germano IM. Embryonic stem cell–derived astrocytes: a novel gene therapy vector for brain tumors. Neurosurg Focus. 2005;19(3):1–6.)).

NSCs exhibit tumoritropic migration, allowing unprecedented access to [[glioblastoma]] GBM [[cancer cell]]s. NSCs also have the ability to release anticancer molecules that could provide long-term drug delivery directly to the cancer cells
((Uzzaman M, Benveniste RJ, Keller G, Germano IM. Embryonic stem cell–derived astrocytes: a novel gene therapy vector for brain tumors. Neurosurg Focus. 2005;19(3):1–6.)).

However, NSCs are located deep within the adult brain and are not readily available without invasive surgery. A recent study by Bagó et al
((Bagó JR, Alfonso-Pecchio A, Okolie O, et al. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nat Commun. 2016;7:10593.))
shows a potential means of inducing NSCs from skin fibroblasts and specifically delivering tumoricidal treatments to GBM in vivo.

The use of iNSCs could potentially lead to highly selective delivery of therapeutics to brain tumors, reducing systemic toxicities and improving efficacy. Many clinical trials are currently underway that are using TRAIL-based treatments in a variety of cancers, including leukemia, lymphoma, colorectal cancer, and GBM
((Chakraborty S, Bodhinayake I, Chiluwal A, et al. Neuro-oncology biotech industry progress report. J Neurooncol. 2016;128(1):175–182.)).
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Induced [[neural stem cell]]s (iNSCs), similar to neural stem cells (NSCs), can accelerate neurological recovery in vivo and produce [[neurotrophic factor]]s in vitro.

Whether iNSCs have immunomodulatory properties is unknown. 

Mouse models of [[closed head injury]] (CHI) were established using a standardized weight-drop device and assessed by neurological severity score (NSS). Although these models fail to mimic the complete spectrum of human CHI, they reproduce impairment in neurological function observed in clinical patients. Syngeneic iNSCs or NSCs were separately transplanted into the brains of CHI mice at 12h after CHI. Neurological impairment post-CHI was evaluated by several tests. Animals were sacrificed for morphological and molecular biological analyses. 

Gao et al. discovered that iNSC administration promoted neurological functional recovery in CHI mice and reduced [[cerebral edema]], BBB disruption, [[cell death]] and astroglial scarring following trauma. Implanted iNSCs could up-regulate [[brain derived neurotrophic factor]] (BDNF) and [[glial derived neurotrophic factor]] (GDNF) levels to support the survival of existing neurons after CHI. In addition, engrafted iNSCs decreased immune cell recruitment and pro-inflammatory cytokine expression in the brain post-injury. Moreover, we found significant [[nuclear factor kappa]]B (NF-κB) inhibition in the presence of iNSC grafts. In short, iNSCs exert neurotrophic and immunomodulatory effects that mitigate CHI-induced neurological impairment
((Gao M, Yao H, Dong Q, Zhang Y, Yang Y, Zhang Y, Yang Z, Xu M, Xu R.
Neurotrophy and immunomodulation of induced neural stem cell grafts in a mouse
model of closed head injury. Stem Cell Res. 2017 Jul 18;23:132-142. doi:
10.1016/j.scr.2017.07.015. [Epub ahead of print] PubMed PMID: 28743043.)).