A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F19%3A00504807" target="_blank" >RIV/67985904:_____/19:00504807 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/19:00107589
Result on the web
<a href="https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1163-7" target="_blank" >https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1163-7</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1186/s13287-019-1163-7" target="_blank" >10.1186/s13287-019-1163-7</a>
Alternative languages
Result language
angličtina
Original language name
A scalable solution for isolating human multipotent clinical-grade neural stem cells from ES precursors
Original language description
A well-characterized method has not yet been established to reproducibly, efficiently, and safely isolate large numbers of clinical-grade multipotent human neural stem cells (hNSCs) from embryonic stem cells (hESCs). Consequently, the transplantation of neurogenic/gliogenic precursors into the CNS for the purpose of cell replacement or neuroprotection in humans with injury or disease has not achieved widespread testing and implementation.Here, we establish an approach for the in vitro isolation of a highly expandable population of hNSCs using the manual selection of neural precursors based on their colony morphology (CoMo-NSC). The purity and NSC properties of established and extensively expanded CoMo-NSC were validated by expression of NSC markers (flow cytometry, mRNA sequencing), lack of pluripotent markers and by their tumorigenic/differentiation profile after in vivo spinal grafting in three different animal models, including (i) immunodeficient rats, (ii) immunosuppressed ALS rats (SOD1(G93A)), or (iii) spinally injured immunosuppressed minipigs.In vitro analysis of established CoMo-NSCs showed a consistent expression of NSC markers (Sox1, Sox2, Nestin, CD24) with lack of pluripotent markers (Nanog) and stable karyotype for more than 15 passages. Gene profiling and histology revealed that spinally grafted CoMo-NSCs differentiate into neurons, astrocytes, and oligodendrocytes over a 2-6-month period in vivo without forming neoplastic derivatives or abnormal structures. Transplanted CoMo-NSCs formed neurons with synaptic contacts and glia in a variety of host environments including immunodeficient rats, immunosuppressed ALS rats (SOD1G93A), or spinally injured minipigs, indicating these cells have favorable safety and differentiation characteristics.These data demonstrate that manually selected CoMo-NSCs represent a safe and expandable NSC population which can effectively be used in prospective human clinical cell replacement trials for the treatment of a variety of neurodegenerative disorders, including ALS, stroke, spinal traumatic, or spinal ischemic injury.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Stem Cell Research & Therapy
ISSN
1757-6512
e-ISSN
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Volume of the periodical
10
Issue of the periodical within the volume
MAR 12
Country of publishing house
GB - UNITED KINGDOM
Number of pages
19
Pages from-to
83
UT code for WoS article
000461323900008
EID of the result in the Scopus database
2-s2.0-85062873623