TY - JOUR
T1 - mRNA-Driven generation of transgene-free neural stem cells from human urine-derived cells
AU - Kang, Phil Jun
AU - Son, Daryeon
AU - Ko, Tae Hee
AU - Hong, Wonjun
AU - Yun, Wonjin
AU - Jang, Jihoon
AU - Choi, Jong Il
AU - Song, Gwonhwa
AU - Lee, Jangbo
AU - Kim, In Yong
AU - You, Seungkwon
N1 - Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/9
Y1 - 2019/9
N2 - Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, effcient, and patient-specific manner.
AB - Human neural stem cells (NSCs) hold enormous promise for neurological disorders, typically requiring their expandable and differentiable properties for regeneration of damaged neural tissues. Despite the therapeutic potential of induced NSCs (iNSCs), a major challenge for clinical feasibility is the presence of integrated transgenes in the host genome, contributing to the risk for undesired genotoxicity and tumorigenesis. Here, we describe the advanced transgene-free generation of iNSCs from human urine-derived cells (HUCs) by combining a cocktail of defined small molecules with self-replicable mRNA delivery. The established iNSCs were completely transgene-free in their cytosol and genome and further resembled human embryonic stem cell-derived NSCs in the morphology, biological characteristics, global gene expression, and potential to differentiate into functional neurons, astrocytes, and oligodendrocytes. Moreover, iNSC colonies were observed within eight days under optimized conditions, and no teratomas formed in vivo, implying the absence of pluripotent cells. This study proposes an approach to generate transplantable iNSCs that can be broadly applied for neurological disorders in a safe, effcient, and patient-specific manner.
KW - Direct conversion
KW - Induced neural stemcells (iNSCs)
KW - Neurological diseases
KW - Reprogramming
KW - Self-replicativemRNA
KW - Small molecules
UR - http://www.scopus.com/inward/record.url?scp=85085232929&partnerID=8YFLogxK
U2 - 10.3390/cells8091043
DO - 10.3390/cells8091043
M3 - Article
C2 - 31489945
AN - SCOPUS:85085232929
SN - 2073-4409
VL - 8
JO - Cells
JF - Cells
IS - 9
M1 - 1043
ER -