Abstract
Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
| Original language | English |
|---|---|
| Pages (from-to) | 723-731 |
| Number of pages | 9 |
| Journal | Nature Methods |
| Volume | 15 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Biotechnology
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Generation and post-injury integration of human spinal cord neural stem cells. / Kumamaru, Hiromi; Kadoya, Ken; Adler, Andrew F.; Takashima, Yoshio; Graham, Lori; Coppola, Giovanni; Tuszynski, Mark H.
In: Nature Methods, Vol. 15, No. 9, 01.09.2018, p. 723-731.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Generation and post-injury integration of human spinal cord neural stem cells
AU - Kumamaru, Hiromi
AU - Kadoya, Ken
AU - Adler, Andrew F.
AU - Takashima, Yoshio
AU - Graham, Lori
AU - Coppola, Giovanni
AU - Tuszynski, Mark H.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
AB - Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for ‘replacement’ strategies in several spinal cord disorders.
UR - http://www.scopus.com/inward/record.url?scp=85052327316&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052327316&partnerID=8YFLogxK
U2 - 10.1038/s41592-018-0074-3
DO - 10.1038/s41592-018-0074-3
M3 - Article
C2 - 30082899
AN - SCOPUS:85052327316
VL - 15
SP - 723
EP - 731
JO - Nature Methods
JF - Nature Methods
SN - 1548-7091
IS - 9
ER -