Abstract
Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron–Schwann cell (MN–SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs. Following coculture with SCs on the microfluidic biochip, MNs were transfected with a light-sensitive channelrhodopsin gene. Transfected MNs subjected to repeated light stimulation (20 Hz, 1 hr) produced significantly longer axons than nontransfected MNs. OMLS of MNs greatly increased the number of myelin basic protein (MBP)-expressing SCs, promoting the initiation of myelination of MNs. Ultrastructurally, OMLS of MNs markedly enhanced the thickness of the compact myelin sheath around the MN axons such that the average thickness was closer to that of the theoretical estimates in vivo. Thus, the MN–SC coculture model on a microfluidic biochip augmented by OMLS of MNs is a feasible platform for studying the relationship of neuronal activity with regrowth and remyelination.
| Original language | English |
|---|---|
| Pages (from-to) | 2425-2438 |
| Number of pages | 14 |
| Journal | Biotechnology and Bioengineering |
| Volume | 116 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2019 Oct 1 |
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All Science Journal Classification (ASJC) codes
- Biotechnology
- Bioengineering
- Applied Microbiology and Biotechnology
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Optogenetic neuronal stimulation promotes axon outgrowth and myelination of motor neurons in a three-dimensional motor neuron–Schwann cell coculture model on a microfluidic biochip. / Hyung, Sujin; Lee, Seung Ryeol; Kim, Yeon Jee; Bang, Seokyoung; Tahk, Dongha; Park, Jong Chul; Suh, Jun Kyo Francis; Jeon, Noo Li.
In: Biotechnology and Bioengineering, Vol. 116, No. 10, 01.10.2019, p. 2425-2438.Research output: Contribution to journal › Article
TY - JOUR
T1 - Optogenetic neuronal stimulation promotes axon outgrowth and myelination of motor neurons in a three-dimensional motor neuron–Schwann cell coculture model on a microfluidic biochip
AU - Hyung, Sujin
AU - Lee, Seung Ryeol
AU - Kim, Yeon Jee
AU - Bang, Seokyoung
AU - Tahk, Dongha
AU - Park, Jong Chul
AU - Suh, Jun Kyo Francis
AU - Jeon, Noo Li
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron–Schwann cell (MN–SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs. Following coculture with SCs on the microfluidic biochip, MNs were transfected with a light-sensitive channelrhodopsin gene. Transfected MNs subjected to repeated light stimulation (20 Hz, 1 hr) produced significantly longer axons than nontransfected MNs. OMLS of MNs greatly increased the number of myelin basic protein (MBP)-expressing SCs, promoting the initiation of myelination of MNs. Ultrastructurally, OMLS of MNs markedly enhanced the thickness of the compact myelin sheath around the MN axons such that the average thickness was closer to that of the theoretical estimates in vivo. Thus, the MN–SC coculture model on a microfluidic biochip augmented by OMLS of MNs is a feasible platform for studying the relationship of neuronal activity with regrowth and remyelination.
AB - Axonal regeneration and remyelination of peripheral motor neurons (MNs) are critical for restoring neuromuscular motor function after injury or peripheral neuropathy. We examined whether optogenetically mediated light stimulation (OMLS) could enhance the axon outgrowth and myelination of MNs using three-dimensional motor neuron–Schwann cell (MN–SC) coculture on a microfluidic biochip. The biochip was designed to allow SCs to interact with the axons of MNs, while preventing direct contact between SCs and the cell bodies of MNs. Following coculture with SCs on the microfluidic biochip, MNs were transfected with a light-sensitive channelrhodopsin gene. Transfected MNs subjected to repeated light stimulation (20 Hz, 1 hr) produced significantly longer axons than nontransfected MNs. OMLS of MNs greatly increased the number of myelin basic protein (MBP)-expressing SCs, promoting the initiation of myelination of MNs. Ultrastructurally, OMLS of MNs markedly enhanced the thickness of the compact myelin sheath around the MN axons such that the average thickness was closer to that of the theoretical estimates in vivo. Thus, the MN–SC coculture model on a microfluidic biochip augmented by OMLS of MNs is a feasible platform for studying the relationship of neuronal activity with regrowth and remyelination.
UR - http://www.scopus.com/inward/record.url?scp=85068518803&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068518803&partnerID=8YFLogxK
U2 - 10.1002/bit.27083
DO - 10.1002/bit.27083
M3 - Article
C2 - 31180148
AN - SCOPUS:85068518803
VL - 116
SP - 2425
EP - 2438
JO - Biotechnology and Bioengineering
JF - Biotechnology and Bioengineering
SN - 0006-3592
IS - 10
ER -