Neurons derived from human mesenchymal stem cells show synaptic transmission and can be induced to produce the neurotransmitter substance P by interleukin-1 alpha.
Mesenchymal stem cells (MSCs) exhibit immune-suppressive properties, follow a pattern of multilineage differentiation, and exhibit transdifferentiation potential. Ease in expansion from adult bone marrow, as well as its separation from ethical issues, makes MSCs appealing for clinical application. MSCs treated with retinoic acid resulted in synaptic transmission, based on immunostaining of synaptophysin and electrophysiological studies. In situ hybridization indicated that the neurotransmitter gene preprotachykinin-I was expressed in these cells. However, translation of this gene only occurred after stimulation with interleukin (IL)-1 alpha. This effect was blunted by costimulation with IL-1 receptor antagonist. This study reports on the ability of MSCs to be transdifferentiated into neurons with functional synapses with the potential to become polarized towards producing specific neurotransmitters.
Cho
Kyung Jin
KJ
Department of Medicine, Hematology/Oncology, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA.
Trzaska
Katarzyna A
KA
Greco
Steven J
SJ
McArdle
Joseph
J
Wang
Fu Shun
FS
Ye
Jiang-Hong
JH
Rameshwar
Pranela
P
D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D004594:Electrophysiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics; D012795:Sialoglycoproteins / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D007381:Intermediate Filament Proteins; C489788:MAP2 protein, human; D008869:Microtubule-Associated Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; D064231:Nestin; D016900:Neurofilament Proteins; D011498:Protein Precursors; D012795:Sialoglycoproteins; D016708:Synaptophysin; D015320:Tachykinins; C044206:preprotachykinin; D013373:Substance P; D014212:Tretinoin