Tailless-like (TLX) protein promotes neuronal differentiation of dermal multipotent stem cells and benefits spinal cord injury in rats.
Spinal cord injury (SCI) remains a formidable challenge in the clinic. In the current study, we examined the effects of the TLX gene on the proliferation and neuronal differentiation of dermal multipotent stem cells (DMSCs) in vitro and the potential of these cells to improve SCI in rats in vivo. DMSCs were stably transfected with TLX-expressing plasmid (TLX/DMSCs). Cell proliferation was examined using the MTT assay, and neuronal differentiation was characterized by morphological observation combined with immunocytochemical/immunofluorescent staining. The in vivo functions of these cells were evaluated by transplantation into rats with SCI, followed by analysis of hindlimb locomotion and post-mortem histology. Compared to parental DMSCs, TLX/DMSCs showed enhanced proliferation and preferential differentiation into NF200-positive neurons in contrast to GFAP-positive astrocytes. When the undifferentiated cells were transplanted into rats with SCI injury, TLX/DMSCs led to significant improvement in locomotor recovery and healing of SCI, as evidenced by reduction in scar tissues and cavities, increase in continuous nerve fibers/axons and enrichment of NF200-positive neurons on the histological level. In conclusion, TLX promotes the proliferation and neuronal differentiation of DMSCs and thus, may serve as a promising therapy for SCI in the clinic.
Department of Emergency, Southwest Hospital, The Third Military Medical University of Chinese PLA, Chongqing, China.
Tao
T
Wang
Xiaobao
X
Ren
Jianqiong
J
Xiong
Lei
L
Zhang
Jifu
J
Qu
Wenyue
W
Xu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology*; D006614:Hindlimb / Q000502:physiology; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D020127:Recovery of Function / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology* / Q000534:rehabilitation / Q000601:surgery; D033581:Stem Cell Transplantation
C554080:NR2E1 protein, rat; D018160:Receptors, Cytoplasmic and Nuclear
NeuroRehabilitation. 2003;18(4):339-51
14757930
Nat Cell Biol. 2001 Sep;3(9):778-84
11533656
Nature. 1997 Dec 4;390(6659):515-7
9394001
J Cell Sci. 2010 Mar 15;123(Pt 6):853-60
20159965
J Neurotrauma. 1996 Jul;13(7):343-59
8863191
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2621-5
10706625
Mol Neurobiol. 2008 Dec;38(3):231-41
18931960
Philos Trans R Soc Lond B Biol Sci. 2008 Jan 12;363(1489):185-98
17282990
Cell Transplant. 2007;16(4):355-64
17658126
J Radiat Res. 2004 Mar;45(1):19-24
15133285
Nature. 2004 Jan 1;427(6969):78-83
14702088
J Neurosci Res. 2000 Aug 15;61(4):364-70
10931522
Development. 1998 Jul;125(13):2425-32
9609825
Development. 1995 Mar;121(3):839-53
7720587
Nature. 1993 Aug 12;364(6438):626-32
8394509
Genomics. 1998 May 15;50(1):34-43
9628820
Stem Cells. 2008 Jan;26(1):163-72
17901404
J Neurochem. 2004 Mar;88(6):1335-44
15009633
Cell. 1990 Jul 13;62(1):151-63
2364433
J Neurotrauma. 1995 Feb;12(1):1-21
7783230
AMA Arch Neurol Psychiatry. 1954 Mar;71(3):271-90
13123590
Stem Cells Dev. 2009 Jul-Aug;18(6):893-906
18834279
J Neurotrauma. 2004 Apr;21(4):429-40
15115592
Exp Neurol. 1985 Apr;88(1):123-34
3979506
Exp Neurol. 2003 Oct;183(2):286-97
14552870
Mol Endocrinol. 2008 Jan;22(1):56-64
17901127
Nihon Rinsho. 2003 Mar;61(3):463-8
12701174
Neurosurg Focus. 2008;24(3-4):E19
18341395
Genes Dev. 2010 Apr 1;24(7):683-95
20360385
Stem Cells. 2005 Jun-Jul;23(6):727-37
15917469