PMID- 22472631
OWN - NLM
STAT- MEDLINE
DCOM- 20131223
LR  - 20181203
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 22
IP  - 5
DP  - 2013
TI  - Neural induction with neurogenin 1 enhances the therapeutic potential of 
      mesenchymal stem cells in an amyotrophic lateral sclerosis mouse model.
PG  - 855-70
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by progressive dysfunction 
      and degeneration of motor neurons in the central nervous system (CNS). In the 
      absence of effective drug treatments for ALS, stem cell treatment has emerged as 
      a candidate therapy for this disease. To date, however, there is no consensus 
      protocol that stipulates stem cell types, transplantation timing, or frequency. 
      Using an ALS mouse model carrying a high copy number of a mutant human superoxide 
      dismutase-1 (SOD1)(G93A) transgene, we investigated the effect of neural 
      induction on the innate therapeutic potential of mesenchymal stem cells (MSCs) in 
      relation to preclinical transplantation parameters. In our study, the expression 
      of monocyte chemoattractant protein-1 (MCP-1) was elevated in the ALS mouse 
      spinal cord. Neural induction of MSCs with neurogenin 1 (Ngn1) upregulated the 
      expression level of the MCP-1 receptor, CCR2, and enhanced the migration activity 
      toward MCP-1 in vitro. Ngn1-expressing MSCs (MSCs-Ngn1) showed a corresponding 
      increase in tropism to the CNS after systemic transplantation in ALS mice. 
      Notably, MSCs-Ngn1 delayed disease onset if transplanted during preonset 
      ages,whereas unprocessed MSCs failed to do so. If transplanted near the onset 
      ages, a single treatment with MSCs-Ngn1 was sufficient to enhance motor functions 
      during the symptomatic period (15-17 weeks), whereas unprocessed MSCs required 
      repeated transplantation to achieve similar levels of motor function improvement. 
      Our data indicate that systemically transplanted MSCs-Ngn1 can migrate to the CNS 
      and exert beneficial effects on host neural cells for an extended period of time 
      through paracrine functions, suggesting a potential benefit of neural induction 
      of transplanted MSCs in long-term treatment of ALS.
FAU - Chan-Il, Choi
AU  - Chan-Il C
AD  - Department of Anatomy, Ajou University School of Medicine, Suwon, South Korea.
FAU - Young-Don, Lee
AU  - Young-Don L
FAU - Heejaung, Kim
AU  - Heejaung K
FAU - Kim, Seung Hyun
AU  - Kim SH
FAU - Suh-Kim, Haeyoung
AU  - Suh-Kim H
FAU - Kim, Sung-Soo
AU  - Kim SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, CCR2)
RN  - 0 (SOD1 protein, human)
RN  - 182238-50-2 (Neurog1 protein, mouse)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Amyotrophic Lateral Sclerosis/pathology/*therapy
MH  - Animals
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism
MH  - Bone Marrow Cells/cytology
MH  - Chemokine CCL2/genetics/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Humans
MH  - Male
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Neurons/*metabolism
MH  - Nerve Tissue Proteins/genetics/*metabolism
MH  - Receptors, CCR2/metabolism
MH  - Spinal Cord/metabolism
MH  - Superoxide Dismutase/genetics/metabolism
MH  - Superoxide Dismutase-1
MH  - Transplantation, Heterologous
EDAT- 2012/04/05 06:00
MHDA- 2013/12/24 06:00
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2013/12/24 06:00 [medline]
AID - ct0339choi [pii]
AID - 10.3727/096368912X637019 [doi]
PST - ppublish
SO  - Cell Transplant. 2013;22(5):855-70. doi: 10.3727/096368912X637019.