PMID- 23826999
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20211021
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 4
IP  - 4
DP  - 2013 Jul 5
TI  - Effective combination of human bone marrow mesenchymal stem cells and minocycline 
      in experimental autoimmune encephalomyelitis mice.
PG  - 77
LID - 10.1186/scrt228 [doi]
AB  - INTRODUCTION: Multiple sclerosis (MS) is the most common inflammatory 
      demyelinating disorder of the central nervous system (CNS). Minocycline 
      ameliorates the clinical severity of MS and exhibits antiinflammatory, 
      neuroprotective activities, and good tolerance for long-term use, whereas it is 
      toxic to the CNS. Recently, the immunomodulation and neuroprotection capabilities 
      of human bone marrow mesenchymal stem cells (hBM-MSCs) were shown in experimental 
      autoimmune encephalomyelitis (EAE). In this study, we evaluated whether the 
      combination of hBM-MSCs and a low-dose minocycline could produce beneficial 
      effects in EAE mice. METHODS: The sensitivity of hBM-MSCs to minocycline was 
      determined by an established cell-viability assay. Minocycline-treated hBM-MSCs 
      were also characterized with flow cytometry by using MSC surface markers and 
      analyzed for their multiple differentiation capacities. EAE was induced in 
      C57BL/6 mice by using immunization with MOG35-55. Immunopathology assays were 
      used to detect the inflammatory cells, demyelination, and neuroprotection. 
      Interferon gamma (IFN-gamma)/tumor necrosis factor alpha (TNF-alpha) and interleukin-4 
      (IL-4)/interleukin-10 (IL-10), the hallmark cytokines that direct Th1 and Th2 
      development, were detected with enzyme-linked immunosorbent assay (ELISA). 
      terminal dUTP nick-end labeling (TUNEL) staining was performed to elucidate the 
      cell apoptosis in the spinal cords of EAE mice. RESULTS: Minocycline did not 
      affect the viability, surface phenotypes, or differentiation capacity of 
      hBM-MSCs, while minocycline affected the viability of astrocytes at a high dose. 
      In vivo efficacy experiments showed that combined treatment, compared to the use 
      of minocycline or hBM-MSCs alone, resulted in a significant reduction in clinical 
      scores, along with attenuation of inflammation, demyelination, and 
      neurodegeneration. Moreover, the combined treatment with hBM-MSCs and minocycline 
      enhanced the immunomodulatory effects, which suppressed proinflammatory cytokines 
      (IFN-gamma, TNF-alpha) and conversely increased anti-inflammatory cytokines (IL-4, 
      IL-10). In addition, TUNEL staining also demonstrated a significant decrease of 
      the number of apoptotic cells in the combined treatment compared with either 
      treatment alone. CONCLUSIONS: The combination of hBM-MSCs and minocycline 
      provides a novel experimental protocol to enhance the therapeutic effects in MS.
FAU - Hou, Yun
AU  - Hou Y
FAU - Ryu, Chung Heon
AU  - Ryu CH
FAU - Park, Kwang Ywel
AU  - Park KY
FAU - Kim, Seong Muk
AU  - Kim SM
FAU - Jeong, Chang Hyun
AU  - Jeong CH
FAU - Jeun, Sin-Soo
AU  - Jeun SS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130705
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - 0 (Anti-Bacterial Agents)
RN  - FYY3R43WGO (Minocycline)
SB  - IM
MH  - Animals
MH  - Anti-Bacterial Agents/*therapeutic use
MH  - Apoptosis
MH  - Bone Marrow Cells/*metabolism
MH  - Cell Differentiation
MH  - Disease Models, Animal
MH  - Encephalomyelitis, Autoimmune, Experimental/genetics/*metabolism
MH  - Humans
MH  - Mesenchymal Stem Cell Transplantation/*methods
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Minocycline/*therapeutic use
PMC - PMC3854709
EDAT- 2013/07/06 06:00
MHDA- 2015/05/12 06:00
PMCR- 2013/07/05
CRDT- 2013/07/06 06:00
PHST- 2012/12/07 00:00 [received]
PHST- 2013/07/01 00:00 [accepted]
PHST- 2013/07/06 06:00 [entrez]
PHST- 2013/07/06 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
PHST- 2013/07/05 00:00 [pmc-release]
AID - scrt228 [pii]
AID - 10.1186/scrt228 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2013 Jul 5;4(4):77. doi: 10.1186/scrt228.