PMID- 23452894
OWN - NLM
STAT- MEDLINE
DCOM- 20141215
LR  - 20220822
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 23
IP  - 6
DP  - 2014 Apr
TI  - Combination cell therapy using mesenchymal stem cells and regulatory T-cells 
      provides a synergistic immunomodulatory effect associated with reciprocal 
      regulation of TH1/TH2 and th17/treg cells in a murine acute graft-versus-host 
      disease model.
PG  - 703-14
LID - 10.3727/096368913X664577 [doi]
AB  - Mesenchymal stem cells (MSCs) have been considered to be an ideal cellular source 
      for graft-versus-host disease (GVHD) treatment due to their unique properties, 
      including tissue repair and major histocompatibility complex (MHC)-unmatched 
      immunosuppression. However, preclinical and clinical data have suggested that the 
      immunomodulatory activity of MSCs is not as effective as previously expected. 
      This study was performed to investigate whether the immunomodulatory capacity of 
      MSCs could be enhanced by combination infusion of regulatory T (Treg) cells to 
      prevent acute GVHD (aGVHD) following MHC-mismatched bone marrow transplantation 
      (BMT). For GVHD induction, lethally irradiated BALB/c (H-2(d)) mice were 
      transplanted with bone marrow cells (BMCs) and spleen cells of C57BL/6 (H-2(b)) 
      mice. Recipients were injected with cultured recipient-derived MSCs, Treg cells, 
      or MSCs plus Treg cells (BMT + day 0, 4). Systemic infusion of MSCs plus Treg 
      cells improved clinicopathological manifestations and survival in the aGVHD 
      model. Culture of MSCs plus Treg cells increased the population of Foxp3(+) Treg 
      cells and suppressed alloreactive T-cell proliferation in vitro. These 
      therapeutic effects were associated with more rapid expansion of donor-type 
      CD4(+)CD25(+)Foxp3(+) Treg cells and CD4(+)IL-4(+) type 2 T-helper (Th2) cells in 
      the early posttransplant period. Furthermore, MSCs plus Treg cells regulated 
      CD4(+)IL-17(+) Th17 cells, as well as CD4(+)IFN-gamma(+) Th1 cells. These data 
      suggest that the combination therapy with MSCs plus Treg cells may have 
      cooperative effects in enhancing the immunomodulatory activity of MSCs and Treg 
      cells in aGVHD. This may lead to development of new therapeutic approaches to 
      clinical allogeneic hematopoietic cell transplantation.
FAU - Lim, Jung-Yeon
AU  - Lim JY
AD  - Laboratory of Immune Regulation, Convergent Research Consortium for Immunologic 
      Disease, Seoul St. Mary's Hospital, The Catholic University of Korea College of 
      Medicine, Seoul, Korea.
FAU - Park, Min-Jung
AU  - Park MJ
FAU - Im, Keon-Il
AU  - Im KI
FAU - Kim, Nayoun
AU  - Kim N
FAU - Jeon, Eun-Joo
AU  - Jeon EJ
FAU - Kim, Eun-Jung
AU  - Kim EJ
FAU - Cho, Mi-La
AU  - Cho ML
FAU - Cho, Seok-Goo
AU  - Cho SG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130226
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (FOXP3 protein, human)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell- and Tissue-Based Therapy
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Female
MH  - Forkhead Transcription Factors/metabolism
MH  - Graft vs Host Disease/immunology/pathology/*prevention & control
MH  - *Immunomodulation
MH  - Interleukin-10/analysis/metabolism
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Phenotype
MH  - Spleen/cytology
MH  - T-Lymphocytes, Regulatory/cytology/*transplantation
MH  - Transforming Growth Factor beta/analysis/metabolism
EDAT- 2013/03/05 06:00
MHDA- 2014/12/17 06:00
CRDT- 2013/03/05 06:00
PHST- 2013/03/05 06:00 [entrez]
PHST- 2013/03/05 06:00 [pubmed]
PHST- 2014/12/17 06:00 [medline]
AID - ct0956lim [pii]
AID - 10.3727/096368913X664577 [doi]
PST - ppublish
SO  - Cell Transplant. 2014 Apr;23(6):703-14. doi: 10.3727/096368913X664577. Epub 2013 
      Feb 26.