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Vol. 27, No. 5, 2011
Issue release date: 2011
Section title: Original Paper
Cell Physiol Biochem 2011;27:587–596
(DOI:10.1159/000329980)

Intrapulmonary Delivery of Human Umbilical Cord Mesenchymal Stem Cells Attenuates Acute Lung Injury by Expanding CD4+CD25+ Forkhead Boxp3 (FOXP3) + Regulatory T Cells and Balancing Anti- and Pro-inflammatory Factors

Sun J.1 · Han Z.-B.1,2 · Liao W.1 · Yang S.G.1 · Yang Z.X.1 · Yu J.X.1 · Meng L.1 · Wu R.3 · Han Z.C.1,2
1The State key Laboratory of Experimental Hematology, National Engineering Technology Research Center of Stem Cells, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union of Medical College Tsinghua university, Tianjin;2National Engineering Research Center of Cell Products, AmCellGene Co. Ltd, Tianjin;3Department of Pediatrics, the Hospital of HuaiAn, Jiangsu Province, China
email Corresponding Author

Abstract

Background: Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4+CD25+ Foxp3+Treg cells and lead to an improvement in ALI. Methods: Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) and received intrapulmonary 1×106 UCMSC 4 hours after challenge. The CD4+CD25+ Foxp3+Treg, survival time, body weight, histology and lung injury scores were assessed after transplantation of UCMSC. In addition, anti-inflammatory factor IL10 and pro-inflammatory mediators production including tumor necrosis factor-a (TNF-α), macrophage inflammatory protein-2(MIP-2) and interferon-γ (IFN-γ) were detected. Results: Transplantation of UCMSC resulted in significant increase in the level of CD4+CD25+ Foxp3+Treg in ALI. Increased level of anti-inflammatory factor IL-10 and reduced levels of TNF-α, MIP-2 and IFN-γ were simultaneously observed in ALI in comparison with control mice. Conclusion: Our data demonstrate for the first time that transplantation of UCMSC ameliorates ALI by enhancing the diminished levels of alveolar CD4+CD25+ Foxp3+Treg and balancing anti- and pro-inflammatory factors in ALI mice.

© 2011 S. Karger AG, Basel


  

Key Words

  • UC-MSC
  • CD4+CD25+ Foxp3+Treg
  • Acute lung injury
  • LPS

  

Author Contacts

Prof. Zhong Chao Han
The State key Laboratory of Experimental Hematology, Institute of Hematology
and Hospital of Blood Diseases, 288 Nanjing Road, Tianjin 300020 (China)
Tel. +86 22 66211430, Fax +86 22 66211430; E-Mail hanzhongchao@hotmail.com
or E-Mail sunjun2008387@gmail.com (Jun Sun)

  

Article Information

Accepted: April 27, 2011
Published online: June 15, 2011
Number of Print Pages : 10

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 27, No. 5, Year 2011 (Cover Date: 2011)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Systemic and local inflammatory processes play key, mainly detrimental roles in the pathophysiology of acute lung injury (ALI). The present study was designed to determine whether human umbilical cord mesenchymal stem cells (UCMSC) are able to act on CD4+CD25+ Foxp3+Treg cells and lead to an improvement in ALI. Methods: Mice were administered intratracheally endotoxin (lipopolysaccharide [LPS]) and received intrapulmonary 1×106 UCMSC 4 hours after challenge. The CD4+CD25+ Foxp3+Treg, survival time, body weight, histology and lung injury scores were assessed after transplantation of UCMSC. In addition, anti-inflammatory factor IL10 and pro-inflammatory mediators production including tumor necrosis factor-a (TNF-α), macrophage inflammatory protein-2(MIP-2) and interferon-γ (IFN-γ) were detected. Results: Transplantation of UCMSC resulted in significant increase in the level of CD4+CD25+ Foxp3+Treg in ALI. Increased level of anti-inflammatory factor IL-10 and reduced levels of TNF-α, MIP-2 and IFN-γ were simultaneously observed in ALI in comparison with control mice. Conclusion: Our data demonstrate for the first time that transplantation of UCMSC ameliorates ALI by enhancing the diminished levels of alveolar CD4+CD25+ Foxp3+Treg and balancing anti- and pro-inflammatory factors in ALI mice.

© 2011 S. Karger AG, Basel


  

Author Contacts

Prof. Zhong Chao Han
The State key Laboratory of Experimental Hematology, Institute of Hematology
and Hospital of Blood Diseases, 288 Nanjing Road, Tianjin 300020 (China)
Tel. +86 22 66211430, Fax +86 22 66211430; E-Mail hanzhongchao@hotmail.com
or E-Mail sunjun2008387@gmail.com (Jun Sun)

  

Article Information

Accepted: April 27, 2011
Published online: June 15, 2011
Number of Print Pages : 10

  

Publication Details

Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)

Vol. 27, No. 5, Year 2011 (Cover Date: 2011)

Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)

For additional information: http://www.karger.com/journals/cpb


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: 4/27/2011
Published online: 6/15/2011
Issue release date: 2011

Number of Print Pages: 0
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: http://www.karger.com/CPB


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.