Back to Browse Journals » International Journal of Nanomedicine » Volume 7

Skin regeneration with conical and hair follicle structure of deep second-degree scalding injuries via combined expression of the EPO receptor and beta common receptor by local subcutaneous injection of nanosized rhEPO

Authors Bader A, Ebert S, Giri S, Kremer M, Liu S, Nerlich A, Günter CI, Smith DU, Machens HG

Published Date March 2012 Volume 2012:7 Pages 1227—1237

DOI http://dx.doi.org/10.2147/IJN.S28186

Received 12 November 2011, Accepted 6 December 2011, Published 6 March 2012

Augustinus Bader1, Sabine Ebert1, Shibashish Giri1, Mathias Kremer2, Shuhua Liu2, Andreas Nerlich5, Christina I Günter³, Dagmar U Smith4, Hans-Günther Machens2,3
1Department of Applied Stem Cell Biology and Cell Techniques, Centre for Biotechnology and Biomedicine, University of Leipzig, Leipzieg, 2Department of Plastic and Hand Surgery, University of Lübeck, Lübeck, 3Department of Plastic and Hand Surgery, Technische Universität München, Munich, 4Münchner Studienzentrum, Technische Universität München, Munich, 5Institute of Pathology, Klinikum München-Bogenhausen, Munich, Germany

Background: Acceleration of skin regeneration is still an unsolved problem in the clinical treatment of patients suffering from deep burns and scalds. Although erythropoietin (EPO) has a protective role in a wide range of organs and cells during ischemia and after trauma, it has been recently discovered that EPO is not tissue-protective in the common β subunit receptor (βCR) knockout mouse. The protective capacity of EPO in tissue is mediated via a heteroreceptor complex comprising both the erythropoietin receptor (EPOR) and βCR. However, proof of coexpression of these heterogenic receptors in regenerating skin after burns is still lacking.
Methods: To understand the role of nanosized recombinant human erythropoietin (rhEPO) in wound healing, we investigated the effects of subcutaneous injections of EPO on skin regeneration after deep second-degree scalding injuries. Our aim was to determine if joint expression of EPOR and βCR is a prerequisite for the tissue-protective effect of rhEPO. The efficiency in wound regeneration in a skin scalding injury mouse model was examined. A deep second-degree dermal scald injury was produced on the backs of 20 female Balb/c mice which were subsequently randomized to four experimental groups, two of which received daily subcutaneous injections of rhEPO. At days 7 and 14, the mice were sacrificed and the effects of rhEPO were analyzed with respect to grade of re-epithelialization (wound closure) and stage of epidermal maturation. This was investigated using different histological parameters of epithelial covering, such as depth of the epidermal layer, epidermal stratification, and presence of conical and hair follicle structures.
Results: Expression of EPOR, βCR, and growth hormone receptor at the mRNA and protein levels was demonstrated with reverse transcriptase polymerase chain reaction and Western blot analysis. After rhEPO treatment, the rate of re-epithelialization of the scalding injury was increased and the time to final wound closure was reduced. In addition, the quality of regenerated skin was improved. In this investigation, for the first time, we demonstrated coexpression of EPOR and βCR at the RNA and protein levels in vivo using a deep second-degree scalding injury mouse model. These results highlight the potential role of rhEPO in the improved treatment of burns patients, which might be crucial for the development of innovative new therapy regimes.
Conclusion: Local injection of nanosized rhEPO directly to the injury site rather than systemic administration for deep second-degree scalding injuries achieved complete skin regeneration with conical and hair follicle structure via combined expression of EPOR and βCR.

Keywords: burns, nanosize, common β subunit, erythropoietin, receptor, local injection

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Other article by this author:

Skin regeneration in deep second-degree scald injuries either by infusion pumping or topical application of recombinant human erythropoietin gel

Giri P, Ebert S, Braumann UD, Kremer M, Giri S, Machens HG, Bader A

Drug Design, Development and Therapy 2015, 9:2565-2579

Published Date: 11 May 2015

Readers of this article also read:

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

Sun S, Liang N, Yamamoto H, Kawashima Y, Cui F, Yan P

International Journal of Nanomedicine 2015, 10:3489-3498

Published Date: 11 May 2015

Development of an oral push–pull osmotic pump of fenofibrate-loaded mesoporous silica nanoparticles

Zhao Z, Wu C, Zhao Y, Hao Y, Liu Y, Zhao W

International Journal of Nanomedicine 2015, 10:1691-1701

Published Date: 3 March 2015

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies

Wang Z, Mu HJ, Zhang XM, Ma PK, Lian SN, Zhang FP, Chu SY, Zhang WW, Wang AP, Wang WY, Sun KX

International Journal of Nanomedicine 2015, 10:633-644

Published Date: 14 January 2015

Photothermal cancer therapy using graphitic carbon–coated magnetic particles prepared by one-pot synthesis

Lee HJ, Sanetuntikul J, Choi ES, Lee BR, Kim JH, Kim E, Shanmugam S

International Journal of Nanomedicine 2015, 10:271-282

Published Date: 30 December 2014

Interleukin 10-coated nanoparticle systems compared for molecular imaging of atherosclerotic lesions

Almer G, Summers KL, Scheicher B, Kellner J, Stelzer I, Leitinger G, Gries A, Prassl R, Zimmer A, Mangge H

International Journal of Nanomedicine 2014, 9:4211-4222

Published Date: 3 September 2014

Targeting nanomaterials: future drugs for cancer chemotherapy

Zhang Y, Chen T

International Journal of Nanomedicine 2012, 7:5283-5286

Published Date: 10 October 2012

Retraction

Cárdenas WH, Mamani JB, Sibov TT, Caous CA, Amaro E Jr, Gamarra LF

International Journal of Nanomedicine 2012, 7:5107-5108

Published Date: 21 September 2012

Biofunctionalization of a titanium surface with a nano-sawtooth structure regulates the behavior of rat bone marrow mesenchymal stem cells

Zhang WJ, Li ZH, Liu Y, Ye DX, Li JH, Xu LY, Wei B, Zhang XL, Liu XY, Jiang XQ

International Journal of Nanomedicine 2012, 7:4459-4472

Published Date: 13 August 2012

Corrigendum

Chen ZQ, Liu Y, Zhao JH, Wang L, Feng NP

International Journal of Nanomedicine 2012, 7:1709-1710

Published Date: 30 March 2012