Regeneration of Autotransplanted Avascular Lymph Nodes in the Rat Is Improved by Platelet-Rich Plasma

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Abstract

The aim of this study was to verify that subcutaneous lymph node transplantation inducing lymphatic regeneration is possible in healthy adult rats, in analogy to results obtained in other species. This rat model was used to determine the effects of lymph node fragmentation as well as sheep erythrocytes and platelet-rich plasma injection on the regeneration of the transplanted lymph nodes. The results show for the first time that the rat is an adequate model to study the regeneration of transplanted lymph nodes. Lymph node fragmentation seems to affect transplant regeneration negatively. An immune challenge by injection of sheep erythrocytes in the drainage area of the transplanted lymph nodes does not improve fragment regeneration. However, injection of syngeneic platelet-rich plasma containing several growth factors resulted in an improvement in regeneration. Lymph node fragment regeneration, although still experimental, could be relevant for lymphedema prevention. Acquired lymphedema has a high prevalence in developed countries as a consequence of the removal and/or radiotherapy of tumor-draining lymph nodes in cancer patients. This disease causes lifelong disability due to chronic swelling and increased risk of infections. It currently lacks an effective treatment.

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Platelet-rich plasma: quantification of growth factor levels and the effect on growth and differentiation of rat bone marrow cells.

P Stoelinga, Juliette Van Steenwinckel, Rob Mooren … (2006)

Platelet-rich plasma (PRP) is a new application of tissue engineering and a developing area for clinicians and researchers. It is a storage vehicle of growth factors (GFs) such as platelet-derived growth factor (PDGF)- AA, -BB, -AB; transforming growth factor (TGF)-beta1 and -2; platelet-derived epidermal growth factor (PDEGF); platelet-derived angiogenesis factor (PDAF); insulin growth factor-1 (IGF-1); and platelet factor- 4 (PF-4), which are known to influence bone regeneration. However, animal and clinical studies reveal different results with the use of PRP and its effect on bone healing. This could be due to the differences between species, that is, differences between species in GF concentrations or variation in presence of GFs between the various PRPs. In this study, rat bone marrow cells were cultured in PRP-coated wells or in uncoated wells for 16 days in osteogenic medium, and analyzed on cell growth (DNA content) and cell differentiation (alkaline phosphatase [ALP] activity, calcium content, scanning electron microscopy, and QPCR). The concentrations of TGF-beta1, PDGF-AA, PDGF-AB, and PDGF-BB in rat, goat, and human PRP were subsequently determined. The results showed that PRP stimulated initial cell growth and had no effect on ALP activity. The calcium measurements showed a significant increase in calcium at days 8, 12, and 16. The real-time PCR results showed that PRP upregulated osteocalcin at day 1 and collagen type I at day 8. Overall, the immunoassays revealed that human PRP contained higher concentrations of growth factors per platelet compared to rat and goat PRP. Goat PRP showed higher concentrations of growth factors per platelet as compared to rat PRP except for PDGF-BB, which had a higher concentration in rat PRP. TGF-beta1 was the most abundant growth factor in all 3 PRPs. On the basis of our results, we conclude that platelet-rich plasma contains osteo-inductive growth factors, which are probably species related. However, we cannot generalize the results because of large intraspecies variations. Further, we conclude that rat PRP gel stimulates initial growth and differentiation of rat bone marrow cells in vitro.

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Molecular mechanisms of lymphatic vascular development.

C Norrmén, T V Petrova, T Mäkinen (2007)

Lymphatic vasculature has recently emerged as a prominent area in biomedical research because of its essential role in the maintenance of normal fluid homeostasis and the involvement in pathogenesis of several human diseases, such as solid tumor metastasis, inflammation and lymphedema. Identification of lymphatic endothelial specific markers and regulators, such as VEGFR-3, VEGF-C/D, PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse models have laid a foundation for our understanding of the major steps controlling growth and remodeling of lymphatic vessels. In this review we summarize recent advances in the field and discuss how this knowledge as well as use of model organisms, such as zebrafish and Xenopus, should allow further in depth analysis of the lymphatic vascular system.

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The microanatomy of T-cell responses.

Tim Lämmermann, Michael Sixt (2008)

The priming of a T cell results from its physical interaction with a dendritic cell (DC) that presents the cognate antigenic peptide. The success rate of such interactions is extremely low, because the precursor frequency of a naive T cell recognizing a specific antigen is in the range of 1:10(5)-10(6). To make this principle practicable, encounter frequencies between DCs and T cells are maximized within lymph nodes (LNs) that are compact immunological projections of the peripheral tissue they drain. But LNs are more than passive meeting places for DCs that immigrated from the tissue and lymphocytes that recirculated via the blood. The microanatomy of the LN stroma actively organizes the cellular encounters by providing preformed migration tracks that create dynamic but highly ordered movement patterns. LN architecture further acts as a sophisticated filtration system that sieves the incoming interstitial fluid at different levels and guarantees that immunologically relevant antigens are loaded on DCs or B cells while inert substances are channeled back into the blood circulation. This review focuses on the non-hematopoietic infrastructure of the lymph node. We describe the association between fibroblastic reticular cell, conduit, DC, and T cell as the essential functional unit of the T-cell cortex.

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Author and article information

Journal

Journal ID (publisher-id): JVR

Journal ID (nlm-ta): J Vasc Res

Journal ID (doi): 10.1159/issn.1018-1172

Title: Journal of Vascular Research

Publisher: S. Karger AG

ISSN (Print): 1018-1172

ISSN (Electronic): 1423-0135

Publication date Subscription-year: 2009

Publication date (Print): August 2009

Publication date (Electronic): 21 January 2009

Volume: 46

Issue: 5

Pages: 389-396

Affiliations

^aInstitute for Functional and Applied Anatomy, and ^bClinic for Diagnostic Radiology, Hannover Medical School, Hannover, Germany

Article

Publisher ID: 194269 Other ID: J Vasc Res 2009;46:389–396

DOI: 10.1159/000194269

PubMed ID: 19155630

SO-VID: 07ff7ddb-030c-4594-93cd-48df363a0b02

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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. 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 government 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.

History

Date received : 07 February 2008

Date accepted : 14 September 2008

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Figures: 6, References: 23, Pages: 8

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Regeneration of Autotransplanted Avascular Lymph Nodes in the Rat Is Improved by Platelet-Rich Plasma

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Abstract

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Karger: Cardiovascular System

Most cited references 17

Platelet-rich plasma: quantification of growth factor levels and the effect on growth and differentiation of rat bone marrow cells.

Molecular mechanisms of lymphatic vascular development.

The microanatomy of T-cell responses.

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Cited by 8

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