Lymphedema is not a sexy topic so there hasn't been a lot of money put into lympedema research, unfortunately
Compression sleeves and manal draining seem to be the first steps listed in the literature, but there are not a lot of large studies and lymphedema has in the past been difficult to accurately measure, making meaningful comparisons of alternate treatments difficult
NEVERTHELESS DURING THE PAST WEEK THERE WERE 2 HOPEFUL ARTICLES PUBLISHED--hot off the press, but not yet ready for prime time FOR TREATMENT THOUGHT YOU MIGHT FIND THEM INTERESTING AS THEY SHOW AT LEAST SOMEONE IS LOOKING INTO THE AREA
: Public release date: 26-Aug-2013
http://www.eurekalert.org/pub_releas...-nff082613.php
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Contact: Cornelia Halin
cornelia.halin@pharma.ethz.ch
41-446-332-962
ETH Zurich
New function for a well-known immune messenger molecule
The molecule interleukin-7 (IL-7) is an important immune messenger protein which ensures that a
sufficient number of T cells are present in our body for immune defence. Researchers from ETH Zurich
have now demonstrated that IL-7 has another important function: it enhances the drainage function
of lymphatic vessels, which collect fluid that has leaked out of blood vessels into the body tissue and
return it to the bloodstream. In the future, this finding could become useful for lymphedema patients,
whose lymphatic drainage system does not work properly, resulting in fluid accumulation and tissue
swelling.
The predisposition to develop lymphedema may, on one hand, be hereditary. On the other hand,
lymphedema often occurs in the aftermath of a tumour surgery. When primary tumours are surgically
excised, tumour-draining lymph nodes are often removed as well, as they may contain tumour cell
metastases. In the course of such surgical interventions, the lymphatic tissue is damaged. As a
result, tissue fluid can often no longer be drained properly, leading to the occurrence of lymphedema
in 20 to 30 per cent of patients.
No drug treatment yet
Currently, the only treatment options for lymphedema patients are wearing compression garments
and undergoing manual lymph drainage by a medical massage therapist. "In IL-7, we have
discovered a molecule and a mechanism for enhancing lymphatic drainage which could potentially be
useful for lymphedema therapy," says the head of the study Cornelia Halin, Assistant Professor of
Drug Discovery Technologies.
In their study, the researchers found that IL-7 is produced by the so-called endothelial cells, which
form the lymphatic vessel wall. These cells also express the receptors that specifically recognise IL-7
based on the lock-and-key principle. "Although we have not formally proven it so far, we assume that
the lymphatic endothelial cells produce the messenger substance so that it can affect their own
function directly," says Halin. So far, IL-7 is one out of only few molecules that have been identified
to support lymphatic drainage. A few years ago, other researchers discovered that the endogenous
growth factor VEGF-C might also be an interesting molecule in this regard.
Insights from an animal model
Halin and her colleagues demonstrated the drainage-supporting function of IL-7 by performing
drainage experiments in mice where they injected a blue, albumin-binding dye into the ear skin of the
mice. Notably, albumin is an endogenous protein, which can only be transported out of the tissue via
the lymphatic vessels. By quantifying the dye that remained in the tissue one day after the injection,
the researchers were able to determine how well the lymphatic drainage worked in these laboratory
animals.
When performing this experiment in mice lacking a functioning IL-7 receptor, they observed that
these mice were only able to remove half as much dye from their ear skin in comparison with mice
possessing a functional IL-7 receptor. By contrast, they observed a considerable increase in lymphatic
drainage in mice with increased IL-7 production. Finally, in a third experiment, they administered IL-7
protein to unmodified, healthy mice and observed that this therapeutic treatment led to an
improvement of lymphatic drainage function.
Already tested in patients
New function for a well-known immune messenger molecule 8/26/13 6:50 PM
http://www.eurekalert.org/pub_releas...-nff082613.php Page 2 of 2
The scientists are now planning to conduct similar experiments in mice in which lymphatic vessels
have been surgically destroyed, similarly to the situation found in patients after cancer surgery. Here,
the researchers would like to test whether treatment with IL-7 could help to prevent lymphedema or
whether IL-7 could even be administered in order to reduce existing lymphedema.
The long-term goal is to explore the potential of an IL-7-based medication for lymphedema. Notably,
IL-7 is already being tested in clinical trials, albeit for different indications: because of its immunestimulatory
activity on T cells, IL-7 is currently being tested in patients with immunodeficiency
diseases, such as HIV, or hepatitis infections, or who have undergone bone-marrow transplantations.
###
Literature reference
Iolyeva M, Aebischer D et al.: Interleukin-7 is produced by afferent lymphatic vessels and supports
lymphatic drainage. Blood, 2013, published ahead of print, doi: 10.1182/blood-2013-01-478073
EVEN HOTTER OFF THE PRESS--
Plast Reconstr Surg. 2013 Sep;132(3):580-9. doi: 10.1097/PRS.0b013e31829ace13.
Molecular analysis and differentiation capacity of adipose-derived stem cells from lymphedema tissue.
Levi B, Glotzbach JP, Sorkin M, Hyun J, Januszyk M, Wan DC, Li S, Nelson ER, Longaker MT, Gurtner GC.
Source
Stanford, Calif. From the Hagey Laboratory for Pediatric Regenerative Medicine; Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine; and the Institute for Stem Cell Biology and Regenerative Medicine, Stanford University.
Abstract
BACKGROUND:
Many breast cancer patients are plagued by the disabling complication of upper limb lymphedema after axillary surgery. Conservative treatments using massage and compression therapy do not offer a lasting relief, as they fail to address the chronic transformation of edema into excess adipose tissue. Liposuction to address the adipose nature of the lymphedema has provided an opportunity for a detailed analysis of the stromal fraction of lymphedema-associated fat to clarify the molecular mechanisms for this adipogenic transformation.
METHODS:
Adipose-derived stem cells were harvested from human lipoaspirate of the upper extremity from age-matched patients with lymphedema (n = 3) or subcutaneous adipose tissue from control patients undergoing cosmetic procedures (n = 3). Immediately after harvest, adipose-derived stem cells were analyzed using single-cell transcriptional profiling techniques. Osteogenic, adipogenic, and vasculogenic gene expression and differentiation were assessed by quantitative real-time polymerase chain reaction and standard in vitro differentiation assays.
RESULTS:
Differential transcriptional clusters of adipose-derived stem cells were found between lymphedema and subcutaneous fat. Interestingly, lymphedema-associated stem cells had a much higher adipogenic gene expression and enhanced ability to undergo adipogenic differentiation. Conversely, they had lower vasculogenic gene expression and diminished capability to form tubules in vitro, whereas the osteogenic differentiation capacity was not significantly altered.
CONCLUSIONS:
Adipose-derived stem cells from extremities affected by lymphedema appear to exhibit transcriptional profiles similar to those of abdominal adipose-derived stem cells; however, their adipogenic differentiation potential is strongly increased and their vasculogenic capacity is compromised. These results suggest that the underlying pathophysiology of lymphedema drives adipose-derived stem cells toward adipogenic differentiation.
PMID: 23985633 [PubMed - in process]