[[stem_cell_therapy_for_lymphedema]]
 
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— stem_cell_therapy_for_lymphedema 2009/09/11 06:19 current
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 +======Stem Cell Therapy for Lymphedema======
 +
 +As research continues and our longing increases to find a cure for lymphedema, this study was sent to me by a membe of our [[http://health.groups.yahoo.com/group/childrenwithlymphedema/ |Children with Lymphedema Yahoo Support Group]].
 +
 +I attempted to access the original site it came from in Cuba, but was unfortunately blocked, either by Google or by some Cuban governmental restriction.  Never the less, I thought it important enough to post.
 +
 +There is the possibility that this can be of tremendous value to us and I can only hope that researchers in the United States or other countries will move quickly into this new area of study.
 +
 +As I can find further information, I will immediately update this page.
 +
 +[[My Life with Lymphedema|Pat O'Connor]]
 +
 +September 11, 2009
 +
 +======Autologous stem cell implantation from Peripheral Blood in Patients with Chronic Lower Limb Lymphedema======
 +
 +September 10, 2009
 +
 +Goicoechea Díaz P, Artaza Sanz HM, Blanco Díaz A, García Pelegrin S, Atencio Sariol E, Hernández Ramírez P1, González Suárez T1, Matamoros Martínez de Pinillos MA1, Socarrás Ferrer BB1, del Valle Pérez L1, Peña Quian Y2, Pintado Perera A2.
 +
 +Hospital Clínico Quirúrgico Docente “Enrique Cabrera”. La Habana, 1Instituto de
 +Hematología e Inmunología. La Habana, 2Centro de Investigaciones Clínicas. La Habana. Cuba.
 +[[pedro.goicoechea@infomed.sld.cu]]
 +
 +Lymphedema is a chronic disease characterized by abnormal accumulation of lymph due to a failure of the lymphatic system, which can affect the upper limbs, lower and external genitalia. The lymphedema are classified as primary if they have no identifiable cause defects if present from birth, early or late depending on the age at which they appear and side, those with an identifiable cause, including those appearing post -lymphangitis, post radiation, for filariasis.
 +
 +In this study, we evaluated in patients with lower limb lymphedema in the efficacy of autologous stem cell implants derived from bone marrow and mobilized peripheral blood by stimulation with granulocyte colony stimulating factor.
 +
 +We treated 6 patients, 3 men and 3 women, mean age 48 years, all with lymphedema in both lower limbs by recurrent lymphangitis. We performed the implantation of stem cells in the most affected leg. The injections were made at a distance of 3 cm between them and a volume of 1 ml per puncture, varying the total volume according to the intensity and extent of lymphedema. In all cases there has been a progressive decrease in diameter of the injected limb and has been an improvement in the evolutionary lymphography performed.
 +
 +We believe this approach is an alternative method to treat this disease, which over the years has not benefited from the treatment methods normally used.
 +
 +1. [[http://www.sld.cu/sitios/medregenerativa/temas.php?idv=25685
 +|Medicina Regenerativa en Cuba]]
 +
 +======Background information======
 +
 +======Early lymph vessel development from embryonic stem cells.======
 +
 +Kreuger J, Nilsson I, Kerjaschki D, Petrova T, Alitalo K,
 +Claesson-Welsh L.
 +
 +Department of Genetics and Pathology, Uppsala University, Sweden.
 +[[johan.kreuger@genpat.uu.se]]
 +
 +**OBJECTIVE:** The purpose of this study was to establish a model system for lymph vessel development based on directed differentiation of murine embryonic stem cells.
 +
 +**METHODS AND RESULTS:** Stem cells were aggregated to form embryoid bodies, and subsequently cultured in 3-dimensional collagen matrix for up to 18 days. Treatment with vascular endothelial growth factor (VEGF)-C and VEGF-A individually enhanced formation of lymphatic vessel structures, although combined treatment with VEGF-C and VEGF-A was most potent and gave rise to a network of LYVE-1, podoplanin, Prox1, and VEGF receptor-3 positive lymphatic vessel structures running parallel to and apparently emanating from, capillaries. In contrast, fibroblast growth factor-2, hepatocyte growth factor, or hypoxia had little or no effect on the development of the early lymphatics.
 +
 +Further, cells of hematopoietic origin were shown to express lymphatic markers. In summary, different subpopulations of lymphatic endothelial cells were identified on the basis of differential expression of several lymphatic and blood vessel markers, indicating vascular heterogeneity.
 +
 +**CONCLUSIONS:** We conclude that the present model closely mimics the early steps of lymph vessel development in mouse embryos.
 +
 +Full Text Article [[http://atvb.ahajournals.org/cgi/content/full/26/5/1073|American Heart Association]]
 +
 +======Differentiation of Lymphatic Endothelial Cells From Embryonic Stem Cells on OP9 Stromal Cells.======
 +
 +Kono T, Kubo H, Shimazu C, Ueda Y, Takahashi M, Yanagi K, Fujita N,
 +Tsuruo T, Wada H, Yamashita JK.
 +
 +Molecular and Cancer Research Unit, HMRO and Department of Thoracic
 +Surgery, Graduate School of Medicine, Kyoto University, Japan;
 +Laboratory of Stem Cell Differentiation, Stem Cell Research Center,
 +Institute for Frontier Medical Sciences, Kyoto University, Japan;
 +Institute of Molecular and Cellular Biosciences, The University of
 +Tokyo, Japan; and PRESTO, Japan Science and Technology Agency, Japan.
 +
 +Correspondence to Hajime Kubo, Molecular and Cancer Research Unit, HMRO, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan. E-mail [[kuboflt@kuhp.kyoto-u.ac.jp]]; or Jun K. Yamashita, Laboratory of Stem Cell Differentiation, Institute for Frontier Medical Sciences, Kyoto University, Shogoin-Kawahara-cho53, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail [[juny@frontier.kyoto-u.ac.jp]]
 +
 +**OBJECTIVE:** The discovery of vascular endothelial growth factor C
 +(VEGF-C) and VEGF receptor-3 (VEGFR-3) has started to provide an
 +understanding of the molecular mechanisms of lymphangiogenesis. The
 +homeobox gene prox1 has been proven to specify lymphatic endothelial
 +cells (ECs) from blood ECs. We investigated the process of lymphatic EC
 +(LEC) differentiation using embryonic stem (ES) cells.
 +
 +**METHODS AND RESULTS:** VEGFR-2(+) cells derived from ES cells
 +differentiated into LECs at day 3 on OP9 stromal cells defined by the
 +expression of prox1, VEGFR-3, and another lymphatic marker podoplanin.
 +VEGFR-2(+) cells gave rise to LYVE-1(+) embryonic ECs, which were
 +negative for prox1 on day 1 but turned to prox1(+) LECs by day 3.
 +VEGFR-3-Fc or Tie2-Fc, sequestering VEGF-C or angiopoietin1 (Ang1),
 +suppressed colony formation of LECs on OP9 cells. However, addition of
 +VEGF-C and Ang1 in combination with VEGF to the culture of VEGFR-2(+)
 +cells on collagen-coated dishes failed to induce LECs. LEC-inducing
 +activity of OP9 cells was fully reproduced on paraformaldehyde-fixed
 +OP9 cells with the conditioned medium.
 +
 +**CONCLUSIONS:** We succeeded in differentiating LECs from ES cells and revealed the requirements of VEGF-C, Ang1, and other unknown factors for LEC differentiation.
 +
 +PMID: 16690875 [PubMed - as supplied by publisher]
 +
 +Full Text Article [[http://atvb.ahajournals.org/cgi/content/full/26/9/2070|American Heart Association]]
 +
 +======A chemically defined culture of VEGFR2+ cells derived from embryonic stem cells reveals the role of VEGFR1 in tuning the threshold for VEGF in developing endothelial cells.======
 +
 +Hirashima M, Ogawa M, Nishikawa S, Matsumura K, Kawasaki K, Shibuya M, Nishikawa S.
 +Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Japan.
 +
 +Vascular endothelial growth factor (VEGF) is a major growth factor for developing endothelial cells (ECs). Embryonic lethality due to haploinsufficiency of VEGF in the mouse highlighted the strict dose dependency of VEGF on embryonic vascular development. Here we investigated the dose-dependent effects of VEGF on the differentiation of ES cell-derived fetal liver kinase 1 (Flk-1)/VEGF receptor 2(+) (VEGFR2(+)) mesodermal cells into ECs on type IV collagen under a chemically defined serum-free condition. These cells could grow even in the absence of VEGF, but differentiated mostly into mural cells positive for alpha-smooth muscle actin.
 +
 +VEGF supported in a dose-dependent manner the differentiation into ECs defined by the expression of VE-cadherin, platelet-endothelial cell adhesion molecule 1 (PECAM-1)/ CD31, CD34, and TIE2/TEK. VEGF requirement was greater at late than at early phase of culture during EC development, whereas response of VEGFR2(+) cells to VEGF-E, which is a virus-derived ligand for VEGFR2 but not for Flt-1/VEGFR1, was not dose sensitive even at late phase of culture. Delayed expression of VEGFR1 correlated with increased dose dependency of VEGF.
 +
 +These results suggested that greater requirement of VEGF in the maintenance than induction of ECs was due to the activity of VEGFR1 sequestering VEGF from VEGFR2 signal. The chemically defined serum-free culture system described here provides a new tool for assessing different factors for the proliferation and differentiation of VEGFR2(+) mesodermal cells.
 +
 +Full text article [[http://www.bloodjournal.org/cgi/content/full/101/6/2261|Journal of the American Society of Hematology]]
 +
 +====== ARTICLES FROM OUR FORUM ON LEG LYMPHEDEMA ======
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=53 | Silkie's Story]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=28 | Leg Lymphedema 2006 Abstracts]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=269 | Quality of Life in Patients with Lymphedema of Lower Limb]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=270 | Lymphscintigraphic evaluation MLD for lower limb lymphedema]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=271 | Management of lower limb lymphedema in the United Kingdom]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=517 | Arthritis of the knees and lymphedema]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=535 | Right Leg Lymphedema]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=817 | Multilayer Compression Bandaging of the Lymphedema Leg]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=954 | Leg Lymphedema in women after treatment gynecological cancer]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=959 | Farrow Wraps 1.]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=962 | Restless Leg Syndrome]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=58 | Why Compression Pumps Cause Damage]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=155 | The Flexitouch Device - Initial Observations]]
 +
 +[[http://www.lymphedemapeople.com/phpBB3/viewtopic.php?t=200 | Complications of Lymphedema Debulking Surgery]]
 +
 +====== IMAGES ======
 +
 +{{leglymph4.jpg |}} {{leglymph5.jpg |}} {{leglymph6.jpg |}}  {{leglymph7.jpg |}}  {{leglymph8.jpg |}}
 +
 +{{footlymph1.jpg |}} {{footlymph2.jpg |}}
 +
 +======Lymphedema People Resources======
 +
 +[[Lymphedema People Forums]]
 +
 +[[Lymphedema People Blogs]]
 +
 +[[Lymphedema People Glossaries]]
 +
 +[[Lymphedema People Online Support Groups]]
 +
 +  * [[Privacy Statement]]
 +
 +  * [[Terms of Use]]
 +
 +  * [[Rules of Conduct]]
 +
 +  * Contact:
 +
 +[[lymphedemapeople@aol.com]]
 +
 +[[lymphedemapeople@yahoo.com]]
 
stem_cell_therapy_for_lymphedema.txt · Last modified: 2009/09/11 06:19 by patoco
 
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