Stem cell policy as a curative plan of lymphedema in breast cancer patients Kamran Mansouri Medical Biology Research Center Kermanshah University of Medical Sciences

Autologous fat grafting or lipofilling has completely changed the management of soft tissue defects in the last 20 years. Lipofilling was first described over a century ago and is now seen as an ideal filler, because it is host-compatible, easily and repeatedly harvested, with good results and a low complication rate. Over the years this technique has been further improved, and since the 1990s the most frequently used technique is Coleman’s procedure.

autologous fat grafting is associated with a significant fat graft resorption rate. The fat survival rate varies from 20% to 80% in the literature . In addition, local ischemia in the recipient site can lead to the two characteristic complications of autologous fat grafts; adipo-cyte necrosis and consequent volume loss. This initial ischemia limits the fat engraftment and requires several surgical procedures to obtain an optimal result.

The main indications for lipofilling are the correction of contour defects after trauma, cancer, radiotherapy, or for purely aesthetic reasons. Because of the inconstant and sometimes low survival rates associated with lipofilling, researchers have tried to increase the vascularization of the graft with multiple products, such as insulin , vascular endothelial growth factor (VEGF) , platelet rich plasma (PRP) , and also by enriching the fat with stromal cells. These stromal cells are known for their angiogenic properties .

This procedure defines cell-assisted lipotransfer (CAL), an autologous fat transfer enriched with stromal cells. Update on Adipose-derived Stromal Cells (ASC) Mesenchymal stromal cells (MSC) were described for the first time in the bone marrow (BM-MSC) in the 1970s by Friedenstein . Cells with capabilities and characteristics similar to BM-MSC have been found in the stroma of many other organs and tissues , including adipose tissue. Adipose tissue can be obtained in a minimally invasive way via liposuction, whereas BM aspiration is an invasive procedure associated with higher morbidity. Moreover, adipose tissue has a higher MSC yield compared to bone marrow.

Adipose-derived stromal cells (ASC) are present in large amounts in the stromal vascular fraction (SVF) obtained after enzymatic digestion of the lipoaspirate. The SVF contains ASC as well as a heterogenous cell population, such as hematopoietic stem cells, endothelial cells and pericytes. They also present better pro-angiogenic properties compared to BM-MSC and can be an interesting tool for treatment of acute ischemia of the lower limbs. The ASC express markers in common with other mesenchymal stromal cells (MSC), including CD105, CD73, CD90, and are negative for CD31 and the CD45 . In contrast to BM-MSC, ASC express the CD34 marker (present in the SVF fraction), which decreases after several passages in culture

These cells are also capable of modulating the inflammatory and immune response , which has made them new tools in regenerative medicine for the treatment of autoimmune and inflammatory diseases. ASC contained in the SVF, may improve fat survival. Indeed, as described previously, ASC can differentiate into adipocyte or endothelial cells and promote vascularization and regeneration of the fat. ASC may remain as original ASC in the graft and release paracrine factors such as HGF or SDF-1 that can promote angiogenesis and help the surrounding tissue resist hypoxia and ischemia.

The recent decline in breast cancer mortality might be due to prevention or to screening mammography or to improved treatment protocols. We sought to determine which factors are likely to be responsible for the observed decline in breast cancer mortality.

Lymphedema: Lymphedema is a progressive disorder characterized by abnormal accumulation of protein rich fluid in the interstitial space. Five-year cumulative incidence of lymphedema was 42 (42%) per 100 women. In breast cancer, lymphedema is due to treatment-induced mechanical insufficiency of the lymphatic system.

Radiation Axillary Node Dissection Arm infection/injury Weight gain since operation Chemotherapy ** Tamoxifen ** Marital status **

The Psycho-Social Impact of Lymphedema. Many studies have reported short and long term reduction in quality of life during and following treatment for breast cancer . The Psycho-Social Impact of Lymphedema. At 3 months, < 30 % of patients have returned to normal activities of daily living (Gosselink, 2003) Approximately ½ of women report difficulty lifting, carrying and sleeping at 1 year post-surgery (Karki, 2005)

In the developed world, cancer treatment is the leading cause of lymphedema. It is a debilitating condition associated with recurrent infections and reduced quality of life . The present standard of care is compression therapy, which depends on continuous adherence to be effective . Accordingly, new therapeutic approaches are needed to treat this condition. One such approach is stem cell therapy.

Complications after the CAL technique the same complications after the CAL technique as after conventional lipofilling. The main complications were oil cysts, followed by fat necrosis, calcifications, nodules and fibrosis.

SVFwas characterized by nucleated cell count and viability, the percentage of fibroblastoid colony-forming units (CFU-F), and surfacemarker analysis using the following markers fromBDBiosciences (Albertslund,Denmark, http://www.bd.com): anti-CD34 (PE-CF594, clone 581), anti- CD45 (fluorescein isothiocyanate, clone HI30), CD31 (Alexa Fluor 647, clone WM59), CD73 (allophycocyanin [APC], clone AD2), CD90 (APC, clone 5E10),