Erythropoietin Improves the Survival of Fat Tissue after Its Transplantation in Nude Mice

Abstract

BackgroundAutologous transplanted fat has a high resorption rate, providing a clinical challenge for the means to reduce it. Erythropoietin (EPO) has non-hematopoietic targets, and we hypothesized that EPO may improve long-term fat graft survival because it has both pro-angiogenic and anti-apoptotic properties. We aimed to determine the effect of EPO on the survival of human fat tissue after its transplantation in nude mice.Methodology/Principal FindingsHuman fat tissue was injected subcutaneously into immunologically-compromised nude mice, and the grafts were then treated with either 20 IU or 100 IU EPO. At the end of the 15-week study period, the extent of angiogenesis, apoptosis, and histology were assessed in the fat grafts. The results were compared to vascular endothelial growth factor (VEGF)-treated and phosphate-buffered saline (PBS)-treated fat grafts. The weight and volume of the EPO-treated grafts were higher than those of the PBS-treated grafts, whose weights and volumes were not different from those of the VEGF-treated grafts. EPO treatment also increased the expression of angiogenic factors and microvascular density, and reduced inflammation and apoptosis in a dose-dependent manner in the fat grafts.Conclusions/SignificanceOur data suggest that stimulation of angiogenesis by a cluster of angiogenic factors and decreased fat cell apoptosis account for potential mechanisms that underlie the improved long-term survival of fat transplants following EPO treatment.

Erythropoietin administration partially prevents adipose tissue loss in experimental cancer cachexia models

“…Moreover, intramuscular EPO administration after crush injury of rat skeletal muscle induces a faster and better regeneration with improved microcirculation ( 15 ). Besides the skeletal muscle, the adipose tissue, which is strongly affected during cachexia, has been recently suggested as target of EPO action ( 16 ). Indeed, EPO administration to nude mice previously transplanted with human fat tissue determined longer survival and stimulated angiogenesis of the grafts; these effects were comparable to those exerted by the proangiogenic protein vascular endothelial growth factor (VEGF) ( 16 ).…”

“…Animals were randomized and divided into two groups, namely, controls (C) and tumor bearers (C26). C26 were divided into two subgroups: untreated and treated every three days with an intraperitoneal injection of recombinant human EPO (100 IU, Calbiochem), adopting the same protocol of a previous work ( 16 ). Mice were euthanized under anesthesia 14 days after tumor implantation.…”

Application of Platelet-Rich Plasma and Platelet-Rich Fibrin in Fat Grafting: Basic Science and Literature Review

“…[3][4][5][6][7][8] Among these, plateletrich plasma (PRP) has recently emerged as a new matrix to enhance fat graft survival. PRP, which is derived from whole blood through double-spin centrifugation, contains multiple growth factors and adhesion molecules in a-granules.…”

Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

“…They suggest that adult human adipose tissue does not have the capacity for suffi cient angiogenesis to support adipocyte survival ( 26,27 ). Successful human adult adipose tissue xenotransplantation has involved supplementation of mice with proangiogenic growth factors, such as neuropeptide Y and erythropoietin ( 15,16 ). One adult adipose tissue transplant study found that vascularization of the implanted fat originated from neighboring host vessels ( 26 ).…”

“…or induced overexpression of proangiogenic, prosurvival agents ( 15,16 ), xenotransplantation has not been utilized as an approach to study adipogenesis or adipose tissue remodeling. With this circumstance in mind, and with a particular interest in studying the fetal epigenetic programming of adipose tissue development, we explored the xenotransplantation of midgestation human fetal adipose tissue into immunocompromised rodents.…”