Background Postmastectomy radiotherapy is considered to be a necessary treatment in the therapy of breast cancer, while it will cause soft tissue damage and complications, which are closely related to the success rate and effectiveness of breast reconstruction. After radiotherapy, cutaneous tissue becomes thin and brittle, and its compliance decreases. Component fat grafting and adipose-derived stem cell therapy are considered to have great potential in treating radiation damage and improving skin compliance after radiotherapy. Main body In this paper, the basic types and pathological mechanisms of skin and soft tissue damage to breast skin caused by radiation therapy are described. The 2015–2021 studies related to stem cell therapy in PubMed were also reviewed. Studies suggest that adipose-derived stem cells exert their biological effects mainly through cargoes carried in extracellular vesicles and soluble secreted factors. Compared to traditional fat graft breast reconstruction, ADSC therapy amplifies the effects of stem cells in it. In order to obtain a more purposeful therapeutic effect, proper stem cell pretreatment may achieve more ideal and safe results. Conclusion Recent research works about ADSCs and other MSCs mainly focus on curative effects in the acute phase of radiation injury, and there is little research about treatment of chronic phase complications. The efficacy of stem cell therapy on alleviating skin fibrosis and its underlying mechanism require further research.
Excess and dysfunctional adipose tissue plays an important role in metabolic diseases, including obesity, atherosclerosis and type 2 diabetes mellitus. In mammals, adipose tissue is categorized into two types: white and brown. Adult brown tissue is mainly composed of beige adipocytes, which dispose of stored energy as heat and have become increasingly popular as a therapeutic target for obesity. However, there is still a paucity of cell models that allow transdifferentiation of mature white adipocytes into beige adipocytes, as seen in vivo. Here, we describe a novel, ceiling culture-based model of human mature white adipocytes, which transdifferentiate into beige adipocytes under the mechanical force and hypoxia of ceiling culture. We also show that the use of rosiglitazone and rapamycin can modulate transdifferentiation, up and down regulating expression of beige adipocyte-specific genes, respectively. Rosiglitazone additionally facilitated the upregulation of fatty acid lipolysis and oxidation genes. Finally, these beige adipocytes derived from dedifferentiated adipocytes exhibited a progenitor-specific phenotype, with higher expression of mature adipocyte-specific genes than adipocyte-derived stem cells. Overall, we report a novel approach to conveniently cultivate beige adipocytes from white adipocytes in vitro, suitable for mechanistic studies of adipose biology and development of cell and drug therapies in the future.
In the past four decades, breast cancer incidence rates have risen dramatically, and during 2010 to 2019, the rate increased by 0.5% annually. In 2022, approximately 287,850 new cases of invasive breast cancer will be diagnosed among U.S. women, and 43,250 women will die from breast cancer. 1 In 2018, 63% of patients with stage I or II disease underwent breast-conserving surgery, and 33% underwent mastectomy. 2 Background: Fat grafting has an unsatisfactory retention rate for breast reconstruction because of poor recipient conditions. The contribution of the recipient site to fat grafts is unknown. In this study, the authors hypothesize that tissue expansion could improve fat graft retention by preconditioning the recipient fat pad. Methods: Overexpansion was achieved using 10-mL cylindrical soft-tissue expanders implanted beneath the left inguinal fat flaps of 16 Sprague-Dawley rats (weighing 250 to 300 g), whose contralateral parts were implanted with a silicone sheet as a control. After 7 days of expansion, the implants were removed and both inguinal fat flaps received 1 mL of fat grafts from eight donor rats. Fluorescent dye-labeled mesenchymal stromal cells were injected into rats and tracked in vivo by fluorescence imaging. Transplanted adipose tissue was harvested at 4 and 10 weeks (n = 8 per time point). Results: After 7 days of expansion, OCT4 + (P = 0.0002) and Ki67 + (P = 0.0004) areas were increased with up-regulated expression of CXCL12 in recipient adipose flaps. An increasing number of CM-DiI-positive mesenchymal stromal cells were observed in the expanded fat pad. At 10 weeks after fat grafting, retention rate, measured using the Archimedes principle, was much higher in the expanded group than in the nonexpanded group (0.3019 ± 0.0680 versus 0.1066 ± 0.0402; P = 0.0005). Histologic and transcriptional analyses revealed that angiogenesis was enhanced, and macrophage infiltration was decreased in the expanded group. Conclusion: Internal expansion preconditioning increased circulating stem cells into the recipient fat pad and contributed to improved fat graft retention.
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