Adipose stem cells are considered one of the primary drivers of autologous fat graft biological activity and survival. We have previously demonstrated that hormonally active VD3 improved adipose stem cell viability in ex vivo and in vivo fat grafting models. In this study, we evaluated the inactive form of VD3 (cholecalciferol) on adipose stromal cell (ASC) phenotype during hypoxia and the subsequent effect on human fat graft retention in the xenograft model. Lipoaspirate collected from six human donors was used for ex vivo particle culture studies and isolated ASC studies. Adipose particles were treated with increasing doses of VD3 to determine impact on ASC survival. Expanded stromal cells were treated with VD3 during hypoxic culture and assessed for viability, apoptosis, mitochondrial activity, and nitric oxide (NO) release via caspase, DAF-FM, or TMRM. Finally, 40 Nu/J mice receiving bilateral dorsal human lipoaspirate were treated thrice weekly with (1) vehicle control, (2) 50 ng calcitriol, (3) 50 ng VD3, (4) 500 ng VD3, and (5) 5,000 ng VD3 for 12 weeks, n = 8 per group. Graft weight, volume, and architecture were analyzed. Adipose particles treated with dose-escalating VD3 had significantly increased ASC viability compared with control ( P < 0.01). Under hypoxia, ASCs treated with 1 nM VD3 had significantly greater viability than untreated and pretreated cells ( P < 0.01, P < 0.01) and significantly lower apoptosis-to-viability ratio ( P < 0.01). ASCs pretreated with 1 nM VD3 had significantly lower NO release ( P < 0.05) and lower mitochondrial polarization ( P < 0.05) compared with controls. In vivo results showed mice receiving 5,000 ng VD3 had significantly greater graft weight ( P < 0.05) and volume ( P < 0.05) after 12 weeks of treatment compared with controls. Grafts had enhanced neovascularization, intact adipocyte architecture, and absence of oil cysts. VD3 is an over-the-counter nutritional supplement with a known safety profile in humans. Our xenograft model suggests administering VD3 at the time of surgery may significantly improve fat graft retention.

Background/Objectives: Assigned female at birth (AFAB) individuals who identify as transgender or gender-diverse (TGD) with concurrent breast cancer or high-risk genetic mutations represent a unique population, requiring consideration of oncologic and aesthetic goals. These patients sought chest masculinization with oncologic gender-affirming mastectomy (OGAM) or non-binary reconstruction to alleviate gender dysphoria and treat their breast cancer. There is limited literature on surgical techniques in this patient population. Methods: A retrospective chart review of AFAB TGD adults (>18 years of age) who underwent OGAM or non-binary reconstruction at the University of Washington between 2019 and 2023 was conducted. All patients had a consultation with a plastic surgeon for reconstruction and a minimum of one year follow-up. Demographic data, oncologic status, post-operative complications, and revision surgical history were collected. Results: Eight AFAB TGD individuals met the inclusion criteria. The mean age at the time of mastectomy was 35.13 years (SD = 8.04), and the mean BMI was 29.88 (SD = 6.40). Indications for mastectomy included a breast cancer diagnosis (N = 4) or a strong family history of breast cancer or genetic predisposition (N = 4). Two (25%) patients underwent nipple-sparing mastectomies (NSM), two patients (25%) underwent skin-sparing mastectomy with Goldilocks reconstruction, and four patients (50%) underwent simple mastectomy (oncologic gender-affirming mastectomy), flat closure with free nipple graft (FNG). Two patients had staged nipple mastectomy with secondary nipple reduction and fat grafting. Six patients had immediate reconstruction, four (50%) patients underwent immediate double-incision OGAM with FNG, and two (25%) patients underwent Goldilocks procedures—one with and one without FNG. One patient (12.5%) experienced a surgical site infection, and three patients (37.5%) underwent revision surgery. No patients had positive margins following their mastectomy. Conclusions: This case series highlights the importance of a multidisciplinary and highly personalized approach for AFAB and TGD individuals undergoing oncologic gender-affirming mastectomy or non-binary reconstruction. We reviewed reconstructive options performed at our institution, demonstrating safe oncologic and reconstructive techniques that emphasized collaboration between breast and plastic surgeons.