Faculty Bibliography

GENERAL PURPOSE: To provide information about hyperbaric oxygen therapy (HBOT), its mechanisms, indications and safe applications based on clinical evidence. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant should be better able to:1. Recall the physiology of wound healing and the mechanisms of action of HBOT.2. Identify current applications of HBOT based on clinical evidence as well as its risks and contraindications. ABSTRACT: Treating chronic wounds and infections are challenging medical problems worldwide. Hyperbaric oxygen therapy (HBOT), the administration of 100% oxygen at pressures greater than 1.4 atmosphere absolute in a series of treatments, can be used as an adjunctive therapy in many wound care settings because it improves oxygenation and neovascularization and decreases inflammation in chronic wounds. A growing number of studies support the benefits of HBOT for enhancing wound healing and decreasing the likelihood of negative events such as amputation. However, many practitioners are unfamiliar with HBOT. This article provides a general introduction to HBOT, reviews the physiology and mechanisms of behind HBOT, discusses all the indications for HBOT, and explores in-depth the clinical evidence for HBOT in the treatment of arterial insufficiencies, diabetic ulcers, delayed radiation injury, and chronic refractory osteomyelitis.

BACKGROUND: Fat grafting has become popular for repair of postsurgical/postradiation defects after head/neck cancers resection. Fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve graft viability/efficacy, although the impact of ASCs on head/neck cancer cells is unknown. OBJECTIVES: To determine whether ASCs affect growth, migration, and metastasis of human head/neck cancer. METHODS: Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured human ASCs, or treated with ASC conditioned medium (CM), and cancer cell growth/migration was assessed by MTT, cell count, and scratch/wound healing assays in vitro. Co-injection of 3 x 10(6) Cal-27/green fluorescent protein (GFP) cells and ASCs into the flank of NUDE mice assessed ASC effect on tumor growth/morphology. Quantitation of human chromosome 17 DNA in mouse organs assessed ASC effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry. RESULTS: Co-culture of Cal-27 or SCC-4 cells with ASCs from 2 different donors or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs from 2 different donors with Cal-27 cells did not affect tumor volume at 6 weeks, but increased Cal-27 micrometastasis to the brain. Evaluation of tumors sections from 1 ASC donor co-injection revealed that ASCs were viable and well integrated with Cal-27/GFP cells. These tumors exhibited increased MMP2, MMP9, IL-8, and microvessel density. CONCLUSIONS: Human ASCs did not alter growth of human head/neck cancer cells or tumor xenografts, but stimulated migration and early micrometastasis to mouse brain.

Tracheostoma wounds are complex defects that commonly occur in patients with vessel-depleted necks after cervical lymphadenectomy, who have multiple medical comorbidities, and a history of radiation therapy. The authors report reconstruction of 5 tracheostoma wounds using a pedicled, supraclavicular artery island flap as a reconstructive alternative. There were no flap losses, fistulas or leaks, revisions, or other complications. The supraclavicular artery island flap is a versatile, reliable, and effective option for tracheostoma reconstruction.

Found in most mesenchymally derived organs, mesenchymal stem cells are undifferentiated cells capable of developing into many cell types. Adipose stem cells are a type of mesenchymal stem cell easily extracted from lipoaspirate, often readily available, and are conformable to the tissue defect. Their ability for self-renewal, unlimited proliferation and proangiogenic, and immunomodulatory properties have made them attractive adjuncts in plastic surgery. Since the discovery of pluripotent cells in adipose tissue, plastic surgeons have applied the technology toward improving wound healing, soft tissue augmentation, and tissue engineering. More recently, some surgeons have used adipose stem cells in cancer reconstruction. By mixing lipoaspirate with concentrated fractions of adipose stem cells through a technique termed cell-assisted lipotransfer, plastic surgeons have claimed improved aesthetic results. Promising early results have been tempered by in vitro and animal studies demonstrating increased tumor proliferation and metastasis rates with the use of adipose and other mesenchymal stem cells. This review provides a succinct yet comprehensive overview of the current literature evaluating the oncologic risks associated with adipose stem cell use in cancer.

BACKGROUND: Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a human breast cancer model that exhibits early metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Human MDA-MB-231 breast cancer cells represents "triple negative" breast cancer that exhibits early micrometastasis to multiple mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from three healthy female donors. Indirect co-culture of MDA-MB-231 cells with ASCs, as well as direct co-culture demonstrated that ASCs had no effect on MDA-MB-231 growth. Indirect co-culture, and ASC conditioned medium (CM) stimulated migration of MDA-MB-231 cells. ASC/RFP cells from two donors co-injected with MDA-MB-231/GFP cells exhibited a donor effect for stimulation of primary tumor xenografts. Both ASC donors stimulated metastasis. ASC/RFP cells were viable, and integrated with MDA-MB-231/GFP cells in the tumor. Tumors from the co-injection group of one ASC donor exhibited elevated vimentin, matrix metalloproteinase-9 (MMP-9), IL-8, VEGF and microvessel density. The co-injection group exhibited visible metastases to the lung/liver and enlarged spleen not evident in mice injected with MDA-MB-231/GFP alone. Quantitation of the total area of GFP fluorescence and human chromosome 17 DNA in mouse organs, H&E stained paraffin sections and fluorescent microscopy confirmed multi-focal metastases to lung/liver/spleen in the co-injection group without evidence of ASC/RFP cells. CONCLUSIONS: Human ASCs derived from abdominal lipoaspirates of two donors stimulated metastasis of MDA-MB-231 breast tumor xenografts to multiple mouse organs. MDA-MB-231 tumors co-injected with ASCs from one donor exhibited partial EMT, expression of MMP-9, and increased angiogenesis.

BACKGROUND:Obesity is associated with a higher risk of developing cancer and co-morbidities that are part of the metabolic syndrome. Adipose tissue is recognized as an endocrine organ, as it affects a number of physiological functions, and contains adipose tissue-derived stem cells (ASCs). ASCs can differentiate into cells of multiple lineages, and as such are applicable to tissue engineering and regenerative medicine. Yet the question of whether ASC functionality is affected by the donor's body mass index (BMI) still exists. RESULTS:ASCs were isolated from patients having different BMIs (BMI-ASCs), within the ranges of 18.5-32.8. It was hypothesized that overweight BMI-ASCs would be more compromised in early adipogenic and osteogenic potential, and ability to form colonies in vitro. BMI was inversely correlated with ASC proliferation and colony forming potential as assessed by CyQUANT proliferation assay (fluorescence- based measurement of cellular DNA content), and colony forming assays. BMI was positively correlated with early time point (day 7) but not later time point (day 15) intracytoplasmic lipid accumulation as assessed by Oil-Red-O staining. Alizarin red staining and RT-PCR for alkaline phosphatase demonstrated that elevated BMI resulted in compromised ASC mineralization of extracellular matrix and decreased alkaline phosphatase mRNA expression. CONCLUSIONS:These data demonstrate that elevated BMI resulted in reduced ASC proliferation, and potentially compromised osteogenic capacity in vitro; thus BMI is an important criterion to consider in selecting ASC donors for clinical applications.

Behcet's disease (BD) is an autoimmune & autoinflammatory disease of unclear etiology characterized by recurrent oral & genital ulcers as well as other systemic manifestations. A key pathogenesis is excessive inflammatory wound healing response. While descriptions of the cutaneous manifestations of disease are limited to short-term consequences such as extensive pustule and papule formation in response to minor tissue injury, the long-term consequences are significant fibrosis and scarring of epithelial tissue. We describe the case of a patient with Behcet's disease who presented with unilateral facial atrophy secondary to minor trauma to the oral mucosa. She was treated with autologous fat grafting. Though a rare disease, plastic surgeons should be aware of the entity of Behcet's disease and its complications of tissue atrophy that may require reconstructive surgery.