Michelle Griffin

Ovarian cancer screening—Current status, future directions☆

Evidence of a mortality benefit continues to elude ovarian cancer (OC) screening. Data from the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial which used a screening strategy incorporating CA125 cut-off and transvaginal ultrasound has not shown mortality benefit. The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is using the Risk of Ovarian Cancer (ROC) time series algorithm to interpret CA125, which has shown an encouraging sensitivity and specificity however the mortality data will only be available in 2015. The article explores the impact of growing insights into disease aetiology and evolution and biomarker discovery on future screening strategies. A better understanding of the target lesion, improved design of biomarker discovery studies, a focus on detecting low volume disease using cancer specific markers, novel biospecimens such as cervical cytology and targeted imaging and use of time series algorithms for interpreting markers profile suggests that a new era in screening is underway.

The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery†

The potential use of stem cell‐based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose‐derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.

Systematic review of patient factors affecting adipose stem cell viability and function: implications for regenerative therapy

BackgroundThe applications for fat grafting have increased recently, within both regenerative and reconstructive surgery. Although fat harvesting, processing and injection techniques have been extensively studied and standardised, this has not had a big impact on the variability of outcome following fat grafting. This suggests a possible larger role of patient characteristics on adipocyte and adipose-derived stem cell (ADSC) viability and function. This systematic review aims to collate current evidence on the effect of patient factors on adipocyte and ADSC behaviour.MethodsA systematic literature review was performed using MEDLINE, Cochrane Library and EMBASE. It includes outcomes observed in in vitro analyses, in vivo animal studies and clinical studies. Data from basic science work have been included in the discussion to enhance our understanding of the mechanism behind ADSC behaviour.ResultsA total of 41 papers were included in this review. Accumulating evidence indicates decreased proliferation and differentiation potential of ADSCs with increasing age, body mass index, diabetes mellitus and exposure to radiotherapy and Tamoxifen, although this was not uniformly seen across all studies. Gender, donor site preference, HIV status and chemotherapy did not show a significant influence on fat retention. Circulating oestrogen levels have been shown to support both adipocyte function and graft viability. Evidence so far suggests no significant impact of total cholesterol, hypertension, renal disease, physical exercise and peripheral vascular disease on ADSC yield.ConclusionsA more uniform comparison of all factors highlighted in this review, with the application of a combination of tests for each outcome measure, is essential to fully understand factors that affect adipocyte and ADSC viability, as well as functionality. As these patient factors interact, future studies looking at adipocyte viability need to take them into consideration for conclusions to be meaningful. This would provide crucial information for surgeons when deciding appropriate volumes of lipoaspirate to inject, improve patient selection, and counsel patient expectations with regards to outcomes and likelihood for repeat procedures. An improved understanding will also assist in identification of patient groups that would benefit from graft enrichment and cryopreservation techniques.

The Use of Adipose Stem Cells in Cranial Facial Surgery

Craniofacial malformations, have devastating psychosocial implications for many adults and children and causes huge socioeconomic burden. Currently craniofacial defects require soft tissue transfer, bone grafting techniques or difficult procedures such as microvascular free flaps. Such tissues are often limited in quantity, their harvest causes secondary large donor site defects and they lack the capability to fully restore previous form and function. Stem cell technology is being utilised for various tissue and organs of the body and consequently surgeons are eager to transfer these principles for craniofacial surgery. Adipose derived stem cells (ADSCs) are an exciting stem cell source for craniofacial surgeons due to their easy and painless isolation, relatively large abundance and familiarity with the harvesting procedure. ADSCs also have multiple desirable properties including adipogenic, osteogenic and chondrogenic potential, enhancement of angiogenesis and immunodulatory function. Due to these advantageous characteristics, ASDCs have been explored to repair craniofacial bone, soft tissue and cartilage. The desirable characteristics of ADSCs for craniofacial surgical applications will be explained. We report the experimental and clinical studies that have explored the use of ADSCs for bone, cartilage and soft tissue craniofacial defects. We conclude by establishing the key questions that are preventing the clinical application of ADSCs for craniofacial surgery.

Development of mechano-responsive polymeric scaffolds using functionalized silica nano-fillers for the control of cellular functions

We demonstrate an efficient method to produce mechano-responsive polymeric scaffolds which can alter cellular functions using two different functionalized (OH and NH2) silica nano-fillers. Fumed silica-hydroxyl and fumed silica-amine nano-fillers were mixed with a biocompatible polymer (POSS-PCU) at various wt% to produce scaffolds. XPS and mechanical testing demonstrate that bulk mechanical properties are modified without changing the scaffolds surface chemistry. Mechanical testing showed significant change in bulk properties of POSS-PCU scaffolds with an addition of silica nanofillers as low as 1% (P < 0.01). Scaffolds modified with NH2 silica showed significantly higher bulk mechanical properties compared to the one modified with the OH group. Enhanced cell adhesion, proliferation and collagen production over 14 days were observed on scaffolds with higher bulk mechanical properties (NH2) compared to those with lower ones (unmodified and OH modified) (P < 0.05) during in vitro analysis. This study provides an effective method of manufacturing mechano-responsive polymeric scaffolds, which can help to customize cellular responses for biomaterial applications.

Adipose regeneration and implications for breast reconstruction: update and the future.

The evolution of breast reconstruction and management of breast cancer has evolved significantly since the earliest descriptions in the Edwin Smith Papyrus (3,000 BC). The development of surgical and scientific expertise has changed the way that women are managed, and plastic surgeons are now able to offer a wide range of reconstructive options to suit individual needs. Beyond the gold standard autologous flap based reconstructions, regenerative therapies promise the elimination of donor site morbidity whilst providing equivalent aesthetic and functional outcomes. Future research aims to address questions regarding ideal cell source, optimisation of scaffold composition and interaction of de novo adipose tissue in the microenvironment of breast cancer.

Chemical group-dependent plasma polymerisation preferentially directs adipose stem cell differentiation towards osteogenic or chondrogenic lineages

Graphical abstract

Use of Lipotransfer in Scleroderma

Lipotransfer for soft tissue filling is a well-established plastic and aesthetic surgical technique. Elective fat grafting is considered a safe and well-tolerated procedure. Coleman and others have reported that fat grafting may have tissue regenerative properties and not only serve as a soft tissue filler. There have been reports from our group and others that it may improve fibrosis secondary to many different pathological aetiologies including scleroderma, burn injury, lichen sclerosis, graft vs host disease, and radiation. The mechanism of action remains unclear but has been postulated that is adipose derived stem cells (ADSCs) related. Lipoaspirate has been characterised and shown to contain several cell populations including fibroblasts, endothelial cells, and ADSCs. The ADSCs have shown to secrete angiogenic, immunodulatory, and antiapoptotic factors as well as proliferate and differentiate into different cell types similarly to other stem cell sources. We have shown that ADSCs are functionally different in scleroderma patients but despite this lipotransfer produces a significant reversal in the effects of fibrosis in these patients. The advantage of lipoaspirate containing a valuable source of regenerative properties, ease of access, isolation, and processing may serve a significant future role in the treatment of fibrotic conditions.

Animal models for bone tissue engineering and modelling disease

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. Summary: This Review describes the currently used animal models of critical-sized bone defects and the regenerative bone tissue engineering strategies used in these models, as well as the application of bone tissue engineering for the advancement of cancer xenograft models.

Long-term secondary care costs of endometrial cancer: A prospective cohort study nested within the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)

Background There is limited evidence on the costs of Endometrial Cancer (EC) by stage of disease. We estimated the long-term secondary care costs of EC according to stage at diagnosis in an English population-based cohort. Methods Women participating in UKCTOCS and diagnosed with EC following enrolment (2001–2005) and prior to 31st Dec 2009 were identified to have EC through multiple sources. Survival was calculated through data linkage to death registry. Costs estimates were derived from hospital records accessed from Hospital Episode Statistics (HES) with additional patient level covariates derived from case notes and patient questionnaires. Missing and censored data was imputed using Multiple Imputation. Regression analysis of cost and survival was undertaken. Results 491 of 641 women with EC were included. Five year total costs were strongly dependent on stage, ranging from £9,475 (diagnosis at stage IA/IB) to £26,080 (diagnosis at stage III). Stage, grade and BMI were the strongest predictors of costs. The majority of costs for stage I/II EC were incurred in the first six months after diagnosis while for stage III / IV considerable costs accrued after the first six months. Conclusions In addition to survival advantages, there are significant cost savings if patients with EC are detected earlier.