MRCSI, Royal College of Surgeons in Ireland, Surgery (2011)
The Role of Stem Cells in Aesthetic Surgery: Fact or Fiction?
PLASTIC AND RECONSTRUCTIVE SURGERY
2014; 134 (2): 193-200
Stem cells are attractive candidates for the development of novel therapies, targeting indications that involve functional restoration of defective tissue. Although most stem cell therapies are new and highly experimental, there are clinics around the world that exploit vulnerable patients with the hope of offering supposed stem cell therapies, many of which operate without credible scientific merit, oversight, or other patient protection.We review the potential, as well as drawbacks, for incorporation of stem cells in cosmetic procedures. A review of FDA-approved indications and ongoing clinical trials with adipose stem cells is provided. Furthermore, a "snapshot" analysis of websites using the search terms "stem cell therapy" or "stem cell treatment" or "stem cell facelift" was performed.Despite the protective net cast by regulatory agencies such as the FDA and professional societies such as the American Society of Plastic Surgeons, we are witnessing worrying advertisements for procedures such as stem cell facelifts, stem cell breast augmentations, and even stem cell vaginal rejuvenation. The marketing and promotion of stem cell procedures in aesthetic surgery is not adequately supported by clinical evidence in the majority of cases.Stem cells offer tremendous potential, but the marketplace is saturated with unsubstantiated and sometimes fraudulent claims that may place patients at risk. With plastic surgeons at the forefront of stem cell-based regenerative medicine, it is critically important that we provide an example of a rigorous approach to research, data collection, and advertising of stem cell therapies.
View details for DOI 10.1097/PRS.0000000000000404
View details for Web of Science ID 000339777300004
Studies in fat grafting: Part I. Effects of injection technique on in vitro fat viability and in vivo volume retention.
Plastic and reconstructive surgery
2014; 134 (1): 29-38
Fat grafting has become increasingly popular for the correction of soft tissue deficits at many sites throughout the body. Long-term outcomes, however, depend on delivery of fat in the least traumatic fashion to optimize viability of the transplanted tissue. In this study, we compare the biologic properties of fat following injection using two methods.Lipoaspiration samples were obtained from five female donors and cellular viability, proliferation, and lipolysis were evaluated following injection using either a modified Coleman technique or an automated, low shear device. Comparisons were made to minimally processed, uninjected fat. Volume retention was also measured over twelve weeks following injection of fat under the scalp of immunodeficient mice using either the modified Coleman technique or the Adipose Tissue Injector. Finally, fat grafts were analyzed histologically.Fat viability and cellular proliferation were both significantly greater with the Adipose Tissue Injector relative to injection with the modified Coleman technique. In contrast, significantly less lipolysis was noted using the automated device. In vivo fat volume retention was significantly greater than with the modified Coleman technique at 4, 6, 8, and 12 week time points. This corresponded with significantly greater histological scores for healthy fat and lower scores for injury following injection with the device.Biological properties of injected tissues reflect how disruptive and harmful techniques for placement of fat may be, and our in vitro and in vivo data both support the use of the automated, low shear devices compared to the modified Coleman technique.
View details for DOI 10.1097/PRS.0000000000000290
View details for PubMedID 24622574
Tissue Engineering and Regenerative Repair in Wound Healing
ANNALS OF BIOMEDICAL ENGINEERING
2014; 42 (7): 1494-1507
Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration.
View details for DOI 10.1007/s10439-014-1010-z
View details for Web of Science ID 000338995900013
- Studies in Fat Grafting: Part I. Effects of Injection Technique on In Vitro Fat Viability and In Vivo Volume Retention PLASTIC AND RECONSTRUCTIVE SURGERY 2014; 134 (1): 29-38
Gene expression in fetal murine keratinocytes and fibroblasts
JOURNAL OF SURGICAL RESEARCH
2014; 190 (1): 344-357
Early fetuses heal wounds without the formation of a scar. Many studies have attempted to explain this remarkable phenomenon. However, the exact mechanism remains unknown. Herein, we examine the predominant cell types of the epidermis and dermis-the keratinocyte and fibroblast-during different stages of fetal development to better understand the changes that lead to scarring wound repair versus regeneration.Keratinocytes and fibroblasts were harvested and cultured from the dorsal skin of time-dated BALB/c fetuses. Total RNA was isolated and microarray analysis was performed using chips with 42,000 genes. Significance analysis of microarrays was used to select genes with >2-fold expression differences with a false discovery rate <2. Enrichment analysis was performed on significant genes to identify differentially expressed pathways.By comparing the gene expression profile of keratinocytes from E16 versus E18 fetuses, we identified 24 genes that were downregulated at E16. Analysis of E16 and E18 fibroblasts revealed 522 differentially expressed genes. Enrichment analysis showed the top 20 signaling pathways that were downregulated in E16 keratinocytes and upregulated or downregulated in E16 fibroblasts.Our data reveal 546 differentially expressed genes in keratinocytes and fibroblasts between the scarless and scarring transition. In addition, a total of 60 signaling pathways have been identified to be either upregulated or downregulated in these cell types. The genes and pathways recognized by our study may prove to be essential targets that may discriminate between fetal wound regeneration and adult wound repair.
View details for DOI 10.1016/j.jss.2014.02.030
View details for Web of Science ID 000338444700051
View details for PubMedID 24726057
- Studies in Fat Grafting: Part II. Effects of Injection Mechanics on Material Properties of Fat PLASTIC AND RECONSTRUCTIVE SURGERY 2014; 134 (1): 39-46
Adipose-Derived Stem Cells: A Review of Signaling Networks Governing Cell Fate and Regenerative Potential in the Context of Craniofacial and Long Bone Skeletal Repair
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
2014; 15 (6): 9314-9330
Improvements in medical care, nutrition and social care are resulting in a commendable change in world population demographics with an ever increasing skew towards an aging population. As the proportion of the world's population that is considered elderly increases, so does the incidence of osteodegenerative disease and the resultant burden on healthcare. The increasing demand coupled with the limitations of contemporary approaches, have provided the impetus to develop novel tissue regeneration therapies. The use of stem cells, with their potential for self-renewal and differentiation, is one potential solution. Adipose-derived stem cells (ASCs), which are relatively easy to harvest and readily available have emerged as an ideal candidate. In this review, we explore the potential for ASCs to provide tangible therapies for craniofacial and long bone skeletal defects, outline key signaling pathways that direct these cells and describe how the developmental signaling program may provide clues on how to guide these cells in vivo. This review also provides an overview of the importance of establishing an osteogenic microniche using appropriately customized scaffolds and delineates some of the key challenges that still need to be overcome for adult stem cell skeletal regenerative therapy to become a clinical reality.
View details for DOI 10.3390/ijms15069314
View details for Web of Science ID 000338639000009
Induced Pluripotent Stem Cells in Regenerative Medicine and Disease Modeling
CURRENT STEM CELL RESEARCH & THERAPY
2014; 9 (2): 73-81
In 2006, Dr. Yamanaka created the induced pluripotent stem cell (iPSC) by reprogramming adult fibroblasts back to an immature, pluripotent state. Effectively bypassing the ethical constraints of human embryonic stem cells, iPSCs have expanded the horizons of regenerative medicine by offering a means to derive autologous patient-matched cells and tissues for clinical transplantation. However, persisting safety concerns must be addressed prior to their widespread clinical application. In this review, we discuss the history of iPSCs, derivation strategies, and current research involving gene therapy and disease modeling. We review the potential of iPSCs for improving a range of cell-based therapies and obstacles to their clinical implementation.
View details for Web of Science ID 000331890000001
View details for PubMedID 24359141
- Cell Intrinsic versus Extrinsic Factors and their Role in Skeletal Stem Cell Function with Aging. Journal of Surgical Research 2014
- Blood-Derived Mesenchymal Stem Cells Heal Calvarial Defects Journal of Surgical Research 2014; 186 (2)
- Gene Expression in Fetal Skin Development and Wounds. Journal of Surgical Research 2014; 186 (2)
- Analysis of Gene Expression in Fetal Keratinocytes and Fibroblasts. Journal of Surgical Research 2014; 186 (2)
The Role of Stem Cells During Scarless Skin Wound Healing.
Advances in Wound Care
View details for DOI 10.1089/wound.2013.0471.
- Comparison of Therapeutic Adipose-Derived Stem Cell Delivery Methods for the Treatment of Cutaneous Wounds. Journal of Surgical Research 2014; 186 (2)
Isolation of Human Adipose-Derived Stromal Cells Using Laser-Assisted Liposuction and Their Therapeutic Potential in Regenerative Medicine
STEM CELLS TRANSLATIONAL MEDICINE
2013; 2 (10): 808-817
Harvesting adipose-derived stromal cells (ASCs) for tissue engineering is frequently done through liposuction. However, several different techniques exist. Although third-generation ultrasound-assisted liposuction has been shown to not have a negative effect on ASCs, the impact of laser-assisted liposuction on the quality and differentiation potential of ASCs has not been studied. Therefore, ASCs were harvested from laser-assisted lipoaspirate and suction-assisted lipoaspirate. Next, in vitro parameters of cell yield, cell viability and proliferation, surface marker phenotype, osteogenic differentiation, and adipogenic differentiation were performed. Finally, in vivo bone formation was assessed using a critical-sized cranial defect in athymic nude mice. Although ASCs isolated from suction-assisted lipoaspirate and laser-assisted lipoaspirate both successfully underwent osteogenic and adipogenic differentiation, the cell yield, viability, proliferation, and frequency of ASCs (CD34(+)CD31(-)CD45(-)) in the stromal vascular fraction were all significantly less with laser-assisted liposuction in vitro (p < .05). In vivo, quantification of osseous healing by micro-computed tomography revealed significantly more healing with ASCs isolated from suction-assisted lipoaspirate relative to laser-assisted lipoaspirate at the 4-, 6-, and 8-week time points (p < .05). Therefore, as laser-assisted liposuction appears to negatively impact the biology of ASCs, cell harvest using suction-assisted liposuction is preferable for tissue-engineering purposes.
View details for DOI 10.5966/sctm.2012-0183
View details for Web of Science ID 000325384600015
- Commentary on the differential healing capacity of calvarial bone. journal of craniofacial surgery 2013; 24 (2): 344-345
- Discussion: A report of the ASPS Task Force on regenerative medicine: opportunities for plastic surgery. Plastic and reconstructive surgery 2013; 131 (2): 400-403
- In vivo tumor inhibition by full thickness wounds. Journal of the American College of Surgeons 2013
- Manipulation of Stem Cells and their Microenvironment for Tissue Engineering. Surgery: Current Research 2013; 3 (134)
Vaginal Reconstruction Following Radical Surgery for Colorectal Malignancies: A Systematic Review of the Literature
ANNALS OF SURGICAL ONCOLOGY
2012; 19 (12): 3933-3942
Vaginectomy is frequently indicated to ensure an adequate resection in rectal cancer. This paper reviews the success, complications, and functional results after various methods of vaginal reconstruction following resection for rectal tumors.A systematic review of the literature was performed by using the MEDLINE database, Embase, and the Cochrane library (1990-2010).Eighteen papers were available to review. Fifty percent of all women who received a neovagina following vaginectomy returned to sexual activity postoperatively. The rectus abdominis myocutaneous (RAM) flap remains the most common method of vaginal reconstruction after surgery for colorectal cancer. Advantages include low operative morbidity, a wide arc of rotation, and ease of harvest. Alternatives to flap reconstruction of the vagina have limited indications because of higher morbidity rates.Preferred techniques for vaginal reconstruction following vaginectomy with colorectal cancer resection include RAM flaps for partial posterior vaginal defects and bilateral Gracilis myocutaneous flaps for complete vaginal excisions.
View details for DOI 10.1245/s10434-012-2503-3
View details for Web of Science ID 000310225700043
View details for PubMedID 23010729
- Craniosynostosis Molecular pathways and future pharmacologic therapy ORGANOGENESIS 2012; 8 (4): 103-113
Preferences for the White Female Nasal Supratip Break
ANNALS OF PLASTIC SURGERY
2012; 68 (4): 366-368
The debate on how to create ideal facial proportions--once the remit of artists and sculptors--has been reignited during the past 5 decades, with the emergence of aesthetic facial surgery. Classic ideals exist, but few individuals actually satisfy these criteria. Aesthetic ideals are culturally and temporally variable. For centuries, the optimum nasal profile, particularly the supratip break (STB), has long been a matter for debate. Little is published on preferences for the STB. We therefore undertook a population study to determine the preferred angulation of the STB.Lateral profile photographs of 10 models were taken under standard conditions in forward gaze. The angulation of the STB was altered in one of the photographs of each model, so that one photograph had a subtle angulation of the STB and the other had a more marked angulation. Participants in the study were shown 2 photographs of each of the 10 models. One hundred male and female participants were recruited to the study and asked to indicate their preference for the nasal tip for each of the models. Statistical analysis was performed using the Wilcoxon signed-rank test to determine significance.Both male and female participants in the study indicated an overall, and statistically significant, preference for lateral profile photographs showing a nasal tip with a very subtle angulation of the STB, compared with a larger angulation of the STB.This study provides strong evidence that a subtle STB in the white female subject is most favorable.
View details for DOI 10.1097/SAP.0b013e31823f3ca1
View details for Web of Science ID 000301800600009
View details for PubMedID 22421480
Craniosynostosis: Molecular pathways and future pharmacologic therapy.
2012; 8 (4)
Craniosynostosis describes the premature fusion of one or more cranial sutures and can lead to dramatic manifestations in terms of appearance and functional impairment. Contemporary approaches for this condition are primarily surgical and are associated with considerable morbidity and mortality. The additional post-operative problems of suture refusion and bony relapse may also necessitate repeated surgeries with their own attendant risks. Therefore, a need exists to not only optimize current strategies but also to develop novel biological therapies which could obviate the need for surgery and potentially treat or even prevent premature suture fusion. Clinical studies of patients with syndromic craniosynostosis have provided some useful insights into the important signaling pathways and molecular events guiding suture fate. Furthermore, the highly conserved nature of craniofacial development between humans and other species have permitted more focused and step-wise elucidation of the molecular underpinnings of craniosynostosis. This review will describe the clinical manifestations of craniosynostosis, reflect on our understanding of syndromic and non-syndromic craniosynostoses and outline the different approaches that have been adopted in our laboratory and elsewhere to better understand the pathogenesis of premature suture fusion. Finally, we will assess to what extent our improved understanding of the pathogenesis of craniosynostosis, achieved through laboratory-based and clinical studies, have made the possibility of a non-surgical pharmacological approach both realistic and tangible.
View details for PubMedID 23249483
- Duodenal duplication cyst presenting with gastric outlet obstruction in an adult male ENDOSCOPY 2011; 43: E352-E353
Partial herniation through the peritoneal defect of a pfannenstiel incision: a rare complication of non-closure.
Journal of obstetrics and gynaecology Canada : JOGC = Journal d'obstétrique et gynécologie du Canada : JOGC
2011; 33 (6): 625-627
The Pfannenstiel incision is used almost invariably in Caesarean section. With Caesarean section rates increasing, the Pfannenstiel is a commonly performed incision. The prevailing recommendation is not to close the peritoneum when closing a Pfannenstiel incision, and peritoneal non-closure does not appear to statistically influence postoperative complication rates.A 33-year-old woman presented with severe, intermittent lower abdominal pain one year after a Caesarean section. Laparoscopy showed a hernial defect at the Pfannenstiel incision, between the left rectus abdominis muscle and the anterior rectus sheath. Mesh repair was performed with uncomplicated postoperative outcome.The current case illustrates that complications specific to non-closure of the peritoneum do arise. We advocate that laparoscopy should be considered for any patient with persistent, severe, or atypical pain following a Pfannenstiel incision.
View details for PubMedID 21846453
- Large-bowel obstruction secondary to urinary retention COLORECTAL DISEASE 2011; 13 (6): E160-E161
Osteopoikilosis masquerading as osseous metastases in breast cancer.
Breast cancer (Tokyo, Japan)
Osteopoikilosis (OPK) is a rare, congenital bone disorder characterised by multiple round or ovoid radio densities appearing throughout the axial and appendicular skeleton. It is usually an asymptomatic condition diagnosed incidentally on radiological imaging, and may mimic other bone disorders, including osseous metastases. In this case report, we present a patient with lobular breast cancer whose computed tomography findings were thought to be consistent with osseous cancer metastases. Radionuclide bone scintigraphy plays a key role in distinguishing OPK from osteoblastic bone metastases. This case demonstrates the importance of a clinical awareness of OPK to ensure that patients with potentially curable disease are properly diagnosed.
View details for PubMedID 21990037
A case of "refractory" lupus erythematosus profundus responsive to rituximab [case report]
2009; 28 (6): 745-746
Lupus erythematosus profundus is a rare complication of systemic lupus erythematosus characterized by the presence of deep, tender subcutaneous nodules. A 22-year-old African-American female with extensive lupus profundus resistant to conventional therapies was treated with two infusions of the anti-CD20 monoclonal antibody, rituximab, at a dosage of 1,000 mg each. The patient demonstrated a remarkable clinical response as indicated by the disappearance of the nodules. B-cell depletion therapy with rituximab used alone or in combination with other therapies may be a viable option in patients with lupus profundus refractory to current therapies.
View details for DOI 10.1007/s10067-009-1158-3
View details for Web of Science ID 000265831800022
View details for PubMedID 19343472