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1.
JPRAS Open ; 41: 116-127, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38984322

ABSTRACT

Introduction: Enhanced recovery after surgery (ERAS) protocols have been implemented to decrease opioid use and decrease patient hospital length of stay (LOS, days). Serratus anterior plane (SAP) blocks anesthetize the T2 through T9 dermatomes of the breast and can be applied intraoperatively. The purpose of this study was to compare postoperative opioid (OME) consumption and LOS between a control group, an ERAS group, and an ERAS/local anesthetic cocktail group in patients who underwent implant-based breast reconstruction. Methods: In this study, 142 women who underwent implant-based breast reconstruction between 2004 and 2020 were divided into Group A (46 patients), a historical cohort; Group B (73 patients), an ERAS/no-block control group; and Group C (23 patients), an ERAS/anesthetic cocktail study group. Primary outcomes of interest were postanesthesia care unit (PACU), inpatient and total hospital OME consumption, and PACU LOS. Results: A significant decrease was observed from Group A to C in PACU LOS (103.3 vs. 80.2 vs. 70.5; p = 0.011), OME use (25.1 vs. 11.4 vs. 5.7; p < 0.0001), and total hospital OME (120.3 vs. 95.2 vs. 35.9; p < 0.05). No difference was observed in inpatient OMEs between the three groups (95.2 vs. 83.8 vs. 30.8; p = 0.212). Despite not reaching statistical significance, Group C consumed an average of 50-60 % less opioids per patient than did Group B in PACU, inpatient, and total hospital OMEs. Conclusion: Local anesthetic blocks are important components of ERAS protocols. Our results demonstrate that a combination regional block with a local anesthetic cocktail in an ERAS protocol can decrease opioid consumption in implant-based breast reconstruction.

2.
Plast Reconstr Surg ; 153(3): 650e-655e, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-37220273

ABSTRACT

BACKGROUND: Microsurgery is conducted on tiny anatomical structures such as blood vessels and nerves. Over the past few decades, little has changed in the way plastic surgeons visualize and interact with the microsurgical field. New advances in augmented reality (AR) technology present a novel method for microsurgical field visualization. Voice- and gesture-based commands can be used in real time to adjust the size and position of a digital screen. Surgical decision support and/or navigation may also be used. The authors assess the use of AR in microsurgery. METHODS: The video feed from a Leica Microsystems OHX surgical microscope was streamed to a Microsoft HoloLens2 AR headset. A fellowship-trained microsurgeon and three plastic surgery residents then performed a series of four arterial anastomoses on a chicken thigh model using the AR headset, a surgical microscope, a video microscope (or "exoscope"), and surgical loupes. RESULTS: The AR headset provided an unhindered view of the microsurgical field and peripheral environment. The subjects remarked on the benefits of having the virtual screen track with head movements. The ability of participants to place the microsurgical field in a tailored comfortable, ergonomic position was also noted. Points of improvement were the low image quality compared with current monitors, image latency, and the lack of depth perception. CONCLUSIONS: AR is a useful tool that has the potential to improve microsurgical field visualization and the way surgeons interact with surgical monitors. Improvements in screen resolution, latency, and depth of field are needed.


Subject(s)
Augmented Reality , Plastic Surgery Procedures , Surgery, Plastic , Humans , Microsurgery/methods , Neurosurgical Procedures/methods
3.
Proc (Bayl Univ Med Cent) ; 36(4): 501-509, 2023.
Article in English | MEDLINE | ID: mdl-37334077

ABSTRACT

Introduction: Perioperative pain control is an important component of any plastic surgery practice. Due to the incorporation of Enhanced Recovery after Surgery (ERAS) protocols, reported pain level, opioid consumption, and hospital length of stay numbers have decreased significantly. This article provides an up-to-date review of current ERAS protocols in use, reviews individual aspects of ERAS protocols, and discusses future directions for the continual improvement of ERAS protocols and control of postoperative pain. ERAS components: ERAS protocols have proven to be excellent methods of decreasing patient pain, opioid consumption, and postanesthesia care unit (PACU) and/or inpatient length of stay. ERAS protocols have three phases: preoperative education and pre-habilitation, intraoperative anesthetic blocks, and a postoperative multimodal analgesia regimen. Intraoperative blocks consist of local anesthetic field blocks and a variety of regional blocks, with lidocaine or lidocaine cocktails. Various studies throughout the surgical literature have demonstrated the efficacy of these aspects and their relevance to the overall goal of decreasing patient pain, both in plastic surgery and other surgical fields. In addition to the individual ERAS phases, ERAS protocols have shown promise in both the inpatient and outpatient sectors of plastic surgery of the breast. Conclusion: ERAS protocols have repeatedly been shown to provide improved patient pain control, decreased hospital or PACU length of stay, decreased opioid use, and cost savings. Although protocols have most commonly been utilized in inpatient plastic surgery procedures of the breast, emerging evidence points towards similar efficacy when used in outpatient procedures. Furthermore, this review demonstrates the efficacy of local anesthetic blocks in controlling patient pain.

4.
Plast Reconstr Surg ; 151(4): 727-735, 2023 04 01.
Article in English | MEDLINE | ID: mdl-36729992

ABSTRACT

BACKGROUND: The authors seek to evaluate the impact of age, body mass index (BMI), and resection weight, on postoperative complications in women undergoing primary bilateral reduction mammaplasty. METHODS: A retrospective review of all primary bilateral reduction mammaplasties between February of 2014 and August of 2018 was performed. Patient demographics, medical comorbidities, tobacco use, BMI, operative technique, operative time, resection weight, and complications were reviewed. RESULTS: Two hundred seventy-seven women were included. Mean age was 35.71 years, and BMI was 30.17 kg/m 2 . An inferior pedicle (53.07%) with Wise pattern resection (53.43%) was used most commonly. The minor complication rate was 49.1%, with superficial wounds (42.1%) occurring most commonly. Thirty-three women (11.9%) required greater than 2 months to heal. The major complication rate was 4.31%. BMI was not associated with minor or major complications on univariate analysis ( P = 0.1003 and P = 0.6163), but was associated with wound healing requiring greater than 2 months ( P = 0.0009), longer operative times ( P = 0.0002), and higher resection weights ( P < 0.00001). Greater age was associated with higher minor complication rates ( P = 0.0048). On multivariate analysis, BMI was associated with wound healing requiring greater than 2 months ( P = 0.0137), and age with minor complications ( P = 0.0180). No factors impacted major complication rates. CONCLUSIONS: Women with higher BMI are more likely to require larger resections, longer operative times, and are at higher risk for wound healing requiring greater than 2 months. Although BMI is an important consideration for determining operative candidacy, the benefits of reduction may outweigh these risks in carefully selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Subject(s)
Mammaplasty , Postoperative Complications , Humans , Female , Adult , Body Mass Index , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Mammaplasty/adverse effects , Mammaplasty/methods , Retrospective Studies , Comorbidity
5.
Proc (Bayl Univ Med Cent) ; 34(2): 269-273, 2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33678960

ABSTRACT

The COVID-19 pandemic has presented new challenges to microsurgeons. The virus is highly transmissible, with increased risk during operations that involve the aerodigestive tract. It is important to be able to identify high-risk operations and scenarios to guide management decisions and selection of personal protective equipment. Preoperative testing is a key element in identifying high-risk scenarios, and preoperative testing protocols are essential to maintaining safety in the COVID-19 era. Because COVID-19 can be transmitted via the conjunctiva, adaptations to loupes and microscopes are necessary to safely perform microsurgery in high-risk scenarios. We outline a potential risk stratification algorithm, as well as precautions for each scenario. Potential areas for innovation are also discussed.

6.
J Plast Reconstr Aesthet Surg ; 74(3): 475-479, 2021 03.
Article in English | MEDLINE | ID: mdl-32972878

ABSTRACT

BACKGROUND: Enhanced recovery after surgery (ERAS) is increasingly used in plastic surgery to optimize patient care. Mitigating the risk of postoperative complications is particularly important in patients with risk factors, such as obesity. The objective of this study is to evaluate the impact of the ERAS pathway in patients, stratified by BMI, undergoing free flap breast reconstruction on length of stay and complications. METHODS: A retrospective review of all patients who underwent abdominally based free flap breast reconstruction from January 2014 to December 2017 was performed. Data collected include participation in the ERAS protocol, patient demographics, length of stay (LOS), complications (minor and major), and 30-day reoperation rates. RESULTS: A total of 123 patients met the inclusion criteria, with 36 non-ERAS and 87 ERAS patients. ERAS patients had a shorter length of stay than non-ERAS patients (4.14 vs. 4.69, p = 0.049). Higher BMI patients progressively benefited from their involvement in an ERAS pathway: class I obese patients had an LOS decrease of 0.99 days (p = 0.048) and class II+ obese patients had an LOS decrease of 1.35 days (p = 0.093). Minor complications, major complications, and reoperation rates were similar between ERAS and non-ERAS patients (p>0.05). CONCLUSION: Utilization of an ERAS protocol for free flap breast reconstruction safely decreases LOS, especially with increasing BMI. Patients benefit from an ERAS protocol without increasing risk of postoperative complications, compared to non-ERAS patients of similar BMIs.


Subject(s)
Enhanced Recovery After Surgery/standards , Free Tissue Flaps , Mammaplasty , Obesity , Postoperative Complications , Reoperation , Adult , Body Mass Index , Clinical Protocols , Female , Free Tissue Flaps/adverse effects , Free Tissue Flaps/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Mammaplasty/adverse effects , Mammaplasty/methods , Mammaplasty/rehabilitation , Middle Aged , Obesity/diagnosis , Obesity/surgery , Outcome and Process Assessment, Health Care , Patient Acceptance of Health Care , Postoperative Complications/etiology , Postoperative Complications/surgery , Reoperation/methods , Reoperation/statistics & numerical data , Retrospective Studies
7.
Plast Reconstr Surg Glob Open ; 8(11): e3258, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33299720

ABSTRACT

The COVID-19 pandemic has had significant implications for citizens globally and for the healthcare system, including plastic surgeons. Operations of the upper aerodigestive tract, including head and neck reconstruction and craniomaxillofacial procedures, are of particularly high risk because they may aerosolize the virus and lead to severe surgeon and surgical team illness. Until the virus is eradicated or widespread vaccination occurs, we recommend certain precautions to safely perform these operations. We propose evolving algorithms for head and neck reconstruction and facial trauma surgeries to maintain provider safety. Central to these guidelines are preoperative COVID-19 testing, appropriate personal protective equipment, and operative techniques/principles that minimize operative time and aerosolization of the virus. We aim to provide efficient care to our patients throughout this pandemic, while maintaining the safety of plastic surgeons and other healthcare providers.

8.
Plast Reconstr Surg Glob Open ; 8(3): e2668, 2020 Mar.
Article in English | MEDLINE | ID: mdl-32537332

ABSTRACT

Immediate fat grafting to the pedicled myocutaneous latissimus dorsi (LD) flap has recently gained in popularity as a means to supplement volume for breast reconstruction. The aim of this study is to compare complication rates of the immediately fat-grafted LD to free tissue transfer in the obese population. METHODS: In this retrospective cohort, 82 patients (149 breasts) from 2015 to 2019 were included. Patients underwent either unilateral or bilateral breast reconstruction with either LD with immediate fat grafting or abdominal-based free tissue transfer. Included patients had a body mass index ≥ 30 kg/m2 at the time of surgery. Complication data were recorded as minor, major, and medical complications. Procedure characteristics and postoperative data were also studied. RESULTS: Minor complication rates between the LD with immediate fat grafting and free tissue transfer cases were similar (26.9% versus 26%, respectively). The free tissue transfer group had a significantly higher rate of major complications (20.3% versus 3.8%; P = 0.048) and medical complications (10.6% versus zero). Finally, the LD with immediate fat grafting group had significantly shorter operating room times, hospital length of stay, and fewer donor-site revisions. CONCLUSIONS: LD with immediate fat grafting offers the benefit of a totally autologous reconstruction without the risks of abdominal-based microvascular free tissue transfer or an implant. Favorable complication rates, shorter operative times, and shorter hospital length of stay make this reconstructive option a safe alternative to free tissue transfer in the obese population.

9.
Plast Reconstr Surg ; 133(1): 39e-48e, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24374686

ABSTRACT

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Discuss the approach and rationale of pressure sore management, including specific techniques of bone biopsy and postoperative care resulting in a significant reduction in recurrence rates. 2. Develop a surgical plan for reconstructing defects of the perineum, taking into account the local tissue factors and the soft-tissue requirements for reconstruction. SUMMARY: As close as the buttocks and the perineum are anatomically, the clinical settings and the solutions to wound problems in these areas are quite different. The ubiquitous "pressure ulcer" presents more commonly as a clinical management problem than a reconstruction issue. On the other hand, the perineal defect is almost always a reconstruction challenge following tumor ablation. For these reasons, the authors have chosen to separate this Continuing Medical Education offering into two parts. The first part addresses the pressure ulcer, while the latter discusses the perineum.


Subject(s)
Osteomyelitis/surgery , Perineum/surgery , Plastic Surgery Procedures/methods , Pressure Ulcer/surgery , Bed Rest , Buttocks/surgery , Education, Medical, Continuing , Groin/surgery , Humans , Nutritional Status , Osteomyelitis/diagnosis , Pelvis/surgery , Perforator Flap , Postoperative Care , Postoperative Complications/prevention & control , Pressure Ulcer/diagnosis , Surgical Flaps
10.
Plast Reconstr Surg ; 127(4): 1467-1477, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21460655

ABSTRACT

BACKGROUND: It is unclear whether mesenchymal stem cells that are applied to regenerate wound tissues can migrate to existing tumors and enhance their growth. The authors investigated whether adipose-derived stem cells had any effect on the growth and progression of distant tumors when applied to a skin wound. METHODS: The authors subcutaneously injected murine 4T1 breast cancer cells into all BALB/c-nu/nu mice. After tumor injection, mice were randomized to five groups (five mice per group) based on the means of co-introduction of green fluorescent protein-labeled adipose-derived stem cells, if any. In group 1, adipose-derived stem cells were combined and co-injected subcutaneously. In group 2, they were injected subcutaneously at a distant anatomical site. In group 3, they were injected intravenously. In group 4, they were delivered via a human acellular dermal matrix to a distant skin wound. In group 5, no adipose-derived stem cells were introduced. RESULTS: After 2 weeks, tumor volume increased in group 1 (356.5 ± 44.4 mm(3)), followed by group 3 (256.6 ± 47.1 mm(3)) and then group 2 (201.6 ± 28.6 mm(3)). In group 4, in which adipose-derived stem cells carried on acellular dermal matrix were applied to a wound distant to the primary tumor, the tumor volume was 143.8 ± 50.9 mm(3), which was similar to that observed in the control group (group 5; 167.8 ± 29.9 mm(3)). CONCLUSIONS: The authors' findings suggest that the wound microenvironment can retain adipose-derived stem cells, preventing their homing and stromal contribution to a distant neoplastic focus. These findings are an important first step in establishing the feasibility and safety of utilizing adipose-derived stem cell therapy for reconstructive surgery in the setting of malignancy.


Subject(s)
Adipose Tissue/cytology , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells/physiology , Neoplasms, Experimental/physiopathology , Skin/injuries , Wound Healing/physiology , Adult , Animals , Biocompatible Materials , Collagen , Genetic Vectors , Green Fluorescent Proteins , Humans , Immunohistochemistry , Injections, Intravenous , Injections, Subcutaneous , Lentivirus , Mice , Mice, Nude , Microradiography , Necrosis , Neoplasm Transplantation , Neoplasms, Experimental/diagnostic imaging , Neoplasms, Experimental/pathology , Transfection
11.
Plast Reconstr Surg ; 126(3): 845-854, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20463622

ABSTRACT

BACKGROUND: Bioprosthetic mesh used for ventral hernia repair becomes incorporated into the musculofascial edge by cellular infiltration and vascularization. Adipose tissue-derived stem cells promote tissue repair and vascularization and may increase the rate or degree of tissue incorporation. The authors hypothesized that introducing these cells into bioprosthetic mesh would result in adipose tissue-derived stem cell engraftment and proliferation and enhance incorporation of the bioprosthetic mesh. METHODS: Adipose tissue-derived stem cells were isolated from the subcutaneous adipose tissue of syngeneic Brown Norway rats, expanded in vitro, and labeled with green fluorescent protein. Thirty-six additional rats underwent inlay ventral hernia repair with porcine acellular dermal matrix. Two 12-rat groups had the cells (1.0 x 10(6)) injected directly into the musculofascial/porcine acellular dermal matrix interface after repair or received porcine acellular dermal matrix on which the cells had been preseeded; the 12-rat control group received no stem cells. RESULTS: At 2 weeks, adipose tissue-derived stem cells in both stem cell groups engrafted, survived, migrated, and proliferated. Mean cellular infiltration into porcine acellular dermal matrix at the musculofascial/graft interface was significantly greater in the preseeded and injected stem cell groups than in the control group. Mean vascular infiltration of the porcine acellular dermal matrix was significantly greater in both stem cell groups than in the control group. CONCLUSIONS: Preseeded and injected adipose tissue-derived stem cells engraft, migrate, proliferate, and enhance the vascularity of porcine acellular dermal matrix grafts at the musculofascial/graft interface. These cells can thus enhance incorporation of porcine acellular dermal matrix into the abdominal wall after repair of ventral hernias.


Subject(s)
Adipose Tissue/cytology , Bioprosthesis , Hernia, Ventral/surgery , Stem Cell Transplantation , Stem Cells , Surgical Mesh , Animals , Combined Modality Therapy , Rats
12.
J Biomed Mater Res A ; 94(2): 515-23, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20186770

ABSTRACT

Regenerative tissue engineering requires biomaterials that would mimic structure and composition of the extracellular matrix to facilitate cell infiltration, differentiation, and vascularization. Engineered scaffolds composed of natural biomaterials silk fibroin (SF) and chitosan (CS) blend were fabricated to achieve fibrillar nano-structures aligned in three-dimensions using the technique of dielectrophoresis. The effect of scaffold properties on adhesion and migration of human adipose-derived stem cells (hASC) and endothelial cells (HUVEC) was studied on SFCS (micro-structure, unaligned) and engineered SFCS (E-SFCS; nano-structure, aligned). E-SFCS constituted of a nano-featured fibrillar sheets, whereas SFCS sheets had a smooth morphology with unaligned micro-fibrillar extensions at the ends. Adhesion of hASC to either scaffolds occurred within 30 min and was higher than HUVEC adhesion. The percentage of moving cells and average speed was highest for hASC on SFCS scaffold as compared to hASC cocultured with HUVEC. HUVEC interactions with hASC appeared to slow the speed of hASC migration (in coculture) on both scaffolds. It is concluded that the guidance of cells for regenerative tissue engineering using SFCS scaffolds requires a fine balance between cell-cell interactions that affect the migration speed of cells and the surface characteristics that affects the overall adhesion and direction of migration.


Subject(s)
Chitosan/chemistry , Endothelial Cells/metabolism , Fibroins/chemistry , Silk/chemistry , Stem Cells/metabolism , Tissue Scaffolds/chemistry , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Cell Adhesion , Cell Movement , Cells, Cultured , Chitosan/metabolism , Coculture Techniques , Endothelial Cells/cytology , Fibroins/metabolism , Humans , Materials Testing , Microscopy , Regeneration/physiology , Silk/metabolism , Stem Cells/cytology
13.
Plast Reconstr Surg ; 125(1): 63-73, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20048601

ABSTRACT

BACKGROUND: Transplantation of adipose tissue-resident mesenchymal stem cells has been found to contribute to the establishment of a supportive fibrovascular network. The authors sought to evaluate the potential of human adipose tissue-derived stem cells to integrate with nonanimal stabilized hyaluronic acid as a novel injectable soft-tissue filler. METHODS: Cell proliferation was measured by bromodeoxyuridine incorporation. Interactions of adipose tissue-derived stem cells with hyaluronic acid were documented by scanning electron microscopy. The effect of this combination on procollagen mRNA was assessed by real-time polymerase chain reaction. The potential therapeutic effects were evaluated in an athymic murine photoaged skin model by histology and by high-resolution magnetic resonance imaging. Angiogenesis was assessed by microvessel density analysis. RESULTS: Under in vitro culture conditions, the authors found an equal proliferation capacity of adipose tissue-derived stem cells grown on hyaluronic acid versus controls. Scanning electron microscopy showed enhanced establishment of complex microvillous networks in adipose tissue-derived stem cells adherent to hyaluronic acid compared with controls. Adipose tissue-derived stem cells and hyaluronic acid induced a significant increase in procollagen 1-alpha-2 mRNA expression compared with controls. In an athymic murine photoaged skin model, injection of this combination ablated photoinduced skin wrinkles. Magnetic resonance imaging revealed a consistent and stable volume fill by adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid at 3 weeks. Adipose tissue-derived stem cells actively incorporated into the hyaluronic acid fill and showed an organized fibrovascular network at 3 weeks. CONCLUSION: The combination of adipose tissue-derived stem cells and nonanimal stabilized hyaluronic acid holds promise as a tool with which to achieve lasting volume fill in reconstructive surgical soft-tissue augmentation.


Subject(s)
Adipose Tissue/cytology , Skin Aging , Animals , Cell Proliferation , Green Fluorescent Proteins , Humans , Hyaluronic Acid , Immunohistochemistry , Magnetic Resonance Imaging , Mice , Mice, Nude , Microscopy, Electron, Scanning , Microvilli , Neovascularization, Physiologic , Skin/pathology , Soft Tissue Injuries , Stem Cells/cytology , Stromal Cells , Tissue Scaffolds
14.
Acta Biomater ; 6(4): 1388-97, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19861180

ABSTRACT

Silk fibroin-chitosan (SFCS) scaffold is a naturally derived biocompatible matrix with potential reconstructive surgical applications. In this study, human adipose-derived mesenchymal stem cells (ASCs) were seeded on SFCS scaffolds and cell attachment was characterized by fluorescence, confocal, time-lapse, atomic force, and scanning electron microscopy (SEM) studies. Adhesion of ASCs on SFCS was 39.4 + or - 4.8% at 15 min, increasing to 92.8+/-1.5% at 120 min. ASC adhered at regions of architectural complexity and infiltrate into three-dimensional scaffold. Time-lapse confocal studies indicated a mean ASC speed on SFCS of 18.47+/-2.7 microm h(-1) and a mean persistence time of 41.4 + or - 9.3 min over a 2.75 h study period. Cytokinetic and SEM studies demonstrated ASC-ASC interaction via microvillus extensions. The apparent elastic modulus was significantly higher (p<0.0001) for ASCs seeded on SFCS (69.0 + or - 9.0 kPa) than on glass (6.1 + or - 0.4 kPa). Also, cytoskeleton F-actin fiber density was higher (p<0.05) for ASC seeded on SFCS (0.42 + or - 0.02 fibers microm(-1)) than on glass-seeded controls (0.24 + or - 0.03 fibers microm(-1)). Hence, SFCS scaffold facilitates mesenchymal stem cell attachment, migration, three-dimensional infiltration, and cell-cell interaction. This study showed the potential use of SFCS as a local carrier for autologous stem cells for reconstructive surgery application.


Subject(s)
Adipose Tissue/cytology , Cell Movement/drug effects , Chitosan/pharmacology , Fibroins/pharmacology , Silk/pharmacology , Stem Cells/cytology , Stem Cells/drug effects , Actins/metabolism , Adult , Biomechanical Phenomena/drug effects , Cell Adhesion/drug effects , Elastic Modulus/drug effects , Green Fluorescent Proteins/metabolism , Humans , Microscopy, Fluorescence , Stem Cells/ultrastructure , Time Factors , Tissue Scaffolds
15.
Carcinogenesis ; 30(4): 589-97, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19181699

ABSTRACT

Mesenchymal stem cells derived from bone marrow have recently been described to localize to breast carcinomas and to integrate into the tumor-associated stroma. In the present study, we investigated whether adipose tissue-derived stem cells (ASCs) could play a role in tumor growth and invasion. Compared with bone marrow-derived cells, ASCs as tissue-resident stem cells are locally adjacent to breast cancer cells and may interact with tumor cells directly. Here, we demonstrate that ASCs cause the cancer to grow significantly faster when added to a murine breast cancer 4T1 cell line. We further show that breast cancer cells enhance the secretion of stromal cell-derived factor-1 from ASCs, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. The tumor-promoting effect of ASCs was abolished by knockdown of the chemokine C-X-C receptor 4 in 4T1 tumor cells. We demonstrated that ASCs home to tumor site and promote tumor growth not only when co-injected locally but also when injected intravenously. Furthermore, we demonstrated that ASCs incorporate into tumor vessels and differentiate into endothelial cells. The tumor-promoting effect of tissue-resident stem cells was also tested and validated using a human breast cancer line MDA-MB-231 cells and human adipose tissue-derived stem cells. Our findings indicate that the interaction of local tissue-resident stem cells with tumor stem cells plays an important role in tumor growth and metastasis.


Subject(s)
Lung Neoplasms/secondary , Mammary Neoplasms, Animal/pathology , Neoplastic Stem Cells/metabolism , Adipose Tissue/metabolism , Adipose Tissue/pathology , Animals , Blotting, Western , Cell Movement , Chemokine CXCL12/metabolism , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunoprecipitation , Lung Neoplasms/metabolism , Male , Mammary Neoplasms, Animal/metabolism , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Neovascularization, Pathologic , Receptors, CXCR4/antagonists & inhibitors , Receptors, CXCR4/genetics , Receptors, CXCR4/metabolism , Spheroids, Cellular , Stromal Cells/cytology , Stromal Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism
16.
Stem Cells ; 27(1): 250-8, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18818439

ABSTRACT

Soft tissue loss presents an ongoing challenge in reconstructive surgery. Local stem cell application has recently been suggested as a possible novel therapy. In the present study we evaluated the potential of a silk fibroin-chitosan (SFCS) scaffold serving as a delivery vehicle for human adipose-derived stem cells (ASCs) in a murine soft tissue injury model. Green fluorescent protein (GFP)-labeled ASCs were seeded on SFCS scaffolds at a density of 1 x 10(5) ASCs per cm(2) for 48 hours and then suture-inlaid to a 6-mm, full-thickness skin defect in 6-week-old male athymic mice. Wound healing was tracked for 2 weeks by planimetry. Histology was evaluated at 2 and 4 weeks. Our data show that the extent of wound closure was significantly enhanced in the ASC-SFCS group versus SFCS and no-graft controls at postoperative day 8 (90% +/- 3% closure vs. 75% +/- 11% and 55% +/- 17%, respectively). Microvessel density at wound bed biopsy sites from 2 weeks postoperative was significantly higher in the ASC-SFCS group versus SFCS alone (7.5 +/- 1.1 vs. 5.1 +/- 1.0 vessels per high-power field). Engrafted stem cells were positive for the fibroblastic marker heat shock protein 47, smooth muscle actin, and von Willebrand factor at both 2 and 4 weeks. GFP-positive stem cells were also found to differentiate into epidermal epithelial cells at 4 weeks postoperative. In conclusion, human adipose-derived stem cells seeded on a silk fibroin-chitosan scaffold enhance wound healing and show differentiation into fibrovascular, endothelial, and epithelial components of restored tissue.


Subject(s)
Adipose Tissue/cytology , Fibroins/metabolism , Silk/metabolism , Skin/pathology , Stem Cells/cytology , Tissue Scaffolds , Wound Healing , Animals , Biopsy , Chitosan/metabolism , Dermatologic Surgical Procedures , Disease Models, Animal , Fluorescent Antibody Technique , Mice , Regeneration , Skin/blood supply , Stem Cell Transplantation
17.
Arch Dermatol Res ; 300(5): 263-7, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18305946

ABSTRACT

Environmental ultraviolet (UV) exposure exacts a significant toll annually in terms of overall morbidity and undesirable esthetic effects of skin aging. In order to establish the molecular and pathologic basis of this process, the murine model of ultraviolet B (UVB)-induced aging has long been used with reproducibility and success. Although morphometric and histological endpoints have been useful tools to describe this model historically, they fail to allow for the real time monitoring of the aging process, and do not fully account for effects of the in vivo environment on cutaneous strata with aging. The objective of the present study was to evaluate the ability of high-resolution magnetic resonance imaging (MRI) to characterize the murine model of photoaging throughout the aging process. Six-week-old male nu/nu mice were exposed to narrow-band UVB at 30 min intervals five times weekly for 10 weeks, resulting in a characteristic photoaged morphometric result. MRI scans were performed using a 7 tesla (7 T) small animal imaging platform at pre-exposure baseline at 4 and 10 weeks. Histological analysis of full-thickness biopsies taken in 10 week photoaged mice was correlated with MRI findings, and was compared against control animals receiving no ultraviolet radiation. MRI studies revealed a statistically significant prominent evolution of epidermal hyperplasia at 4 weeks versus baseline and at 10 weeks compared to 4 week values (0.172 +/- 0.017 mm versus undetectable, P < or = 0.05; 0.258 +/- 0.007 versus 0.172 +/- 0.017 mm, P < or = 0.05, respectively). A parallel trend of dermal hyperplasia which approached statistical significance was likewise noted at 10 weeks compared to baseline values (0.420 +/- 0.073 versus 0.295 +/- 0.078 mm, P = 0.06). Histology confirmed the progressive epidermal hyperplastic change characterized by MRI findings. This study validates the novel use of high-resolution MRI for study of the murine photoaging model and establishes its potential to describe progressive cutaneous pathology in such an experimental setting.


Subject(s)
Magnetic Resonance Imaging , Skin Aging/radiation effects , Skin/pathology , Animals , Biopsy , Male , Mice , Mice, Nude , Models, Biological , Radiation Injuries, Experimental/diagnostic imaging , Radiography , Reproducibility of Results , Skin/radiation effects , Skin Aging/pathology , Skin Diseases/diagnostic imaging , Ultraviolet Rays/adverse effects
18.
Biomaterials ; 29(10): 1431-42, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18191190

ABSTRACT

The aim of the present study was to evaluate the potential of acellular dermal matrix as a carrier for delivery of stem cells to the site of soft tissue defect in a murine skin injury model and to determine the potential of stem cells delivered via such an approach to successfully engraft, survive and differentiate locally. We showed that adipose-derived stem cells delivered via this matrix survived after in vivo engraftment, spontaneously differentiated along vascular endothelial, fibroblastic and epidermal epithelial lineages and significantly improved wound healing. Furthermore, an organ survey for transplanted cells showed no evidence of a systemic distribution beyond the cutaneous wound site, indicating that the adipose-derived stem cell-dermal matrix construct provides a novel and effective method for anatomically focused cellular therapy. In conclusion, stem cell-seeded dermal matrix is an effective means for targeted in vivo cell delivery for enhanced soft tissue regeneration.


Subject(s)
Adipose Tissue/cytology , Dermis/metabolism , Stem Cell Transplantation/methods , Stem Cells/cytology , Animals , Extracellular Matrix/metabolism , Flow Cytometry , Fluorescent Antibody Technique , Humans , Mice
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