A Microbiological and Ultrastructural Comparison of Aseptic versus Sterile Acellular Dermal Matrix as a Reconstructive Material and a Scaffold for Stem Cell Ingrowth.

Background: Recent data suggest an increased risk for infection when acellular dermal matrix is used in breast reconstruction. This may be because some acellular dermal matrices are actually not terminally sterilized but are instead "aseptically processed." This study evaluates aseptic and sterile matrices for evidence of bacterial contamination and whether or not terminal sterilization affects matrix collagen architecture and stem cell ingrowth.

Regulation of ADSC Osteoinductive Potential Using Notch Pathway Inhibition and Gene Rescue: A Potential On/Off Switch for Clinical Applications in Bone Formation and Reconstructive Efforts.

Background: Although there has been tremendous research in the ability of mesenchymal-derived adipose derived stem cells (ADSCs) to form bone, less is known regarding the molecular mechanisms that regulate the osteogenic potential of ADSCs. Notch, which consists of a key family of regulatory ligands involved in bone formation, is expressed in the bone marrow-derived mesenchymal stem cell niche and is critical for proliferation, migration, and ultimately osseous differentiation. The authors investigate how Notch impacts ADSC proliferation and osteogenic differentiation to determine a translatable application of these cells in bone regeneration.

Transplantation of an LGR6+ Epithelial Stem Cell-Enriched Scaffold for Repair of Full-Thickness Soft-Tissue Defects: The In Vitro Development of Polarized Hair-Bearing Skin.

Background: Recent literature has shown that full-thickness wounds, devoid of the stem cell niche, can subsequently be reconstructed with functional skin elements following migration of the LGR6 epithelial stem cell into the wound bed. In this study, the authors use a variety of LGR6 epithelial stem cell-seeded scaffolds to determine therapeutic utility and regenerative potential in the immediate reconstruction of full-thickness wounds.

Methods: Isolated LGR6 epithelial stem cells were seeded onto a spectrum of acellular matrices and monitored in both in vitro and in vivo settings to determine their relative capacity to regenerate tissues and heal wounds.

Defining the Salvage Time Window for the Use of Ischemic Postconditioning in Skeletal Muscle Ischemia Reperfusion Injury.

Background: The aim of this study was to determine the optimal salvage time window within which ischemic postconditioning can be used to ameliorate ischemia/reperfusion (I/R) injury in skeletal muscle.

Methods: A total of 48 Sprague-Dawley rats were divided into two groups: I/R only (control) and I/R with postconditioning. Subgroups were divided by duration of ischemia (2, 4, 6, and 8 hours).

Transplantation of the LGR6+ epithelial stem cell into full-thickness cutaneous wounds results in enhanced healing, nascent hair follicle development, and augmentation of angiogenic analytes.

Background: The recently discovered leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6+) epithelial stem cell located within the follicular bulge of the adnexal compartment is capable of producing all cellular lineages of the skin. In this study, the authors sought to determine whether these cells can be transplanted for use as a type of cellular therapy for the repair of full-thickness wounds in which the native stem cell niche has been obliterated.

Methods: Full-thickness murine skin was harvested and LGR6(+GFP) epithelial stem cells were isolated using fluorescence-activated cell sorting.

Adipose-derived stem cell to epithelial stem cell transdifferentiation: a mechanism to potentially improve understanding of fat grafting's impact on skin rejuvenation.

Background: Recent evidence suggests that lipofilling improves overlying skin composition and appearance. Adipose-derived stem cells (ADSC) have been implicated.

Objective: The authors identify ADSC transdifferentiation into epithelial stem cells through coexpression of GFP+ (green fluorescent protein positive) ADSC with the epithelial stem cell marker p63 in an in vivo fat grafting model.

Stimulation of the follicular bulge LGR5+ and LGR6+ stem cells with the gut-derived human alpha defensin 5 results in decreased bacterial presence, enhanced wound healing, and hair growth from tissues devoid of adnexal structures.

Background: Discovery of leucine-rich repeat-containing G-protein-coupled receptors 5 and 6 (LGR5 and LGR6) as markers of adult epithelial stem cells of the skin and intestine permits researchers to draw on the intrinsic cellular fundamentals of wound healing and proliferation dynamics of epithelial surfaces. In this study, the authors use the intestine-derived human alpha defensin 5 to stimulate epithelial proliferation, bacterial reduction, and hair production in burn wound beds to provide the field with initial insight on augmenting wound healing in tissues devoid of adnexal stem cells.

Methods: Murine third-degree burn wound beds were treated with (1) intestine-derived human alpha defensin 5, (2) skin-derived human beta defensin 1, and (3) sulfadiazine to determine their roles in wound healing, bacterial reduction, and hair growth.

Therapeutic potential of human adipose stem cells in a cancer stem cell-like gastric cancer cell model.

Cancer stem cells (CSCs) or circulating tumor cells play an important role in tumor initiation, invasion, metastasis and resistance to anticancer therapies. Therapies that target gastric tumor CSCs have potential clinical application for preventing malignant gastric tumor progression and metastasis. We isolated CD44+ gastric cancer cells from the gastric cancer cell line AGS and Hs746T cells and maintained the cells in a novel stem cell culture.

Early growth response factor-1: expression in a rabbit flexor tendon scar model.

Background: Adhesion formation limits functional recovery after flexor tendon repair. Various growth factors have been implicated in the adhesion scar process. Early growth response factor-1 (EGR-1), a transcription factor associated with synthesis of a variety of key fibrotic growth factors and expression of extracellular matrix genes, has never been identified in a tendon repair model.

Transgene expression in a model of composite tissue allotransplantation.

Background: Composite tissue allografting may be an ideal solution to many problems requiring reconstructive surgery. Unfortunately, complications associated with chronic immunocompromise are major impediments to widespread use of composite tissue allografting. Current immunosuppressive and immunomodulatory paradigms focus on modification of the recipient through global immunosuppression or donor/recipient chimerism.

Strategies for refinement of abdominal device implantation in mice: strain, carboxymethylcellulose, thermal support, and atipamezole.

A widely used in vivo technique in mice and other species is the surgical implantation of transmitters for telemetric monitoring of core body temperature, locomotor activity, and other variables. However, these devices are quite large relative to the size of the mouse abdomen. We report here on the results of several related studies that we conducted to evaluate refinement strategies relevant to implantation of abdominal devices in mice.

Sleep, temperature, activity, and prolactin phenotypes of genetically epilepsy-prone rats.

Sleep-wake disturbances are common in epilepsy, yet the potential adverse effect of seizures on sleep is not well characterized. Genetically epilepsy-prone rats (GEPRs) are a well-studied model of genetic susceptibility to audiogenic seizures. To assess their suitability for investigating relationships between seizures and disordered sleep, we characterized the sleep, activity, and tempera ture patterns of 2 GEPR strains (designated 3 and 9) and Sprague-Dawley (SD) rats in the basal state, after forced wakefulness, and after exposure to sound-induced seizures at light onset and dark onset.

Prevention of age-related dysregulation of calcium dynamics by estrogen in neurons.

To determine the impact of aging and 17beta-estradiol on neuronal Ca2+ homeostasis, intracellular Fura-2 Ca2+-imaging was conducted during 20-pulses of glutamate in hippocampal neurons cultured from embryonic (E18), middle-age (10 months) and old (24 months) rat brain. Marked age-related differences in intracellular Ca2+ ([Ca2+]i) homeostasis and striking regulation by 17beta-estradiol were seen. Embryonic neurons exhibited the greatest capacity to regulate Ca2+ homeostasis followed by middle-age neurons.