Local delivery of allogeneic bone marrow and adipose tissue‐derived mesenchymal stromal cells for cutaneous wound healing in a porcine model

Wound healing remains a major challenge in modern medicine. Bone marrow‐ (BM) and adipose tissue‐ (AT) derived mesenchymal stromal/stem cells (MSCs) are of great interest for tissue reconstruction due to their unique immunological properties and regenerative potential. The purpose of this study was to characterize BM and AT‐MSCs and evaluate their effect when administered in a porcine wound model. MSCs were derived from male Göttingen Minipigs and characterized according to established criteria. Allogeneic BM‐ or AT‐MSCs were administered intradermally (1 x 10⁶ cells) into partial‐thickness wounds created on female animals, and covered with Vaseline® gauze or fibrin in a randomized pattern. Animals were euthanized at 7, 10, 14 and 21 days. Tissues were analyzed visually for healing and by microscopic examination for epidermal development and remodelling. Polymerase chain reaction (PCR) was used to detect the presence of male DNA in the specimens. All wounds were healed by 14 days. MSC‐injected wounds were associated with improved appearance and faster re‐epithelialization compared to saline controls. Evaluation of rete ridge depth and architecture showed that MSC treatment promoted a faster rate of epidermal maturation. Male DNA was detected in all samples at days 7 and 10, suggesting the presence of MSCs. We showed the safety, feasibility and potential efficacy of local injection of allogeneic BM‐ and AT‐MSCs for treatment of wounds in a preclinical model. Our data in this large animal model support the potential use of BM‐ and AT‐MSC for treatment of cutaneous wounds through modulation of healing and epithelialization. Copyright © 2013 John Wiley & Sons, Ltd.     

Embryonic stem cells produce neurotrophins in response to cerebral tissue extract: Cell line-dependent differences

In the present study, we compare the capacity of two different embryonic stem (ES) cell lines to secrete neurotrophins in response to cerebral tissue extract derived from healthy or injured rat brains. The intrinsic capacity of the embryonic cell lines BAC7 (feeder cell-dependent cultivation) to release brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) exceeded the release of these factors by CGR8 cells (feeder cell-free growth) by factors of 10 and 4, respectively. Nerve growth factor (NGF) was secreted only by BAC7 cells. Conditioning of cell lines with cerebral tissue extract derived from healthy or fluid percussion-injured rat brains resulted in a significant time-dependent increase in BDNF release in both cell lines. The increase in BDNF release by BAC7 cells was more pronounced when cells were incubated with brain extract derived from injured brain. However, differences in neurotrophin release associated with the origin of brain extract were at no time statistically significant. Neutrophin-3 and NGF release was inhibited when cell lines were exposed to cerebral tissue extract. The magnitude of the response to cerebral tissue extract was dependent on the intrinsic capacity of the cell lines to release neurotrophins. Our results clearly demonstrate significant variations in the intrinsic capability of different stem cell lines to produce neurotrophic factors. Furthermore, a significant modulation of neurotrophic factor release was observed following conditioning of cell lines with tissue extract derived from rat brains. A significant modulation of neurotrophin release dependent on the source of cerebral tissue extract used was not observed.     

Parosteal osteosarcoma: case report and review of the literature

BACKGROUND: The majority of osteosarcoma cases of the head and neck are high-grade lesions. We present a case and discuss the diagnostic and therapeutic implications of a rare low-grade parosteal osteosarcoma of the maxilla. METHODS: A 32-year-old man presenting to the Head and Neck Surgical Oncology clinic with a 1-year history of a firm palatal mass. Evaluation clinically and radiographically raised the suspicion of an osteosarcoma. RESULTS: A partial maxillectomy revealed a parosteal osteosarcoma with negative margins. No adjuvant therapy was recommended, and the patient remains without evidence of local recurrence after 3 years. CONCLUSIONS: Parosteal osteosarcomas of the head and neck region are rare, low-grade variants of osteosarcoma, but have the potential to recur with simple local excision. Clinical and radiographic features are diagnostically helpful. Definitive diagnosis comes from histopathology, and wide local resection should be employed as the optimal treatment.     

A practical approach to evaluating the patient with syncope

Syncope is a significant patient care issue. There are approximately half a million cases annually. Syncope may represent a life-threatening condition or a benign process. Identifying the cause of syncope is often difficult because it occurs sporadically and the cause is usually not obvious. The literature states that as many as 25% to 50% of patients who experience syncope remain undiagnosed. Taking a very practical approach when caring for these patients includes a very detailed health history, electrocardiogram, and a logical approach based on what is known and what was learned from the patient's medical history.     

Spontaneous motor activity in the perinatal infant before and after birth: stability in individual differences.

This study was undertaken to determine if a relationship existed between the duration of spontaneous general movements before and after birth. Twenty-two infants were examined three times as fetuses between 38 and 40 weeks gestational age and three times as neonates between 2 and 4 weeks postnatal age. Motor activity level during active sleep periods was quantified by direct sonographic visualization for fetuses and by videotaped images of trunk movement for neonates. We found that both fetuses and neonates exhibited stable individual differences in motor activity level. In addition, infants who moved at a certain rate as fetuses generally moved at the same relative rate as neonates up to 4-weeks postnatal age. Our findings suggested that individual differences in motor activity level in the 1st month following birth probably arise during fetal life.     

Improved chest wall fixation for correction of pectus excavatum.

Pectus excavatum, the most common congenital chest wall abnormality, is manifested by deformity of the costal cartilages resulting in a depressed and often rotated sternum. Although there are conflicting data to support and reject the concept that physiologic improvement can be a consequence of surgical repair, correction is frequently indicated for aesthetic improvement alone. The most popular current repair involves resection of abnormal costal cartilages, sternal osteotomy and mobilisation, followed by fixation of the sternum in the corrected position. Improved fixation techniques have evolved, but generally have not employed current concepts of rigid fixation. The correction of pectus excavatum using reconstruction plates incorporates the benefits of rigid fixation, while allowing custom chest wall contouring and sternal reorientation. Reconstruction plate fixation of the sternum should be considered during correction of pectus excavatum in adult and adolescent patients.     

Molecular cytogenetic delineation of a novel critical genomic region in chromosome bands 11q22.3-923.1 in lymphoproliferative disorders.

Aberrations of the long arm of chromosome 11 are among the most common chromosome abnormalities in lymphoproliferative disorders (LPD). Translocations involving BCL1 at 11q13 are strongly associated with mantle cell lymphoma. other nonrandom aberrations, especially deletions and, less frequently, translocations, involving bands 11q21-923 have been identified by chromosome banding analysis. To date, the critical genomic segment and candidate genes involved in these deletions have not been identified. In the present study, we have analyzed tumors from 43 patients with LPD (B-cell chronic lymphocytic leukemia, n = 40; mantle cell lymphoma, n = 3) showing aberrations of bands 11q21-923 by fluorescence in situ hybridization. As probes we used Alu-PCR products from 17 yeast artificial chromosome clones spanning chromosome bands 11q14.3-923.3, including a panel of yeast artificial chromosome clones recognizing a contiguous genomic DNA fragment of approximately 9-10 Mb in bands 11q22.3-923.3. In the 41 tumors exhibiting deletions, we identified a commonly deleted segment in band 11q22.3-923.1; this region is approximately 2-3 Mb in size and contains the genes coding for ATM (ataxia telangiectasia mutated), RDX (radixin), and FDX1 (ferredoxin 1). Furthermore, two translocation break-points were localized to a 1.8-Mb genomic fragment contained within the commonly deleted segment. Thus, we have identified a single critical region of 2-3 Mb in size in which 11q14-923 aberrations in LPD cluster. This provides the basis for the identification of the gene(s) at 11q22.3-923.1 that are involved in the pathogenesis of LPD.