Presence of Cartilage Stem/Progenitor Cells in Adult Mice Auricular Perichondrium

BACKGROUND: Based on evidence from several other tissues, cartilage stem/progenitor cells in the auricular cartilage presumably contribute to tissue development or homeostasis of the auricle. However, no definitive studies have identified or characterized a stem/progenitor population in mice auricle. METHODOLOGY/PRINCIPAL FINDINGS: The 5-bromo-2'-deoxyuridine (BrdU) label-retaining technique was used to label dividing cells in fetal mice. Observations one year following the labeling revealed that label-retaining cells (LRCs) were present specifically in auricular perichondrium at a rate of 0.08±0.06%, but LRCs were not present in chondrium. Furthermore, LRCs were successfully isolated and cultivated from auricular cartilage. Immunocytochemical analyses showed that LRCs express CD44 and integrin-α(5). These LRCs, putative stem/progenitor cells, possess clonogenicity and chondrogenic capability in vitro. CONCLUSIONS/SIGNIFICANCE: We have identified a population of putative cartilage stem/progenitor cells in the auricular perichondrium of mice. Further characterization and utilization of the cell population should improve our understanding of basic cartilage biology and lead to advances in cartilage tissue engineering and novel therapeutic strategies for patients with craniofacial defects, including long-term tissue restoration

HAMAMATSU-ICG study: Protocol for a phase III, multicentre, single-arm study to assess the usefulness of indocyanine green fluorescent lymphography in assessing secondary lymphoedema

Introduction Secondary lymphoedema of the extremities is an important quality-of-life issue for patients who were treated for their malignancies. Indocyanine green (ICG) fluorescent lymphography may be helpful for assessing lymphoedema and for planning lymphaticovenular anastomosis (LVA). The objective of the present clinical trial is to confirm whether or not ICG fluorescent lymphography using the near-infrared monitoring camera is useful for assessing the indication for LVA, for the identification of the lymphatic vessels before the conduct of LVA, and for the confirmation of the patency of the anastomosis site during surgery. Methods and analysis This trial is a phase III, multicentre, single-arm, open-label clinical trial to assess the efficacy and safety of ICG fluorescent lymphography when assessing and treating lymphoedema of patients with secondary lymphoedema who are under consideration for LVA. The primary endpoint is the identification rate of the lymphatic vessels at the incision site based on ICG fluorescent lymphograms obtained before surgery. The secondary endpoints are 1) the sensitivity and specificity of dermal back flow determined by ICG fluorescent lymphography as compared with 99mTc lymphoscintigraphy—one of the standard diagnostic methods and 2) the usefulness of ICG fluorescent lymphography when confirming the patency of the anastomosis site after LVA. Ethics and dissemination The protocol for the study was approved by the Institutional Review Board of each institution. The trial was filed for and registered at the Pharmaceuticals and Medical Devices Agency in Japan. The trial is currently on-going and is scheduled to end in June 2020

Protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes.

To examine the cell-protective role of podocyte autophagy against glomerular endothelial dysfunction in diabetes, we analyzed the renal phenotype of tamoxifen (TM)-inducible podocyte-specific Atg5-deficient (iPodo-Atg5-/-) mice with experimental endothelial dysfunction. In both control and iPodo-Atg5-/- mice, high fat diet (HFD) feeding induced glomerular endothelial damage characterized by decreased urinary nitric oxide (NO) excretion, collapsed endothelial fenestrae, and reduced endothelial glycocalyx. HFD-fed control mice showed slight albuminuria and nearly normal podocyte morphology. In contrast, HFD-fed iPodo-Atg5-/- mice developed massive albuminuria accompanied by severe podocyte injury that was observed predominantly in podocytes adjacent to damaged endothelial cells by scanning electron microscopy. Although podocyte-specific autophagy deficiency did not affect endothelial NO synthase deficiency-associated albuminuria, it markedly exacerbated albuminuria and severe podocyte morphological damage when the damage was induced by intravenous neuraminidase injection to remove glycocalyx from the endothelial surface. Furthermore, endoplasmic reticulum stress was accelerated in podocytes of iPodo-Atg5-/- mice stimulated with neuraminidase, and treatment with molecular chaperone tauroursodeoxycholic acid improved neuraminidase-induced severe albuminuria and podocyte injury. In conclusion, podocyte autophagy plays a renoprotective role against diabetes-related structural endothelial damage, providing an additional insight into the pathogenesis of massive proteinuria in diabetic nephropathy

Ketone bodies : A double-edged sword for mammalian life span.

Accumulating evidence suggests health benefits of ketone bodies, and especially for longevity. However, the precise role of endogenous ketogenesis in mammalian life span, and the safety and efficacy of the long-term exogenous supplementation of ketone bodies remain unclear. In the present study, we show that a deficiency in endogenous ketogenesis, induced by whole-body Hmgcs2 deletion, shortens life span in mice, and that this is prevented by daily ketone body supplementation using a diet containing 1,3-butanediol, a precursor of β-hydroxybutyrate. Furthermore, feeding the 1,3-butanediol-containing diet from early in life increases midlife mortality in normal mice, but in aged mice it extends life span and prevents the high mortality associated with atherosclerosis in ApoE-deficient mice. By contrast, an ad libitum low-carbohydrate ketogenic diet markedly increases mortality. In conclusion, endogenous ketogenesis affects mammalian survival, and ketone body supplementation may represent a double-edged sword with respect to survival, depending on the method of administration and health status

Recurrence of kyphotic deformity following implant removal in pediatric pure discoligamentous Chance-type injury: A case report

Pediatric pure discoligamentous Chance-type injury is relatively rare and the appropriate surgical method has not yet been established, particularly, whether spinal fixation with fusion or without fusion is more effective. This case report describes a 10-year-old-boy who sustained an L2-3 pure discoligamentous Chance-type injury following a car accident and underwent an L2-3 posterior fixation without fusion. The implants were removed after eight months of an uneventful postoperative course. However, four months later, the kyphotic deformity recurred. Although the deformity gradually progressed over nine months, the patient remained neurologically intact and asymptomatic. This report suggests that fixation without fusion may not be appropriate in pediatric patients with pure discoligamentous Chance-type injuries. Spinal fixation with fusion may be recommended to prevent loss of correction and ensure secure stabilization

Extensive brain infarctions from bilateral vertebral artery injury because of cervical hyperextension injury: A case report

Vertebral artery injury (VAI) is not uncommon following blunt neck trauma, although bilateral VAI—which is rarer—can be fatal. We present the case of a 77-year-old man who was transported with a head injury and consciousness disorder. No hemorrhagic lesions in the patient’s head were noted using computed tomography (CT). Mild anterior opening between the fourth and fifth cervical vertebrae (C4 and C5) and multiple spinous process fractures between C4 and the first thoracic vertebrae (T1) were detected. No CT findings suggestive of VAI were noted. Brain magnetic resonance imaging (MRI) findings showed extensive brain infarctions, bilateral VAI, anterior longitudinal ligament injury, disc injury at C4/5, and retropharyngeal hematoma. He was admitted to the intensive care unit, but his family refused invasive surgical treatment; he died 6 days after admission. The extensive brain infarctions were considered to be associated with bilateral VAI because of cervical hyperextension injury. This case highlighted the importance of considering brain ischemia due to VAI, as a differential diagnosis, in patients with consciousness disorder and possible cervical hyperextension injuries, even in the absence of CT findings suggestive of VAI. In such patients, CT angiography should be performed early to evaluate the possibility of VAI

Development of a Method for Scaffold-Free Elastic Cartilage Creation

Microtia is a congenital aplasia of the auricular cartilage. Conventionally, autologous costal cartilage grafts are collected and shaped for transplantation. However, in this method, excessive invasion occurs due to limitations in the costal cartilage collection. Due to deformation over time after transplantation of the shaped graft, problems with long-term morphological maintenance exist. Additionally, the lack of elasticity with costal cartilage grafts is worth mentioning, as costal cartilage is a type of hyaline cartilage. Medical plastic materials have been transplanted as alternatives to costal cartilage, but transplant rejection and deformation over time are inevitable. It is imperative to create tissues for transplantation using cells of biological origin. Hence, cartilage tissues were developed using a biodegradable scaffold material. However, such materials suffer from transplant rejection and biodegradation, causing the transplanted cartilage tissue to deform due to a lack of elasticity. To address this problem, we established a method for creating elastic cartilage tissue for transplantation with autologous cells without using scaffold materials. Chondrocyte progenitor cells were collected from perichondrial tissue of the ear cartilage. By using a multilayer culture and a three-dimensional rotating suspension culture vessel system, we succeeded in creating scaffold-free elastic cartilage from cartilage progenitor cells