Christian Hohaus

Migrational changes of mesenchymal stem cells in response to cytokines, growth factors, hypoxia, and aging

Mesenchymal stem cells (MSCs) are non-immunogenic, multipotent cells with at least trilineage differentiation potential. They promote wound healing, improve regeneration of injured tissue, and mediate numerous other health effects. MSCs migrate to sites of injury and stimulate repair either through direct differentiation or indirectly through the stimulation of endogenous repair mechanisms. Using the in vitro scratch assay, we show that the inflammatory cytokines, chemokines, and growth factors TNF-α, SDF-1, PDGF, and bFGF enhance migration of rat MSCs under normoxic conditions, while TNF-α, IFN-γ, PDGF, and bFGF promote MSC migration under hypoxic conditions. This indicates that the oxygen concentration affects how MSCs will migrate in response to specific factors and, consistent with this, differential expression of cytokines was observed under hypoxic versus normoxic conditions. Using the transwell migration assay, we find that TNF-α, IFN-γ, bFGF, IGF-1, PDGF, and SDF-1 significantly increase transmigration of rat MSCs compared to unstimulated medium. MSCs derived from aged rats exhibited comparable migration to MSCs derived from young rats under hypoxic and normoxic conditions, even after application with specific factors. Similarly, migration in MSCs from aged, human donors did not statistically differ compared to migration in MSCs derived from human umbilical cord tissue or younger donors.

Clinical evaluation of a new multiparameter neuromonitoring device: measurement of brain tissue oxygen, brain temperature, and intracranial pressure.

Objective The study presented evaluated the first clinical use of a new multiparameter catheter measuring intracranial pressure (ICP), partial pressure of brain tissue oxygen (ptiO2), and brain temperature (TBr) (Neurovent PTO). To assess the validity of measured ptiO2 a second probe, which represents the current golden standard of ptiO2 measurement, was implanted (Licox system). Methods Thirty patients with indicated invasive measurement of ICP under intensive care unit conditions were included. Using a double lumen bolt, ptiO2 was measured simultaneously with Licox and Neurovent PTO. Ex vivo tests on both probes were conducted independently by the manufacturer of the Neurovent PTO (Raumedic AG, Germany). Results The average of individual mean ptiO2 measurements showed no relevant differences between the Licox (19.5±7.1) and Neurovent multiparameter probe (21.7±9.5). Twenty-eight Licox probes out of 30 showed proper functioning over the desired monitoring period. Raumedic multiparameter probes displayed a higher malfunction/handling error frequency (2 device errors, 11 handling errors). A comparison of the ptiO2 data between the Licox and Raumedic systems according to Bland and Altman was possible in 18 out of 30 patients and showed acceptable results (mean difference −1.24 mm Hg; limits of agreement: –25.1 to +22.6 mm Hg). A total of 95.2% of 96,083 recordings was within the calculated limits of agreement. Ex vivo tests of the probes after explantation revealed stable ICP and TBr function of the Raumedic probe. Precision of Zero ptiO2 did not differ between the probes, whereas precision of the 150 mm Hg ptiO2 was greater in the Raumedic probes. Conclusions Combining 3 different neuromonitoring functions in 1 probe might ease monitoring by making a second (ptiO2) probe unnecessary. Interpretation of our data is limited by several factors: (1) monocentric study; (2) reduced mechanical probe stability, handling difficulties with the double lumen bolt; (3) design changes to improve mechanical stability will require further study; (4) conflict of interest with Raumedic because of its support for the study. The conclusion drawn from our study is that the new multiparameter probe evaluated does measure ICP, TBr, and ptiO2. But all the initial data given in this paper have to be interpreted cautiously. A new study will be necessary when the mechanical stability of the new probe has been improved.

Does Brain Temperature Correlate With Intracranial Pressure

Objective A positive correlation between brain temperature and intracranial pressure (ICP) has been proposed for patients under intensive care conditions. Design and Methods Data were recorded at 5-minute intervals in patients under ICP monitoring conditions. Brain temperature: combined ICP/temperature probe (Raumedic), core temperature: indwelling urinary catheter with temperature probe (Rüsch). The correlation between brain temperature and ICP was assessed by computing an estimated mean correlation coefficient (re) and by a time series analysis. Patients Forty consecutive neurosurgical patients receiving intensive care therapy for trauma, cerebrovascular malformation, and spontaneous hemorrhage were studied. A total of 48,892 measurements (9778 h) were analyzed. No additional interventions were performed. Results The median ICP was 14 mm Hg (range: −13 to 167). The brain temperature (median 38°C; range 23.2 to 42.1) was 0.3°C (range: −3.6 to 2.6) higher than the core temperature (median 37.7°C; range 16.6 to 42.0), P<0.001. The mean Pearson correlation between ICP and brain temperature in all patients was re=0.13 (P<0.05); the time series analysis (assuming a possible lagged correlation between ICP and brain temperature) revealed a mean correlation of 0.05±0.25 (P<0.05). Both correlation coefficients indicate that any relationship between brain temperature and ICP accounts for less than 2% of the variability [coefficient of determination (r2)<0.02]. Conclusions These data do not support the notion of a clinically useful correlation between brain temperature and ICP.

Protective effects of alpha phenyl-tert-butyl nitrone and ascorbic acid in human adipose derived mesenchymal stem cells from differently aged donors

Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stem cells that promote therapeutic effects and are frequently used in autologous applications. Little is known about how ADSCs respond to genotoxic stress and whether or not donor age affects DNA damage and repair. In this study, we used the comet assay to assess DNA damage and repair in human ADSCs derived from young (20-40 years), middle-aged (41-60 years), and older (61+ years) donors following treatment with H2O2 or UV light. Tail lengths in H2O2-treated ADSCs were substantially higher than the tail lengths in UV-treated ADSCs. After 30 minutes of treatment with H2O2, ADSCs preconditioned with alpha phenyl-tert-butyl nitrone (PBN) or ascorbic acid (AA) showed a significant reduction in % tail DNA. The majority of ADSCs treated with PBN or AA displayed low olive tail movements at various timepoints. In general and indicative of DNA repair, % tail length and % tail DNA peaked at 30 minutes and then decreased to near-control levels at the 2 hour and 4 hour timepoints. Differently aged ADSCs displayed comparable levels of DNA damage in the majority of these experiments, suggesting that the age of the donor does not affect the DNA damage response in cultured ADSCs.

Irreführende Anisokorie bei komatöser 15-Jähriger mit Kopfverletzung

Anisocoria after blunt head trauma, associated with altered vigilance, is not unusually assumed to expanding intracranial mass lesion. Obvious signs of head-trauma and vomiting might strengthen this diagnosis. We report from an unconscious 15-year-old girl (Glasgow-Coma-Scale score 3) that showed these symptoms secondary after head-trauma due to alcohol intoxication but turned out to be misleading after cranial computed tomography (CT). Surprisingly, an artificial eye was found that previously remained undetected in clinical examination. Artificial eyes implemented after enucleation therapy in retinoblastoma or eye-trauma are nowadays perfectly fitting. Prehospital discrimination of artificial eyes and natural eyes might be difficult in comatose emergency patients. Neurological examination should check corneal reflex and manual palpation of the bulbus. Independent from anisocoria, patients presenting GCS 3 and head injury need rapid admission to CT-diagnostic, neurosurgical treatment respectively.

[Misleading anisocoria in a comatose 15-year-old with head injury].

Anisocoria after blunt head trauma, associated with altered vigilance, is not unusually assumed to expanding intracranial mass lesion. Obvious signs of head-trauma and vomiting might strengthen this diagnosis. We report from an unconscious 15-year-old girl (Glasgow-Coma-Scale score 3) that showed these symptoms secondary after head-trauma due to alcohol intoxication but turned out to be misleading after cranial computed tomography (CT). Surprisingly, an artificial eye was found that previously remained undetected in clinical examination. Artificial eyes implemented after enucleation therapy in retinoblastoma or eye-trauma are nowadays perfectly fitting. Prehospital discrimination of artificial eyes and natural eyes might be difficult in comatose emergency patients. Neurological examination should check corneal reflex and manual palpation of the bulbus. Independent from anisocoria, patients presenting GCS 3 and head injury need rapid admission to CT-diagnostic, neurosurgical treatment respectively.

Cell Transplantation for Lumbar Spine Degenerative Disk Disease

We designed a study using the dog as our model to investigate the hypothesis that repair of the damaged disk is technically feasible, autologous cells can be reproducibly cultured under defined and controlled conditions, percutaneous delivery is possible, and disk cells will integrate with the surrounding tissue, produce the appropriate intervertebral disk extracellular matrix, and potentially provide a functional solution to disk repair.

Behandlung spinaler Duraverletzungen

ZusammenfassungDer dichte Duraverschluss ist notwendig, weil sonst die Gefahr der Ausbildung von Liquorzysten- und (-)fisteln besteht, die schwer zu behandeln sind. In ungünstigen Fällen kann es auf diesem Weg zu aufsteigenden Infektionen kommen. Der übliche Duraverschluss erfolgt mittels Naht, es können aber auch Fibrinkleber und klebebeschichtete Vliese eingesetzt werden. Bei größeren Duradefekten werden bevorzugt autologe oder allogene Duraersatzmaterialen verwendet. Synthetische Materialien werden vielfältig angeboten, weisen etwas ungünstigere Verarbeitungseigenschaften auf, gelten aber hinsichtlich der Übertragung von Krankheitserregern als unkritischer. Im vorliegenden Beitrag wird über die Techniken des Duraverschlusses, den Einsatz von selbst klebendem Vlies und über weiterführende Techniken beim Vorliegen spinaler Duradefekte berichtet.AbstractTight dural closure is necessary to avoid the risk of liquor cysts and fistulas, which are difficult to treat. In unfavourable cases, ascending infections are promoted in this way. Dural closure is usually performed with suturing; however, fibrin glue and coated collagen membranes can be used. In the case of large dural defects, autologous or allogeneic dural replacement materials are preferably used. Although many synthetic materials are available, these are less easy to work with; however, they are considered less of a risk in terms of the transmission of pathogens. The present article reports on dural closure techniques, the use of self-gluing membrane, as well as other techniques used in the case of spinal dural defects.

Irreführende Anisokorie bei komatöser 15-Jähriger mit Kopfverletzung@@@Misleading anisocoria in a comatose 15-year-old with head injury

Anisocoria after blunt head trauma, associated with altered vigilance, is not unusually assumed to expanding intracranial mass lesion. Obvious signs of head-trauma and vomiting might strengthen this diagnosis. We report from an unconscious 15-year-old girl (Glasgow-Coma-Scale score 3) that showed these symptoms secondary after head-trauma due to alcohol intoxication but turned out to be misleading after cranial computed tomography (CT). Surprisingly, an artificial eye was found that previously remained undetected in clinical examination. Artificial eyes implemented after enucleation therapy in retinoblastoma or eye-trauma are nowadays perfectly fitting. Prehospital discrimination of artificial eyes and natural eyes might be difficult in comatose emergency patients. Neurological examination should check corneal reflex and manual palpation of the bulbus. Independent from anisocoria, patients presenting GCS 3 and head injury need rapid admission to CT-diagnostic, neurosurgical treatment respectively.