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| 1 | Validation of a novel animal model for sciatic nerve repair with an adipose-derived stem cell loaded fibrin conduit显示文摘Despite the regenerative capabilities of peripheral nerves, severe injuries or neuronal trauma of critical size impose immense hurdles for proper restoration of neuro-muscular circuitry. Autologous nerve grafts improve re-establishment of connectivity, but also comprise substantial donor site morbidity. We developed a rat model which allows the testing of different cell applications, i.e., mesenchymal stem cells, to improve nerve regeneration in vivo. To mimic inaccurate alignment of autologous nerve grafts with the injured nerve, a 20 mm portion of the sciatic nerve was excised, and sutured back in place in reversed direction. To validate the feasibility of our novel model, a fibrin gel conduit containing autologous undifferentiated adipose-derived stem cells was applied around the coaptation sites and compared to autologous nerve grafts. After evaluating sciatic nerve function for 16 weeks postoperatively, animals were sacrificed, and gastrocnemius muscle weight was determined along with morphological parameters(g-ratio, axon density & diameter) of regenerating axons. Interestingly, the addition of undifferentiated adipose-derived stem cells resulted in a significantly improved re-myelination, axon ingrowth and functional outcome, when compared to animals without a cell seeded conduit. The presented model thus displays several intriguing features: it imitates a certain mismatch in size, distribution and orientation of axons within the nerve coaptation site. The fibrin conduit itself allows for an easy application of cells and, as a true critical-size defect model, any observed improvement relates directly to the performed intervention. Since fibrin and adipose-derived stem cells have been approved for human applications, the technique can theoretically be performed on humans. Thus, we suggest that the model is a powerful tool to investigate cell mediated assistance of peripheral nerve regeneration. | Maximilian M.Saller Rosa-Eva Huettl Julius M.Mayer Annette Feuchtinger Christian Krug Thomas Holzbach Elias Volkmer | 2018 | Neural Regeneration Research2018，13，5： | 4 |
| 2 | Spatial metabolomics for evaluating response to neoadjuvant therapy in non-small cell lung cancer patients显示文摘Background:The response to neoadjuvant chemotherapy(NAC)differs substantially among individual patients with non-small cell lung cancer(NSCLC).Major pathological response(MPR)is a histomorphological read-out used to assess treatment response and prognosis in patientsNSCLC afterNAC.Although spatial metabolomics is a promising tool for evaluating metabolic phenotypes,it has not yet been utilized to assess therapy responses in patients with NSCLC.We evaluated the potential application of spatial metabolomics in cancer tissues to assess the response to NAC,using a metabolic classifier that utilizes mass spectrometry imaging combined with machine learning.Methods:Resected NSCLC tissue specimens obtained after NAC(n=88)were subjected to high-resolution mass spectrometry,and these data were used to develop an approach for assessing the response to NAC in patients with NSCLC.The specificities of the generated tumor cell and stroma classifiers were validated by applying this approach to a cohort of biologically matched chemotherapy-naive patients with NSCLC(n=85).Results:The developed tumor cell metabolic classifier stratified patients into different prognostic groups with 81.6%accuracy,whereas the stroma metabolic classifier displayed 78.4%accuracy.By contrast,the accuracies of MPR and TNM staging for stratification were 62.5%and 54.1%,respectively.The combination of metabolic and MPR classifiers showed slightly lower accuracy than either individual metabolic classifier.In multivariate analysis,metabolic classifiers were the only independent prognostic factors identified(tumor:P=0.001,hazards ratio[HR]=3.823,95%confidence interval[CI]=1.716-8.514;stroma:P=0.049,HR=2.180,95%CI=1.004-4.737),whereasMPR(P=0.804;HR=0.913;95%CI=0.445-1.874)and TNM staging(P=0.078;HR=1.223;95%CI=0.977-1.550)were not independent prognostic factors.Using Kaplan-Meier survival analyses,both tumor and stroma metabolic classifiers were able to further stratify patients as NAC responders(P<0.001)and non-responders(P<0.001).Conclusions:Our findings indicate that the metabolic constitutions of both tumor cells and the stroma are valuable additions to the classical histomorphology-based assessment of tumor response. | Jian Shen Na Sun Philipp Zens Thomas Kunzke Achim Buck Verena M.Prade Jun Wang Qian Wang Ronggui Hu Annette Feuchtinger Sabina Berezowska Axel Walch | 2022 | Cancer Communications2022，42，6： | 3 |
| 3 | Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria显示文摘 | Michaela Aichler Mareike Elsner Natalie Ludyga Annette Feuchtinger Verena Zangen Stefan K Maier Benjamin Balluff Cédrik Sch?ne Ludwig Hierber Herbert Braselmann Stephan Meding Sandra Rauser Hans Zischka Michaela Aubele Manfred Schmitt Marcus Feith Stefani | 2013 | J Pathol2013，，4： | 1 |
| 4 | Clinical response to chemotherapy in oesophageal adenocarcinoma patients is linked to defects in mitochondria显示文摘 | Michaela Aichler Mareike Elsner Natalie Ludyga Annette Feuchtinger Verena Zangen Stefan K Maier Benjamin Balluff Cédrik Sch?ne Ludwig Hierber Herbert Braselmann Stephan Meding Sandra Rauser Hans Zischka Michaela Aubele Manfred Schmitt Marcus Feith Stefani | 2013 | J Pathol2013，，4： | 1 |
| 5 | Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model显示文摘Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells(ADSPCs)in peripheral nerve recovery.Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs.This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned(2%oxygen for 72 hours)autologous ADSPCs(n=9).This treatment mode was compared with three others:fibrin conduit seeded with ADSPCs cultivated under normoxic conditions(n=9);non-cell-carrying conduit(n=9);and nerve autograft only(n=9).A 16-week follow-up included functional testing(sciatic functional index and static sciatic index)as well as postmortem muscle mass analyses and morphometric nerve evaluations(histology,g-ratio,axon density,and diameter).At 8 weeks,the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups,indicating faster functional regeneration.Furthermore,histologic evaluation showed significantly increased axon outgrowth/branching,axon density,remyelination,and a reduced relative connective tissue area.Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts.Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice. | Julius M.Mayer Christian Krug Maximilian M.Saller Annette Feuchtinger Riccardo E.Giunta Elias Volkmer Thomas Holzbach | 2023 | Neural Regeneration Research2023，18，3： | 0 |
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