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Manstein, Dieter

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Manstein

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Dieter

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Manstein, Dieter
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    Enhanced quantification of metabolic activity for individual adipocytes by label-free FLIM
    (Nature Publishing Group UK, 2018) Evers, Michael; Salma, Nunciada; Osseiran, Sam; Casper, Malte; Birngruber, Reginald; Evans, Conor; Manstein, Dieter
    Fluorescence lifetime imaging microscopy (FLIM) of intrinsic fluorophores such as nicotinamide adenine dinucleotide (NADH) allows for label-free quantification of metabolic activity of individual cells over time and in response to various stimuli, which is not feasible using traditional methods due to their destructive nature and lack of spatial information. This study uses FLIM to measure pharmacologically induced metabolic changes that occur during the browning of white fat. Adipocyte browning increases energy expenditure, making it a desirable prospect for treating obesity and related disorders. Expanding from the traditional two-lifetime model of NADH to a four-lifetime model using exponential fitting and phasor analysis of the fluorescence decay results in superior metabolic assessment compared to traditional FLIM analysis. The four lifetime components can also be mapped to specific cellular compartments to create a novel optical ratio that quantitatively reflects changes in mitochondrial and cytosolic NADH concentrations and binding states. This widely applicable approach constitutes a powerful tool for studies where monitoring cellular metabolism is of key interest.
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    Fractional laser exposure induces neutrophil infiltration (N1 phenotype) into the tumor and stimulates systemic anti-tumor immune response
    (Public Library of Science, 2017) Kawakubo, Masayoshi; Demehri, Shadmehr; Manstein, Dieter
    Background: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP. Methodology/Principal findings We used a fractional CO2 laser to treat a tumor established by BALB/c colon carcinoma cell line (CT26.CL25), which expressed a tumor antigen, beta-galactosidase (beta-gal). aFP treated tumors grew significantly slower as compared to untreated controls. Complete remission after a single aFP treatment was observed in 47% of the mice. All survival mice from the tumor inoculation rejected re-inoculation of the CT26.CL25 colon carcinoma cells and moreover 80% of the survival mice rejected CT26 wild type colon carcinoma cells, which are parental cells of CT26.CL25 cells. Histologic section of the FP-treated tumors showed infiltrating neutrophil in the tumor early after aFP treatment. Flow cytometric analysis of tumor-infiltrating lymphocytes showed aFP treatment abrogated the increase in regulatory T lymphocyte (Treg), which suppresses anti-tumor immunity and elicited the expansion of epitope-specific CD8+ T lymphocytes, which were required to mediate the tumor-suppressing effect of aFP. Conclusion: We have demonstrated that aFP is able to induce a systemic anti-tumor adaptive immunity preventing tumor recurrence in a murine colon carcinoma in a mouse model. This study demonstrates a potential role of aFP treatments in oncology and further studies should be performed.
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    Fractional Laser Releases Tumor-Associated Antigens in Poorly Immunogenic Tumor and Induces Systemic Immunity
    (Nature Publishing Group UK, 2017) Kawakubo, Masayoshi; Cunningham, Trevor J.; Demehri, Shadmehr; Manstein, Dieter
    Currently ablative fractional photothermolysis (aFP) with CO2 laser is used for a wide variety of dermatological indications. This study presents and discusses the utility of aFP for treating oncological indications. We used a fractional CO2 laser and anti-PD-1 inhibitor to treat a tumor established unilaterally by the CT26 wild type (CT26WT) colon carcinoma cell line. Inoculated tumors grew significantly slower in aFP-treated groups (aFP and aFP + anti-PD-1 groups) and complete remission was observed in the aFP-treated groups. Flow cytometric analysis showed aFP treatment elicited an increase of CD3+, CD4+, CD8+ vand epitope specific CD8+ T cells. Moreover, the ratio of CD8+ T cells to Treg increased in the aFP-treated groups. Additionally, we established a bilateral CT26WT-inoculated mouse model, treating tumors on one-side and observing both tumors. Interestingly, tumors grew significantly slower in the aFP + anti-PD-1 groups and complete remission was observed for tumors on both aFP-treated and untreated sides. This study has demonstrated a potential role of aFP treatments in oncology.
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    Measuring Temperature Induced Phase Change Kinetics in Subcutaneous Adipose Tissues Using Near Infrared Spectroscopy, MR Imaging and Spectroscopy and OCT
    (Nature Publishing Group UK, 2017) Sajjadi, Amir; Manstein, Dieter; Carp, Stefan
    Monitoring phase transition in adipose tissue and formation of lipid crystals is important in Cryo-procedures such as Selective Cryolipolysis (SC). We exploited a Near-Infrared Spectroscopy (NIRS) method to monitor the onset of fat phase transition (freezing/melting) in human abdominal adipose tissue. The changes in optical scattering were compared to Differential Scanning Calorimetry (DSC) measurements as the gold standard method for measuring phase transition. For some samples, concurrent in vitro measurements of optical scattering using NIRS and the MR signal parameters (T2*) as well as spectral parameters using MR Spectroscopy were performed in a 3 T MR scanner during a cooling/heating cycle. To further investigate phase-transition in adipose tissue in microscopic level, an identical cooling/heating procedure was replicated on a small piece of fat harvested from the same tissue while being imaged under Optical Coherence Tomography (OCT). For all methods, their relationship with temperature shows inflexions in a narrow range, characteristic of lipid phase transition. In particular, the good agreement between DSC and Optical measurements suggests that such NIRS methods can be used to improve dosimetry and to minimize variations of clinical outcome for cryo-procedures.