An adipose extracellular matrix-derived biomaterial for soft tissue reconstruction

Soft tissue defects can result from traumatic injury, congenital defects, and medical procedures such as tumor resection. Patients who require soft tissue reconstruction have limited options and often must use autologous tissue for reconstruction, which has the adverse effects of donor site morbidity. This study explores the development of an adipose extracellular matrix – based biomaterial for the repair of soft tissue defects. The adipose extracellular matrix (ECM) is obtained through mechanical and chemical treatments to remove all the cells and lipids from intact human adipose tissue. The degradation properties of the ECM-based biomaterial can be modulated with chemical crosslinking, allowing for control over the degradation rate of the biomaterial. Material characterization of the adipose ECM was carried out through proteomics, mechanical testing, and thermal analysis. The adipose matrix supported adipose stem cell growth and differentiation in vitro, providing tissue-specific bioactive cues to improve adipogenic differentiation. In vivo biocompatibility studies showed minimal inflammatory response to the biomaterial and stable volume retention through 12 week studies. When compared with the clinical standard of fat grafting, the acellular adipose matrix demonstrated the advantages of facilitating new adipose tissue regeneration rather than relying on transplantation of autologous fat which has the risk of necrosis, cyst formation and calcification due to the limited viability of transplanted adipocytes. The adipose ECM can also be used with adipose stem cell delivery, providing a protective environment for stem cell engraftment, which in turn facilitates new adipose tissue formation. The adipose matrix provides a versatile biomaterial for soft tissue regeneration hat can be used for allogenic applications, circumventing the need for autologous tissue for reconstruction

Efficiently Correcting Matrix Products

We study the problem of efficiently correcting an erroneous product of two $n\times n$ matrices over a ring. Among other things, we provide a randomized algorithm for correcting a matrix product with at most $k$ erroneous entries running in $\tilde{O}(n^2+kn)$ time and a deterministic $\tilde{O}(kn^2)$-time algorithm for this problem (where the notation $\tilde{O}$ suppresses polylogarithmic terms in $n$ and $k$).Comment: Fixed invalid reference to figure in v

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

An adipose extracellular matrix-derived biomaterial for soft tissue reconstruction

Soft tissue defects can result from traumatic injury, congenital defects, and medical procedures such as tumor resection. Patients who require soft tissue reconstruction have limited options and often must use autologous tissue for reconstruction, which has the adverse effects of donor site morbidity. This study explores the development of an adipose extracellular matrix – based biomaterial for the repair of soft tissue defects. The adipose extracellular matrix (ECM) is obtained through mechanical and chemical treatments to remove all the cells and lipids from intact human adipose tissue. The degradation properties of the ECM-based biomaterial can be modulated with chemical crosslinking, allowing for control over the degradation rate of the biomaterial. Material characterization of the adipose ECM was carried out through proteomics, mechanical testing, and thermal analysis. The adipose matrix supported adipose stem cell growth and differentiation in vitro, providing tissue-specific bioactive cues to improve adipogenic differentiation. In vivo biocompatibility studies showed minimal inflammatory response to the biomaterial and stable volume retention through 12 week studies. When compared with the clinical standard of fat grafting, the acellular adipose matrix demonstrated the advantages of facilitating new adipose tissue regeneration rather than relying on transplantation of autologous fat which has the risk of necrosis, cyst formation and calcification due to the limited viability of transplanted adipocytes. The adipose ECM can also be used with adipose stem cell delivery, providing a protective environment for stem cell engraftment, which in turn facilitates new adipose tissue formation. The adipose matrix provides a versatile biomaterial for soft tissue regeneration hat can be used for allogenic applications, circumventing the need for autologous tissue for reconstruction

Emergence of Decapod iridescent virus 1 in cultured shrimp from Taiwan in 2020

Abstract Objectives This study was to identify and characterize Decapod iridescent virus 1 (DIV1) in the outbreaks reported in two whiteleg shrimp farms and one black tiger shrimp farm located in northern Taiwan in 2020. Methods The histopathology, electron microscopy and polymerase chain reaction (PCR) specific for the DIV1 were used to identify the virus, and the phylogenetic analysis was performed by comparing the major capsid protein gene fragment of DIV1s from Taiwan with reference sequences of the family Iridoviridae. Results DIV1 was identified by diagnostic PCR and caused mild mortality (20%) in cultured Penaeus monodon and high mortality (100%) in cultured whiteleg shrimp. Cultured P. monodon was first found to be infected with DIV1 through natural route of infection. Histopathological examination showed dark‐eosinophilic cytoplasmic inclusions in the degenerative cells of targeted hematopoietic tissues. For electron microscopy, a non‐enveloped virus particle was observed from homogenates of mixed target organs through negative staining with a diameter of 112±2 nm. Nucleotide sequences of DIV1 isolates from the Taiwanese outbreak are 100% identical to those from the PRC. Conclusions Based on the clinical evidence, mortality rates, histopathology, electron microscopy examinations and phylogenetic analysis, it is believed that DIV1 is the causative agent of the outbreak. This is the first report of DIV1 in cultured shrimp in Taiwan. The emergence of DIV1 signals a warning to shrimp aquaculture farmers worldwide

Comparison of 3 techniques of fat grafting and cell-supplemented lipotransfer in athymic rats: a pilot study

Given the wide application of autologous fat grafting, a new emphasis on fat processing techniques has emerged in an effort to limit unpredictable degrees of resorption often seen with this procedure. With the growing interest in regenerative medicine, approaches to supplement fat grafts with adipose-derived stem cells are evolving in hopes of promoting vascularization and neoadipogenesis. The authors evaluated the outcomes of the most common processing techniques for fat grafting--decantation, washing, high-speed centrifugation--and stromal vascular cell-supplemented lipotransfer to determine which method yields a higher percentage of retention and better quality graft. A total of 32 subcutaneous injections of processed human lipoaspirate were carried out in 8 athymic rats. Each animal received all 4 processing conditions, with end points at 4, 8, and 12 weeks postinjection. Evaluation of graft survival included serial measurements of volume retention and histologic analysis. At 12 weeks postinjection, cell-supplemented and centrifuged grafts showed the most consistent volume maintenance. Based on histologic analysis, cell-supplemented and washed grafts had higher scores of viability and vascularity, with the former presenting the least cystic necrosis and calcification as well as minimal inflammation. Cell-supplemented lipotransfer had optimal outcomes for graft retention, viability, and vascularity, while washing resulted in high viability with a less intensive process. High-speed centrifugation resulted in consistent volume retention but lower viability. Each of these approaches is ideal under different circumstances and contributes to the versatility and reliability of fat grafting