Good manufacturing practice production of an off-the-shelf CD34 progenitor-derived NK cell product with preserved anti-tumor functionality post-infusion in NOD/SCID/IL2Rg mice.

The adoptive transfer of natural killer (NK) cells represents a promising cancer therapy due to their intrinsic ability to distinguish between malignant and healthy cells in an allogeneic context, enabling off-the-shelf manufacturing possibilities. On demand availability of cryopreserved advanced therapy medicinal products (ATMPs) could promote enrolment in clinical trials and eventually commercialization with repeated dosing possibilities. However, NK cells are considered highly sensitive to cryopreservation-induced defects, including impaired viability, anti-tumor cytotoxicity, and in vivo expansion capacity.

Interleukin-12 decorated nanosized semiflexible Immunofilaments enable directed targeting and augmented IFNγ responses of natural killer cells.

Immunotherapies are a powerful strategy to treat cancer by modulating the immune system to raise an anti-tumor immune response. A prime example of immunotherapies are cytokines - small immunomodulatory molecules that are widely used to stimulate immune cells. Undirected administration of cytokines, however, can cause severe side effects, preventing the use of potent cytokines, such as Interleukin (IL)-12, which induces IFNγ responses by cytotoxic effector lymphocytes, including NK cells.

Increased peritoneal TGF-β1 is associated with ascites-induced NK-cell dysfunction and reduced survival in high-grade epithelial ovarian cancer.

Natural killer (NK) cell therapy represents an attractive immunotherapy approach against recurrent epithelial ovarian cancer (EOC), as EOC is sensitive to NK cell-mediated cytotoxicity. However, NK cell antitumor activity is dampened by suppressive factors in EOC patient ascites. Here, we integrated functional assays, soluble factor analysis, high-dimensional flow cytometry cellular component data and clinical parameters of advanced EOC patients to study the mechanisms of ascites-induced inhibition of NK cells.

Engineering of CD34+ progenitor-derived natural killer cells with higher-affinity CD16a for enhanced antibody-dependent cellular cytotoxicity.

Background Aims: Natural killer (NK) cell transfer is a promising cellular immunotherapy for cancer. Previously, we developed a robust method to generate large NK cell numbers from CD34 hematopoietic stem and progenitor cells (HSPCs), which exhibit strong anti-tumor activity. However, since these cells express low levels of the Fc receptor CD16a in vitro, antibody-dependent cellular cytotoxicity (ADCC) by these cells is limited.

CD34 progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg mice.

Combining natural killer (NK) cell adoptive transfer with tumor-sensitizing chemotherapy is an attractive approach against recurrent ovarian cancer (OC), as OC is sensitive to NK cell-mediated immunity. Previously, we showed that CD34 hematopoietic progenitor cell (HPC)-derived NK cells can kill OC cells and inhibit OC tumor growth in mice. Here, we investigated the potential of HPC-NK cell therapy combined with chemotherapeutic gemcitabine (used in recurrent OC patients) against OC.

Reconstruction Strategies of the Ureter and Urinary Diversion Using Tissue Engineering Approaches.

Tissue Engineering (TE) approaches are needed to advance the field of reconstructive urology. We indicate that regeneration of ureteral tissue and the formation of a urinary diversion using TE approaches are possible, although it is currently very time-consuming and complex to achieve well-developed neotissue. Faster regeneration approaches using novel scaffolds are desirable.

The Impact of γ-Irradiation and EtO Degassing on Tissue Remodeling of Collagen-based Hybrid Tubular Templates.

Clinical implementation of novel products for tissue engineering and regenerative medicine requires a validated sterilization method. In this study, we investigated the effect of γ-irradiation and EtO degassing on material characteristics and the effect on template remodeling of hybrid tubular constructs in a large animal model. Hybrid tubular templates were prepared from type I collagen and Vicryl polymers and sterilized by 25 kGray of γ-irradiation or EtO degassing.

Ureteral Reconstruction in Goats Using Tissue-Engineered Templates and Subcutaneous Preimplantation.

Repair of long ureteral defects often requires long graft tissues and extensive surgery. This is associated with complications, including a lack of suitable tissue and graft site morbidity. Tissue engineering may provide an attractive alternative to the autologous graft tissues.

Clinical protocol levels are required in laboratory animal surgery when using medical devices: experiences with ureteral replacement surgery in goats.

It is common to test medical devices in large animal studies that are or could also be used in humans. In this short report we describe the use of a ureteral J-stent for the evaluation of biodegradable tubular constructs for tissue reconstruction, and the regeneration of ureters in Saanen goats. Similarly to a previous study in pigs, the ureteral J-stent was blindly inserted until some resistance was met.

Tissue Engineering of the Urethra: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

Context: Urethra repair by tissue engineering has been extensively studied in laboratory animals and patients, but is not routinely used in clinical practice.

Objective: To systematically investigate preclinical and clinical evidence of the efficacy of tissue engineering for urethra repair in order to stimulate translation of preclinical studies to the clinic.

Evidence Acquisition: A systematic search strategy was applied in PubMed and EMBASE.

Bladder Regeneration Using Multiple Acellular Scaffolds with Growth Factors in a Bladder.

Introduction: Tissue engineering may become an alternative to current bladder augmentation techniques. Large scaffolds are needed for clinically significant augmentation, but can result in fibrosis and graft shrinkage. The purpose of this study was to investigate the use of multiple scaffolds instead of one large scaffold, to enhance bladder tissue regeneration and bladder capacity.

Visualisation of newly synthesised collagen in vitro and in vivo.

Identifying collagen produced de novo by cells in a background of purified collagenous biomaterials poses a major problem in for example the evaluation of tissue-engineered constructs and cell biological studies to tumor dissemination. We have developed a universal strategy to detect and localize newly deposited collagen based on its inherent association with dermatan sulfate. The method is applicable irrespective of host species and collagen source.

Recent advances in ureteral tissue engineering.

Reconstruction of long ureteral defects often warrants the use of graft tissue and extensive surgical procedures to maintain the safe transport of urine from the kidneys to the urinary bladder. Complication risks, graft failure-related morbidity, and the lack of suitable tissue are major concerns. Tissue engineering might offer an alternative treatment approach in these cases, but ureteral tissue engineering is still an underreported topic in current literature.