3.1] Mesenchymal stromal cells modulate infection and inflammation in the uterus and mammary gland

The use of mesenchymal stromal cells (MSCs) is emerging as an efficacious and safe treatment for many infectious and non-infectious inflammatory diseases in human and veterinary medicine. Such use could be done to treat mastitis and metritis, which are the most common disease conditions affecting dairy cows leading to considerable economic losses and reduced animal welfare. Currently, both disease conditions are commonly treated using local and systemic administration of antibiotics. However, this strategy has many disadvantages including low cure rates and the public health hazards. Looking for alternative approaches, we investigated the properties of MSCs using in-vitro mammary and endometrial cell systems and in-vivo mastitis and metritis murine model systems. In-vitro, co-culture of mammary and uterus epithelial cells constructed with NF-kB reporter system, the master regulator of inflammation, demonstrated their anti-inflammatory effects in response to.LPS. In vivo, we challenge animals with field strains of mammary and utero pathogenic Escherichia coli and evaluated the effects of local and systemic application of MSC in the animal models. Disease outcome was evaluated using histological analysis, bacterial counts and gene expression of inflammatory markers. We show that MSC treatment reduced bacterial load in metritis and significantly modulated the inflammatory response of the uterus and mammary gland to bacterial infection. Most notably are the immune modulatory effects of remotely engrafted intravenous MSCs, which open new avenues to the development of MSC-based cell-free therapies.   

3.2] Cultured meat and alternative proteins

Climate change is threatening the future food availability of the world population, posing a major challenge faced by societies and governments. The awareness of emerging climate change increases the global demand for alternative protein sources, therefore a pressing need to develop more sustainable sources of proteins is arising. Cellular agriculture is an evolving branch of biotechnology that aims to develop new solutions and improve the old ones, including plant-based substitutes and cell-based meats and dairy products. One of the proposed solutions is cultured meat (CM), an alternative protein source that has flourished in recent years as the demand for CM products has risen. Cultured meat (CM) is an emerging technology based on the proliferation and differentiation of animal stem cells in vitro to produce edible tissues for human consumption. However, a significant improvement is needed for the process to become cost-effective and reliable enough to bring it to production on a scale suitable for the food supply. This session aims to address these challenges by bringing together scientists, policymakers and entrepreneurs to discuss aims to revolutionize the way we produce meat, showcase recent success by Israeli scientists and startups, and discuss future challenges. This session also addresses the ways governments and investors can focus on funding plans worldwide toward a sustainable way to feed humanity's future meat demands. The move from traditional farm-animal-agriculture-based nutrition to cultured meat will directly contribute to the efficient utilization of environmental resources and reduction of pollution, improved food safety, and a healthier diet. (Session and presentation at the UNFCCC- COP27 in Sharm el-Sheikh, Egypt)

3.3] Designing edible scaffolds and growing bovine 'whole cut' for the cultured meat

We aim to develop an innovative, cost-effective, and scalable approach for the production of bovine 'whole cut' cultured meat products. In addition, this multicellular 'whole cut' will have desired nutritional properties and support cellular proliferation and/or differentiation. Within the scope of the current research project, our primary goal is to produce a working prototype of one or more edible scaffolds and characterize their ability to support bovine mesenchymal stem cells proliferation and differentiation into muscle and fat tissues.

Cellular agriculture is an evolving branch of biotechnology that aims to improve traditional agriculture on issues related to environmental impacts, animal welfare and sustainability. One of the proposed solutions is cultured meat (CM) cultured meat - which does not yet exist in commercial production.

Cultured meat has flourished in recent years as the demand for CM products has risen. This is mainly due to the moral reluctance of a considerable percentage of the population from the breeding practices in the coops and farms as well as from the mass slaughter of livestock for meat. The awareness of emerging climate change increases the global demand for alternative protein sources.

Cultured meat (CM) is an emerging technology based on the proliferation and differentiation of animal stem cells in vitro to produce edible tissues for human consumption¹. First, a significant improvement is needed for the process to become cost-effective and reliable enough to bring it to production on a scale suitable for the food supply². Secondly, cultured meat is animal tissue grown outside the body, in vitro. In general, tissue growth requires three things:  (1) Source cells: stem cells of adult animals (removed by biopsy or extracted from excess tissue, e.g. placenta, umbilical cord, etc.) or embryonic stem cells. The cells must have the ability to differentiate to form mature muscle tissue. (2) Support: The cells should grow on a surface and adhere to it in order to create three-dimensional muscle tissue with a noticeable thickness. (3) Nutrition: Cells are grown in a medium containing essential amino acids and growth factors. Moreover, to produce tissue comparable to meat, muscle cells should be combined with other cells, such as fat cells, and the scaffold has to allow transportation of nutrients through a system similar to capillaries².

3.4] Cost-effective “Smart Scaffold” production for the cultivated meat (CM) industry application

With this research, we aim to develop an innovative approach in the field of tissue engineering. When mature, this technology will enable the cost-effective production of complex cultivated meat (CM) products that require multiple cell types to be organized in a preordered shape tissue (Figure 1.). Within the scope of the current research project, our main goal is to produce a working prototype of such “Smart Scaffold”. The Schlesinger lab has been growing and differentiating bovine umbilical cord MSC (BUC-MSC) and bovine adipose MSC (BAD-MSC) for almost three years. We have several lines of MSC that can be grown and differentiated into chondrocytes, osteocytes and adipocyte fates in the lab by standard protocols. We have shown that BUC-MSC are highly expandable since from 2cm of UC we get more than one million of cells, which double every 22-26 hours for more than 40 days and remain multipotent and ready to differentiate (Shimoni et al., 2020).  In addition to the high scalability of the cells, their maintenance in culture is relatively lowcost and simple, and cellular senescence (aging) can be delayed by adding antioxidants to their growth media.  Recently, we have examined and optimized two muscle differentiation protocols and were able to show efficient differentiation of BUC-MSC into muscle fibers. Additionally, we induce faster adipogenesis by pre-treatment with heat shock, therefore directing the cells toward fate commitment before seeding on Scaffold.