Ajna Bihorac

In 100 and plus years of stem cell research, scientists are trying to define all the types of stem cells, their markers, differentiation abilities, and possibilities that those cells hold [1]. Induced pluripotent stem cells (iPSCS) are "human-made", induced stem cells that can be produced from different donors and cell types. They have shown to own multiple advantages compared to "natural" stem cells, such as embryonic stem cells (ESCs), adult stem cells, and fetal stem cells. iPSCs were induced by reprogramming of somatic cells, mouse embryonic fibroblasts (MEFs) in 2006, by Takahasi and Yamanaka [2]. The new era started after that, and it is still ongoing. Defining usage of different cells, the best donors, then states of cells during iPSCs reprogramming, and the markers that define them may pave the way for easier reprogramming, thus the focus of research may be on the possibilities that iPSCs hold in regenerative medicine [3], preservation of vulnerable and endangered species [4], drug discovery and testing, disease modeling [3] and cell therapy. One of the ways that can make the path easier, is tools that would collect data, analyze data and give the approximation of the solution. Artificial intelligence which applies machine learning, deep learning and other techniques, may be a valuable factor in producing models and comparing in effectiveness during the reprogramming. Human factor provides data, while artificial intelligence-based methods can bring improvement in accuracy, costs and speed of data analysis [5].

The European wisent (Bison bonasus), an iconic yet genetically vulnerable species, faces ongoing conservation challenges due to a restricted gene pool. Advances in induced pluripotent stem cell (iPSC) technology offer promising prospects for preserving and restoring genetic diversity in endangered species. In this study, we sought to reprogram wisent somatic cells into iPSCs using the PiggyBac transposon system, a non-viral method known for being successfully applied in bovine species. We applied a six-factor reprogramming cocktail (OCT4, SOX2, KLF4, LIN28, c-MYC, NANOG) alongside small-molecule enhancers to fibroblasts isolated from adult wisent tissue. While initial colony formation was observed, the reprogrammed cells exhibited limited proliferation and failed to maintain stable pluripotency, suggesting intrinsic barriers to complete reprogramming. Despite optimizing culture conditions, including hypoxia and extracellular matrix modifications, the reprogramming efficiency remained low. Our findings indicate that wisent somatic cells may require alternative reprogramming strategies, such as new-generation delivery systems and epigenetic modulators, to achieve stable iPSC lines. This study underscores the need for species-specific optimization of reprogramming protocols and highlights the potential of emerging cellular technologies for conservation efforts. Future research integrating advanced reprogramming tools may pave the way for genetic rescue strategies in wisent and other endangered species.

A search for the “magic bullet”, a molecule, the targeting abilities of which could stop the migration of tumor cells, is currently underway, but remains in the early stages. There are still many unknowns regarding the cell migration. The main approach is the employment of mouse models, that are sources of valuable information, but still cannot answer all of the questions. One of the molecules of interest is Transglutaminase 2 (TG2). It is a well-described molecule involved in numerous pathways and elevated in metastatic tumors. The question remains whether mice and humans can give the same answer considering TG2.