Frontiers in Stem Cell and Regenerative Medicine Research

Embryology is a part of anatomical sciences investigating formation, differentiation, growth and development of embryos and fetuses. This science is not only limited to the definition above, but it can also be used for human adults involved in perinatology, infertility, congenital defects, cell therapy and personalized medicine. This chapter aims to introduce embryology and its role in the clinical practice of physicians. The linkage of embryology and medicine is an example of the linkage between basic and clinical medical sciences. Entering to this interdisciplinary field opens a novel door for making hypotheses for future studies. 

Every human is a result of a cell formed from the fertilization of an oocyte with a sperm. This cell is called a zygote. A miracle is how just one cell can make a lot of tissues and organs. Regulation of gene expression is the first step of tissue development. Regulation of gene expression has different levels, including the genome (DNA content), transcriptome (RNA content, resulted from the transcription of DNA), and proteome (protein content, resulted from the translation of RNA) levels. The final consequence of gene expression regulation is cellular phenotype. The resulted proteins act for inter-cellular signaling transduction and tissue development. We aimed to show the details of gene expression regulation, cellular signaling transduction and interaction, and tissue development. We have shown a scheme of the gene to fetus formation. 

Cellular differentiation is a biological process in which a cell permanently alters its characteristics (phenotype), ensuring that its descendants also inherit these traits or can modify them when subjected to other differentiating stimuli. During this process, genetic changes occur within cells, leading to a commitment to a specific cell fate. Totipotent cells (stem cells) undergo differentiation based on their ultimate cell destiny, dictated by the tissue they will eventually become a part of it. A current challenge in regenerative medicine involves employing biomaterials within hydrogel matrices to induce changes in cell phenotype and functionality. Stem cells from various sources can thrive within 3D biomatrices featuring defined chemical compositions, and depending on the physical, chemical, and biological cues encountered, they can assume diverse phenotypes. The utilization of hydrogels composed of natural and synthetic polymers, as well as inorganic components, has been explored for such purposes, revealing a direct correlation between the structure and physicochemical properties of polymeric matrices and their impact on cell differentiation capacity. Consequently, the encapsulation of stem cells within these biomaterials can be tailored to enhance the effectiveness of regenerative medicine treatments, particularly in the regeneration of cardiac, dermal, epithelial, cartilaginous, and nervous tissues. This chapter aims to elucidate the fundamental principles of cellular differentiation in stem cells facilitated by biomaterial compositions within hydrogel matrices and explore its potential applications in regenerative medicine.

Sepsis is a life-threatening syndrome that develops as a result of a dysregulated immune response caused by an infectious agent. The pathogenesis of sepsis has been better understood over the years, and new treatment protocols have been developed. In sepsis, the host immune response is equally as important as the infectious agent in the clinical presentation of sepsis and the development of shock. In the early phase of sepsis, hyperinflammation and secondary hyperinflammation occur, while in the late phase, immunosuppression is present. Sepsis treatment is based on controlling the source of infection, antimicrobial treatment and supportive treatment depending on the phase of sepsis. 

Stem cells have shown great potential in recent years to become a new therapeutic option for infectious diseases. The stem cell is an undifferentiated cell that can selfrenew to proliferate and differentiate into specialized cells under appropriate conditions. The following section focuses on stem cell therapy, which is an adjuvant treatment method in the treatment of sepsis. Mesenchymal stem cells (MSCs) have immunomodulatory properties through direct or paracrine interactions with immune cells involved in innate or adaptive immunity. In the treatment of sepsis, MSCs have shown promise in reducing mortality and bacteremia in experimental mouse models of sepsis. However, the number of completed clinical trials on sepsis is very limited. These studies have shown the use of MSCs to be safe at appropriate doses. Nevertheless, there may be a risk of thromboembolic events following high-dose applications. There remains a need for clinical studies on timing, dose and duration of use. 

 Stem cells hold a great promise for regenerative medicine given their ability to proliferate and differentiate into various cell types. However, self-renewal and multipotency also grant a high capacity to form tumor tissues in vivo post-therapeutic administration. Indeed, multiple case reports have revealed the formation of stem cell derived tumors, such as teratoma, in animal models and even in clinical applications. As a result, examination of tumorigenicity becomes one of the major considerations when assessing the safety of stem cell-derived therapeutic products. Ideally, the assessment needs to be performed in a rapid, sensitive, cost-effective, and scalable manner. In this chapter, the current practices of assay development to fulfill this demand are reviewed. Progress in animal models, soft agar culture, PCR, flow cytometry, and microfluidics are introduced and compared comprehensively. Some insights regarding the assay selection and future development are also provided as there is no one-for-all assay at this moment.