Stem Cell Systems Bioengineering uses engineering principles to advance the knowledge of biological systems, and ultimately contribute to the translation of new therapeutic approaches to clinical practice. Key technologies include novel bioprocesses for the maintenance and expansion of human stem cells, as well as their differentiated progeny, and micro/nanofabrication to produce tissue-like substitutes. Other emergent topics include the development of cellular products based on innovative 3D cultivation systems, e.g. organoids, functional human tissue-like substitutes, controlled-release particles to program cellular responses, novel bioprinting to generate tissues, and the use of artificial intelligence to model such systems. Furthermore, the development of in vitro tests for toxicity, cell differentiation, genomic stability of expanded cells and biocompatibility can profit from these scientific and technological advancements. Finally, these technologies should be translated and implemented under Good Manufacturing Practice (GMP) conditions, in order to facilitate their clinical application.

Advances in the bioengineering field have allowed the manipulation of singular aspects of the cellular microenvironment, and this Research Topic aims to focus on outstanding examples of bioengineering approaches used to promote the self-organization of human cells and the production of tissue-like structure formation. Also crucial to this endeavor is the understanding of the biological system in hand, and special attention will also be given to methodologies that help advance the comprehension of the mechanisms that control stem cell activity. Moreover, to truly become ground-breaking, such advancements should eventually be translated to the clinic. For that, scalable processes for the maintenance and expansion of transplantable human cells are of special interest, particularly novel 3D organoid systems and devices for the production of functional tissue-like substitutes.

This Research Topic aims to attract original contributions related to human stem cell systems, namely embryonic and induced pluripotent stem cells, hematopoietic stem/progenitor cells, mesenchymal stem cells, and endothelial progenitor cells. Review articles describing the current state-of-the-art are also encouraged and welcomed. Special focus will be given to contributions covering:

• Methods to advance basic understanding of the mechanisms that control stem cell activity and their differentiation, including novel computational approaches using artificial intelligence (Systems Biology and Engineering);
• Advanced materials to improve cell functionality and physiological responses of engineered cellular constructs, including the development of novel bioinks to enable 3D printing of stem cells (Niche Engineering);
• Controlled-release systems to guide cell responses (Niche Engineering);
• Technologies for derivation and isolation of stem cells from diverse sources (Bioprocessing);
• Scalable processes for the maintenance and expansion of transplantable human cells, ensuring their availability for cell-based therapies (Bioprocessing);
• Engineering of 3D organoid systems and production of functional human tissue-like substitutes (Cell and Tissue Engineering).

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Dr. Stephanie Willerth has a commercialization agreement with Aspect Biosystems with regards to bioprinting stem cell derived tissues. Dr. Yuguo Lei is a co-founder of CellGro Technologies, LLC, a company focusing on cell expansion technologies. Dr. Tiago Fernandes has no competing interests with regards to this Research Topic.

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