Stem Cells: A Renaissance in Human Biology Research

Abstract

The understanding of human biology and how it relates to that of other species represents an ancient quest. Limited access to human material, particularly during early development, has restricted researchers to only scratching the surface of this inherently challenging subject. Recent technological innovations, such as single cell "omics" and human stem cell derivation, have now greatly accelerated our ability to gain insights into uniquely human biology. The opportunities afforded to delve molecularly into scarce material and to model human embryogenesis and pathophysiological processes are leading to new insights of human development and are changing our understanding of disease and choice of therapy options.

Engineering multicellular systems: Using synthetic biology to control tissue self-organization

“…When tight control over stem cell differentiation is desired only limited meaningful complexity in cellular composition is possible. Alternatively, when a high degree of complexity in cellular composition is desired, as in the case of organoids, direct control of individual cell fates is sacrificed [1,14]. Taken together, two recent examples show a path towards reconciling this trade-off.…”

“…Concurrently, deepening biological knowledge of the principles relating to cellular differentiation have led to a greater understanding of the plasticity of cell fate via reprogramming [14] and to the development of protocols for in vitro organoid generation [15]. Many points of genetic control on cell differentiation have been identified and can be used as targets for the creation of synthetic circuits driving changes in cell fate.…”

Stemness in Cancer: Stem Cells, Cancer Stem Cells, and Their Microenvironment

“…Stem Cells (SCs) have the capacity to self-renew and give rise to progeny capable of differentiating into diverse cell types [13]. SCs cannot survive either outside their environment or in the absence of specific factors and cytokines [14, 15].…”

Patient-derived induced pluripotent stem cells in cancer research and precision oncology

“…Simple, heterotypic 2D or 3D culture systems that incorporate niche elements of the tumor microenvironment can also be developed through co-culture with primary autologous, allogeneic or iPSC-derived stromal cells. Organoid cultures consist of 3D structures that recapitulate aspects of the architecture of the tissue from which they were derived, and they can be initiated using differentiated cells, tissue-specific (or adult) stem and progenitor cells or human pluripotent stem cells (hPSCs, including ESCs and iPSCs) 118–120 . Organoids derived from primary resected tumors or biopsies have been recently reported 121–125 .…”