Development and application of human adult stem or progenitor cell organoids

Abstract

Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for several other organs and translated to humans. Organoid cultures have proved valuable for basic research and for the study of healthy tissue homeostasis and the biology of disease. In addition, data from proof-of-principle experiments support promising clinical applications of adult stem or progenitor cell organoids. Although renal organoids have many potential applications, an adult stem or progenitor cell organoid culture system has not yet been developed for the kidney. The development of such a system is likely to be challenging because of the intricate renal architecture. Differentiated 3D cultures and stem or progenitor cell 3D sphere cultures are, however, available for the kidney. These cultures indicate the feasibility of renal organoid culture and provide a solid basis for its development. In this Review, we discuss the state-of-the-art of human adult stem or progenitor cell organoid culture and the potential of renal organoids as tools in basic and clinical research.

A bioengineered niche promotes in vivo engraftment and maturation of pluripotent stem cell derived human lung organoids

“…These advances stem from our ability to culture primary human tissues and derive complex three-dimensional organ-like tissues, called organoids from human pluripotent stem cells (hPSCs) (Dedhia et al, 2016; Fatehullah et al, 2016; Johnson and Hockemeyer, 2015; Huch and Koo, 2015; Rookmaaker et al, 2015; Dye et al, 2016). Both tissue-derived and hPSC-derived human lung models have been developed and recapitulate some structural and cellular features of the human lung (Barkauskas et al, 2013; Rock et al, 2009; Gotoh et al., 2014; Konishi et al, 2016; Vaughan et al, 2006; Pageau et al, 2011; Fessart et al, 2013; Franzdóttir et al, 2010; Kaisani et al, 2014; Dye et al, 2015; Firth et al, 2014; Mou et al, 2016).…”

Generation of an artificial intestine for the management of short bowel syndrome

“…There has been tremendous progress in the identification of signature molecules that define the intestinal stem cell, and in the development of techniques that permit the maintenance of intestinal stem cells in tissue culture see [8,14,15] for recent review, see representative image of cultured human intestinal stem cells from our lab in Figure 2 . While a full description of each of the studies regarding the characterization of the intestinal stem cell is beyond the scope of the current work, the reader is referred to recent reviews by Barker and Rookmaaker et al, which provide a more complete description [13,15].…”

“…While a full description of each of the studies regarding the characterization of the intestinal stem cell is beyond the scope of the current work, the reader is referred to recent reviews by Barker and Rookmaaker et al, which provide a more complete description [13,15]. Perhaps the most important recent advance in the identification and isolation of molecules that define the intestinal stem cell involves the work of Hans Clevers and colleagues [10,15], who defined the expression of the wingless (Wnt) target gene leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) as a signature feature of the intestinal stem cell within the intestinal crypts [10]. Lgr5 is a receptor for the chemokine r-spondin, which is a key regulator of the Wnt/β-catenin signaling pathway within the intestine [16].…”

Organoid Models of Human Gastrointestinal Development and Disease

“…Many research articles and reviews have highlighted the use of organoid systems to characterize the adult stem cell niche and gut morphogenesis, and will not be covered in detail in this review (see 1, 3, 40–43, 56, 58, 59, 70, 86–95 ). We aim to define and discuss the variety of long-term in vitro GI models that have been created, and how they have increased our understanding of development, genetic diseases of the GI tract, malignancy, host–pathogen interactions, tissue reprogramming, and regeneration.…”