PubMed · 14862695
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F DOMINGUEZ. 1951. [Typhoid perforations].. https://pubmed.ncbi.nlm.nih.gov/14862695/
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Three-dimensional organoids of the gut, liver, and lung have become mainstream models of human development, disease, and therapy. These organs share an embryonic endodermal origin, yet the field measures their progress inconsistently because the word "maturity" carries two unrelated meanings. Herein, we review the organoid work across all three organs and propose that the two orthogonal axes of advancement be analyzed separately. The first axis is single-organ fidelity. Adult stem cell organoids are faithful but partial, reproducing the adult epithelium of their source tissue with genomic stability yet lacking stromal, vascular, immune, and neural compartments. Human pluripotent stem cell organoids are complete but immature, co-emerging with multiple lineages yet arrested in a fetal-like state. The cost of each limitation is organ-dependent, smallest in the intestine, largest for hepatic drug metabolism, and most spatially defined across the proximal and distal lungs. The second axis is inter-organ reconstruction, where progress is strongly asymmetric. The gut-liver axis is comparatively advanced and sustained by linked organoid and microphysiological systems. The gut-lung axis, by contrast, remains the least-developed frontier, and no such linked organoid has yet been built. We therefore frame it as a proposal, using in vivo and correlative evidence to outline the design principles for such a model. Four bottlenecks recur across both axes: limited vascularization; batch-to-batch variability; organ-skewed immune, microbial, and stromal microenvironments; and unidirectional signaling. We argue that benchmarking models against single-cell developmental atlases and prioritizing construction of the gut-lung frontier should guide the field over the next decade.
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The geometry of intact and detubularized intestinal segments is examined to establish guidelines for estimating the length of bowel required for urinary reconstruction. Because a sphere has the highest ratio of volume to surface area of any geometric form, whenever bowel is detubularized the resulting spherical reservoir will always hold a larger volume than the original cylinder, but unfortunately there is no simplistic formula to estimate this gain. Therefore, tables are presented which calculate the resulting volumes and the gain in volume of detubularized spherically shaped reservoirs used for bladder augmentation and substitution. These tables demonstrate the striking gain in volume that results from detubularizing bowel and provide guidelines for determining the length of bowel segments required for different types of urinary tract reconstruction.