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Mouse and human postnatal and fetal organoid units (OUs) maintained in either short-term culture (2 weeks) or long-term culture (from 4 weeks up to 3 months) without adding exogenous growth factors were implanted in immunocompromised mice to form tissue-engineered small intestine (TESI) in vivo. Intestinal epithelial stem and neuronal progenitor cells were maintained in long-term OU cultures from both humans and mice without exogenous growth factors, and these cultures were successfully used to form TESI. This was enhanced with OUs derived from human fetal tissues. Organoid unit culture is different from enteroid culture, which is limited to epithelial cell growth and requires supplementation with R-Spondin, noggin and epidermal growth factor. Organoid units contain multiple cell types, including epithelial, mesenchymal and enteric nervous system cells. Short- and long-term cultured OUs derived from mouse and human intestine develop into TESI in vivo, which contains key components of the small intestine similar to native intestine.

Liver disease affects large numbers of patients, yet there are limited treatments available to replace absent or ineffective cellular function of this crucial organ. Donor scarcity and the necessity for immunosuppression limit one effective therapy, orthotopic liver transplantation. But in some conditions such as inborn errors of metabolism or transient states of liver insufficiency, patients may be salvaged by providing partial quantities of functional liver tissue. After transplanting multicellular liver organoid units composed of a heterogeneous cellular population that includes adult stem and progenitor cells, both mouse and human tissue‐engineered liver (TELi) form in vivo. TELi contains normal liver components such as hepatocytes with albumin expression, CK19‐expressing bile ducts and vascular structures with α‐smooth muscle actin expression, desmin‐expressing stellate cells, and CD31‐expressing endothelial cells. At 4 weeks, TELi contains proliferating albumin‐expressing cells and identification of β2‐microglobulin‐expressing cells demonstrates that the majority of human TELi is composed of transplanted human cells. Human albumin is detected in the host mouse serum, indicating in vivo secretory function. Liquid chromatography/mass spectrometric analysis of mouse serum after debrisoquine administration is followed by a significant increase in the level of the human metabolite, 4‐OH‐debrisoquine, which supports the metabolic and xenobiotic capability of human TELi in vivo. Implanted TELi grew in a mouse model of inducible liver failure. Stem Cells Translational Medicine 2017;6:238–248