Anthony L. Komaroff, MD

Growing complex “replacement” human organs seems feasible.

Pluripotent human stem cells — whether embryonic stem cells or induced pluripotent stem cells (iPSCs) — can replace cells that have been killed by disease. An example is replacement of myocardial cells that have been killed by infarction. However, using stem cells to create whole organs is a much bigger challenge: A whole organ has many different cell types and requires a vascular and nerve supply to function.

A multicenter team seeded a cylindrical structure with either human embryonic stem cells or human iPSCs and exposed the cells to growth factors that encourage development of intestine. During 35 days, small cylinders of intestinal epithelium and mesenchyme formed. These tiny “human intestinal organoids” (HIOs) were implanted into kidney capsules of immunocompromised mice. During the next 6 weeks, the HIOs grew 50- to 100-fold larger, with crypt-villus architecture and underlying laminated submucosal layers — all of human cell origin. The HIOs made brush-border digestive enzymes and were capable of absorbing gut contents (surgically placed into the ectopic HIOs) into the bloodstream. Blood supplies for the HIOs developed in the mice, and the HIOs were responsive to systemic signals.

Citation(s):

Watson CL et al. An in vivo model of human small intestine using pluripotent stem cells. Nat Med 2014 Nov; 20:1310.