Blastocyst complementation generates exogenic pancreas in vivo in apancreatic cloned pigs

TLDR

Regenerative medicine aims to generate functional organs from pluripotent cells, and applying this to large mammals requires compensating for empty developmental niches. The study demonstrates that blastocyst complementation can be performed in pigs via somatic cell cloning. Transgenic cloning produced apancreatic pig embryos, which were then complemented with allogenic blastomeres to generate functioning pancreata in the empty niches. Functional pancreas and kidney were generated from PSCs in organ‑deficient mice, and similar complementation in cloned pig embryos produced functioning pancreata, demonstrating that missing organs can be generated from exogenous pluripotent cells and enabling future in vivo organ generation in large animals.

Abstract

In the field of regenerative medicine, one of the ultimate goals is to generate functioning organs from pluripotent cells, such as ES cells or induced pluripotent stem cells (PSCs). We have recently generated functional pancreas and kidney from PSCs in pancreatogenesis- or nephrogenesis-disabled mice, providing proof of principle for organogenesis from PSCs in an embryo unable to form a specific organ. Key when applying the principles of in vivo generation to human organs is compensation for an empty developmental niche in large nonrodent mammals. Here, we show that the blastocyst complementation system can be applied in the pig using somatic cell cloning technology. Transgenic approaches permitted generation of porcine somatic cell cloned embryos with an apancreatic phenotype. Complementation of these embryos with allogenic blastomeres then created functioning pancreata in the vacant niches. These results clearly indicate that a missing organ can be generated from exogenous cells when functionally normal pluripotent cells chimerize a cloned dysorganogenetic embryo. The feasibility of blastocyst complementation using cloned porcine embryos allows experimentation toward the in vivo generation of functional organs from xenogenic PSCs in large animals.