Rodent-human chimeras for disease modeling

Rodent-human chimeras for disease modeling

Stem cell-derived human cells maintained in short-term laboratory cultures are considered imperfect models of slowly progressive ailments, such as Alzheimer’s and Parkinson’s diseases, which are marked by the gradual buildup of cellular changes.

Researchers induced mouse, rat, and human pluripotent stem cells to generate neural crest cells (NCCs), a multipotent cell type that develops within the nascent epidermis of embryos and engenders melanin-producing skin cells.

The authors injected the NCCs into 8.5-day-old embryos growing in the uterus of albino mice, thus creating hybrids, including rodent–human chimeras. Regardless of the source, the NCCs slid under the developing mouse epidermis, migrated deep into the embryos, and generated functional pigment cells, as evidenced by offspring coat colors.

Compared with primary NCCs, however, those generated in vitro were less efficient at contributing to offspring pigmentation. Similarly, NCCs derived from induced pluripotent stem cells generated from skin cells of an African American donor influenced offspring coat color, albeit to a smaller extent than mouse NCCs.

Experiments using recipient mice carrying a mutation that hobbles melanocyte formation suggested that the reduced ability of human NCCs derived from stem cells to influence offspring pigmentation might be ascribed to competition from the hosts’ melanin-producing cells.

According to the authors, interspecies chimeras represent a powerful tool to study stem cell-derived, patient-specific cells in human diseases.