Virgin birth: engineered heart muscle from parthenogenetic stem cells

Abstract

Cardiac muscle restitution, or true regeneration, is an unmet need in the treatment of myocardial infarction (MI), prompting a decade of study with stem cells of many kinds. Among key obstacles to effective cardiac cell grafting are the cost of autologous stem cell-derived cardiomyocytes, the ethical implications of using embryonic stem cell (ESC) products, immunological barriers to allogeneic cells, functional maturation beyond just the correct lineage decision, and the lack of durable engraftment. In this issue of the JCI, Didié and colleagues show that cardiomyocytes made from parthenogenetic stem cells (PSCs) and deployed as engineered heart muscle (EHM) may overcome all of these formidable barriers.

Figure 1. EHM from PSC-derived cardiomyocytes.

(Above) PSCs and ESCs are produced from oocytes arrested in meiosis II and stimulated to form a zygote, either by fertilization by sperm (ESC) or artificially with strontium chloride (PSC). In the production of ECSs, a polar body containing one set of the maternal genome is subsequently extruded as a polar body, whereas in PSC production this is prevented by cytochalasin B. Both processes result in 2 copies of the genome, although in the case of PSCs both are from the mother. PSCs, being uniparental in origin, are advantageous for immunological matching. From this stage onward, the production of stem cells from the parthenote follows that from embryos. The ICM of the blastocyst is removed and plated on mouse embryonic fibroblasts (MEFs), outgrowths are isolated, and embryoid bodies are grown in hanging drops. Undifferentiated or differentiated cells are then used for analysis in vitro and in vivo. (Below) Stem cells having made the lineage decision to become cardiomyocytes are induced to undergo functional maturation by a tissue-engineering approach including static mechanical stretch and inclusion of nonmyocytes. The use of EHM also promotes persistent engraftment after MI.