Prockop's group stumbled across this remarkable ability while studying bone marrow stem cells (MSCs), which were particularly social in culture, often touching each other and then backing off. Small numbers of MSCs can repair some damaged heart cells, whose main defect is usually a loss of mitochondrial activity. The authors thus wondered whether the contact behavior allowed MSCs to transfer mitochondria. “It was a way out-there hypothesis,” says Prockop, “that we wouldn't have mentioned to anyone had the experiment not worked out.”
To test their “out-there” idea, the group damaged the mitochondrial genome (mtDNA) of a transformed epithelial cell line using ethidium bromide and then looked for rescue by MSCs. Indeed, rescued clones appeared that contained MSC-derived mitochondrial proteins. Fibroblasts were also able to rescue the damaged cells. It is unclear whether healthy cells take in mitochondria as well.
After ruling out cell fusion as an explanation, the group hoped to show the transfer directly. But a dearth of fluorescent mtDNA tags has made the transfer hard to follow. Cultured cells did not take in isolated, cell-free mitochondria, so donation appears to be an active process.
Perhaps the organelles are passed through the recently recognized structures called nanotubes. Or they might be sent out by exocytosis. The group saw that MSCs leave behind mitochondria-filled vesicles that end up attached to other cells, but they have not seen these vesicle internalized as yet. For now, given the therapeutic implications for mitochondrial diseases, the group hopes to prove that transfer occurs in vivo.