Stem Cells Made from the Brains of Cadavers

Shinya Yamanaka won the Nobel Prize this year for his discovery that the application of genetic engineering to adult cells can revert them into embryonic-like stem cells. Such cells, known as induced pluripotent stem cells (iPSCs) are made from adult cells when four different genes are transiently expressed in an adult cell. These four particular genes are all transcription factors that bind to DNA and activate the transcription of particular genes that are necessary for the acquisition of the embryonic state. Once they are derived, iPSCs can grow in culture and differentiate into any adult cell type, although the efficiency with which they do this is very cell line-dependent.

The discovery of iPSCs gave new hope to the notion that patient-specific stem cells could be used to treat genetic diseases. However, a research group has actually managed to extract live cells from dead bodies and use those cells to derive iPSC lines.

Fibroblasts are cells found in connective tissue, and they are very common in the skin and brain. Fibroblasts can be collected from cadavers and subjected to a protocol that will convert them into iPSCs. These reprogrammed stem cells can differentiate into a multitude of cell types, including the neurons found in the brain and spinal cord. Because microorganisms can colonize the body and degrade it after death, such a culturing process is tricky to carry out successfully.

Scientists from the laboratory of Thomas Hyde at the Lieber Institute for Brain Development, Johns Hopkins Medical Campus in Baltimore, Maryland have used fibroblasts from scalps and the linings that surround the brain (dura later) from 146 human brain donors and used them lake iPSCs.

Those cells extracted from the dura mater were 16 times more likely to grow successfully than those from the scalp. Hyde explained that he expected this disparity in growth potential since the scalp is prone contamination with bacterial and fungi after death. Such contaminants can inhibit the growth of fibroblasts in the laboratory.

However, scalp cells grew more rapidly than dura mater cells. “Since the skin is constantly renewing, while the turnover in dura mater is much slower,” such a result makes sense, explained Hyde.

The derivation of iPSCs from cadavers might play an important role in developing future stem cell therapies. Cadavers can provide brain, heart and other tissues for study that researchers cannot safely obtain from living people. The derivation of iPSCs from cadavers provides scientists with an excellent source of material for research that cannot be obtained elsewhere. As noted in the paper, “These tissues may be accessible through existing brain tissue collections, which is critical for studying disorders such as neuropsychiatric diseases.”

“For instance, we can compare neurons derived from fibroblasts with actual neurons from the same individual,” Hyde said. “It tells us about how reliable a given method for deriving neurons from fibroblasts is. That can be crucial if, for example, you want to create dopamine-making neurons to treat someone with Parkinson’s disease.”

Also using iPSCs made from patients who died from developmental abnormalities can greatly enlighten scientists on those maladies that are due to malfunctions in development.

“We’re very interested in major neuropsychiatric disorders such as schizophrenia, bipolar disease, autism and mental retardation,” Hyde said. “By understanding what goes wrong with the brain cells in these individuals, we could perhaps help fix that.”

Citation: Bliss LA, Sams MR, Deep-Soboslay A, Ren-Patterson R, Jaffe AE, et al. (2012) Use of Postmortem Human Dura Mater and Scalp for Deriving Human Fibroblast Cultures. PLoS ONE 7(9): e45282. doi:10.1371/journal.pone.0045282