PITTSBURGH, Aug. 5 -- Routinely discarded as medical waste, placentaltissue could feasibly provide an abundant source of cells with the samepotential to treat diseases and regenerate tissues as their morecontroversial counterparts, embryonic stem cells, suggests a Universityof Pittsburgh study to be published in the journal Stem Cells andavailable now as an early online publication in Stem Cells Express.
A part of the placenta called the amnion, or the outer membrane ofthe amniotic sac, is comprised of cells that have strikingly similarcharacteristics to embryonic stem cells, including the ability toexpress two key genes that give embryonic stem cells their uniquecapability for developing into any kind of specialized cell, theresearchers report. And according to the results of their studies,these so-called amniotic epithelial cells could in fact be directed toform liver, pancreas, heart and nerve cells under the right laboratoryconditions.
"If we could develop efficient methods that would allowamnion-derived cells to differentiate into specific cell types, thenplacentas would no longer be relegated to the trashcan. Instead, we'dhave a useful source of cells for transplantation and regenerativemedicine," said senior author Stephen C. Strom, Ph.D., associateprofessor of pathology at the University of Pittsburgh School ofMedicine and a researcher at the university's McGowan Institute forRegenerative Medicine.
According to U.S. census figures, there are more than 4 millionlive births each year. For each discarded placenta, the researcherscalculate there are about 300 million amniotic epithelial cells thatpotentially could be expanded to between 10 and 60 billion cellsrelatively easily.
"Provided that research advances to the point that we candemonstrate these cells' true therapeutic benefit, parents couldconceivably choose to bank their child's amniotic epithelial cells inthe event they may someday be needed, as is sometimes done now withumbilical cord blood," commented Dr. Strom.
The amnion is derived from the embryo and forms as early aseight days after fertilization, when the fate of cells has yet to bedetermined, and serves to protect the developing fetus. According tothe researchers' studies using placentas from full-term pregnancies,amniotic epithelial cells have many of the telltale surface markersthat define embryonic stem cells, and also express the Oct-4 and nanoggenes that are known to be required for self-renewal and pluripotency-- the ability to develop into any type of cell.
Yet the authors are careful to point out that despite theirremarkable similarities to embryonic stem cells, amniotic epithelialcells are not stem cells per se, because they can't grow indefinitely.This may be due to the fact that these amnion-derived cells do notexpress a certain enzyme, called telomerase, that is important fornormal DNA and chromosome replication, and by extension, ultimately,cell division.
"Perhaps it's to their advantage that the amnion epithelialcells lack telomerase expression, because telomerase is associated withmany cancers and one of the main concerns about stem cell therapies isthat transplanted stem cells would replicate in the recipient to formtumors," noted Toshio Miki, M.D., Ph.D., first author of the paper andan instructor in the department of pathology at the School of Medicine.
To help determine if amnion-derived cells that are delivereddirectly to tissues would cause tumors, the researchers conductedstudies in immune system-deficient mice and found no evidence thattumors had developed seven months after the cells were injected intomultiple sites.
While amniotic epithelial cells do not share the same capacityfor unlimited replication as do embryonic stem cells, they still candouble in population size about 20 times over without needing anothercell type serving as a feeder cell layer. This is significant, becauseto replicate, the currently available embryonic stem cell lines requirea bed of mouse cells, traces of which can end up in each new generationof stem cells. Amniotic epithelial cells, on the other hand, createtheir own feeder layer, with some cells choosing to spread out at thebottom of the culture dish thereby giving those cells just above themthe best environment for replicating and for retaining their stem cellcharacteristics.
With the addition of various growth factors, the authors reportthe amnion-derived cells could differentiate to become liver cells,heart cells, the glial and neuronal cells that make up the nervoussystem, and pancreatic cells with genetic markers for insulin andglycogen production.
"In this first paper we sought to determine if amnioticepithelial cells have the potential to differentiate into manydifferent cell types rather than focusing on ways for optimizing thispotential for a specific cell type. Further studies will be required tobetter understand if and how they may be useful in a clinical setting,"Dr. Strom added.
The researchers say their original motivation was, and stillis, to identify cells with the same therapeutic promise as embryonicstem cells. To this end, they began looking at the viability of amnionas a cell source in late 2001, obtaining discarded placentas fromfull-term births under an Institutional Review Board-approved protocol.In 2002, the University of Pittsburgh licensed the technology to acompany now called Stemnion, LLC, and as part of the agreement, and inkeeping with university patent policy, Drs. Strom and Miki will receivelicense proceeds. Both have served as paid consultants and hold equityin Stemnion.
The research was supported by the Alpha-1 Foundation and theNational Institute of Diabetes and Digestive and Kidney Diseases, apart of the National Institutes of Health. In addition to Drs. Miki andStrom, other authors are Thomas Lehmann, Ph.D., and Hongbo Cai, M.D.,Ph.D., both from the department of pathology, and Donna Stolz, Ph.D.,of the department of cell biology and physiology.
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