Embryonic Stem Cell Contamination Responsible for STAP Research Snafu

STAP or stimulus-triggered acquisition of pluripotency cells were allegedly derived from mature, adult cells by simply subjecting those cells to environmental stresses. These environmental stresses, such as low pH treatments and so on, were thought to cause cells to express genes that pushed them into an embryonic stem cell-like state. Researchers from the RIKEN institute reported these reports in the prestigious international journal Nature, and these advances were hailed as a stupendous advancement in stem cell biology.

However, as soon as stem cell scientists tried to repeat the results from these papers and failed, trouble started. Major laboratories had no success in recapitulating the results in the RIKEN institute papers, and, on-line post-publication reviews noticed some nagging problems in the published papers. RIKEN institute launched an investigation into the matter, and concluded that the lead researcher in these papers was guilty of scientific misconduct.

Now, new work as suggested that the whole thing was the result of contamination of the RIKEN group cells with embryonic stem cells. How that contamination occurred, however, remains unknown.

The RIKEN institute investigation was instigated by the institute and was carried out by a committee composed of seven outsiders. The committee analyzed DNA samples and laboratory records from two research teams who had participated in the STAP cell research. Those Nature papers have been retracted, but were once thought to provide a shortcut to producing pluripotent stem cells. The latest investigation suggests that the STAP findings resulted from contamination by embryonic stem cells. The investigation found signs of three separate embryonic stem cell lines, and they noted that it is difficult to imagine how contamination by three distinct lines could be accidental, but that they could also not be certain that it was intentional.

“We cannot, therefore, conclude that there was research misconduct in this instance,” the committee wrote. It did, however, find evidence that lead investigator Haruko Obokata, the lead author of the STAP papers, who formerly worked at the RIKEN Center for Developmental Biology in Kobe, Japan, had fabricated data for two figures in the original STAP publications.

Children’s Hospital Los Angeles Researchers Grow Functional Tissue-Engineered Intestine from Human Cells

Children’s Hospital Los Angeles is the home of a remarkable new study that has succeeded in growing tissue-engineered small intestine from human cells. This tissue engineered intestine recapitulates several key functional characteristics of human intestine such as the ability to absorb sugars. It also has structural features of human small intestine, such as a mucosal lining, support structures tiny and ultra-structural components like cellular connections.

This work was published in the American Journal of Physiology; GI and Liver and brings surgeons one step closer to using tissue engineered intestines in human patients.

Tissue-engineered small intestines are grown from stem cells isolated from the intestine. These laboratory-grown tissues offer a promising treatment for clinical conditions such as short-bowel syndrome (SBS), which is a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue engineered small intestines may also, perhaps in the future, offer a therapeutic alternative to intestinal transplantations, which is fraught with the problems of donor shortage and the need for lifelong immunosuppression.

Senior author Dr. Tracy Grikscheit, who is a principal investigator at the Saban Research Institute, which is housed at the Children’s Hospital of Los Angeles (CHLA), and the Developmental Biology and Regenerative Medicine program at the Children’s Hospital of Los Angeles. Dr. Grikscheit is also a pediatric surgeon at CHLA and assistant professor of surgery at the Keck School of Medicine of the University of Southern California.

Grikscheit main interest, as a clinician, is to find strategies to treat the most vulnerable young patients. For example, babies who are born prematurely can sometimes develop a devastating disease called necrotizing enterocolitis (NEC), in which life-threatening intestinal damage demands that large portions of the small intestine be surgically removed. Without a long enough intestine, NEC babies are dependent on intravenous feeding. This intravenous feeding is costly and may cause liver damage. NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing and nearly a third of patients die within five years.

CHLA scientists had previously shown that tissue-engineered small intestine could be generated from human small intestine donor tissue implanted into immunocompromised mice. These initial studies were published in July 2011 in the biomedical journal Tissue Engineering, Part A, and while it was a hopeful study, only basic components of the intestine were identified in the implanted intestine. To be clinically relevant, it is necessary to make tissue engineered intestines that form a healthy barrier that can still absorb nutrition and regulate the exchange of electrolytes.

This new study, however, showed that mouse tissue engineered small intestines are quite similar to the tissue-engineered small intestines made from human intestinal stem cells. Both contain important building blocks such as the stem and progenitor cells that continue to regenerate the intestine throughout the lie of the organism. These cells are found within the engineered tissue in specific locations and are close to other specialized cells that are known to be necessary for the intestine to function as a fully functioning organ.

“We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,” said Grikscheit. “Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure.”