New Way to Improve Stem Cell Production May Improve IPF Treatment

North Carolina State University researcher have tested a faster, cheaper way to harvest and grow lung stem cells that have been extracted from patients’ own bodies. That makes such cells a perfect match for lung patients, according to a small proof-of-concept trial.

Ke Cheng, an associate professor of regenerative medicine at NC State, and his team tested this method with, a view toward eventually treating people with idiopathic pulmonary fibrosis, or IPF, a disease that causes inflammation in lung tissue that over time becomes thick and stiff. This scarring of tissue negatively affects lung function over time.

“In current stem cell harvesting, just the process of sorting the stem cells can damage them, wasting not only the cells, but also time and money,” said Cheng. “We wanted to see if we could take healthy stem cells from an organ while they were still in a supportive environment, recreate and enhance that environment outside the body to encourage stem cell reproduction, then reintroduce those cells into a damaged organ to treat disease.”

Cheng and others placed healthy, human adult lung stem cells in a multicellular spheroid, a three-dimensional structure with stem cells in the middle surrounded by layers of support cells. Spheroids are typically used in the laboratory to culture cancer or embryonic cells.

They then used mice with IPF and injected cultured human stem cells into the animals. These injected stem cells produced decreases in inflammation and fibrosis, which Cheng said matched the condition of lungs in the study’s control group that did not have IPF.

Cheng hopes that stem cells isolated from biopsies in human patients can be used to grow and harvest additional cells. Such a procedure should be able to decrease the number of invasive procedures necessary for treatment.

“Picture the lung as a garden and the stem cells as seeds,” Cheng said. “In an IPF environment, with inflammation, the soil is bad, but the seeds are still there. We take the seeds out and give them a protected place to grow. Then when we put them back into the lung, they can grow into mature lung cells to replace the damaged lung tissues in IPF. They can also wake the other seeds up, telling them to help fight the inflammation and ‘improving’ the soil.”

The study was published in the journal STEM CELLS Translational Medicine.

Artificial Tracheal Researcher Cleared of Misconduct Charges

Karolinska Institutet researcher Paolo Macchiarini has been cleared of misconduct charges after what was described as a “a detailed and lengthy investigation,”

The investigation of Dr. Macchiarini was based on his work that was published in seven papers that described the successful transplantation of bioengineered tracheas into patients with tracheal defects. These tracheas were reportedly made from the patient’s own stem cells. The complaints against Macchiarini were lodged by four physicians at Karolinska University Hospital; all of whom were part of the research environment and, in some cases, were even co-authors of the articles in question.

The complainants charged that the findings reported in the first six papers did not agree with the medical records of the patients who were treated. Additionally, there was also a problem with the seventh paper, which describes the implantation of a synthetic esophagus into a rat and a subsequent computed-tomography scan to verify its function. The initial investigation claimed, among other things, that Dr. Macchiarini “selectively described” certain minor problems in the patients while omitting serious complications.

These complaints were submitted in June, August and September 2014, and they prompted an inquiry by Karolinska Institutet’s vice-chancellor in accordance with the provisions of the Higher Education Ordinance and the university’s own established rules for dealing with cases of alleged scientific misconduct.

The recent decision by the university, announced Aug. 28, overturned the decision of an independent investigator commissioned by Karolinska. Bengt Gerdin. Dr. Gerdin is a general surgeon and professor emeritus at Uppsala University in Sweden, and he had concluded in May that Dr. Macchiarini committed misconduct, saying there were problems with those papers that described the transplant procedure in humans. Specifically, there was no evidence for the dramatic improvement claimed in a 2011 Lancet paper concerning such things as blood-vessel formation that penetrated into the grafted trachea.

In response to that investigation, in June the Swedish Research Council announced a freeze on grant payouts to ACTREM (the Centre for Regenerative Medicine) at Karolinska Institutet, which is directed by Dr. Macchiarini.

However, last week’s “no misconduct” ruling was based on more than 1,000 pages of documents submitted by Dr. Macchiarini and his co-authors in response to Dr. Gerdin’s report, in additional to the documents Dr. Gerdin had initially reviewed. In making this latest decision, Vice-Chancellor Anders Hamsten said that while the work in question “does not meet the university’s high quality standards,” it did not constitute misconduct.

“Now that we have examined the allegations of scientific misconduct in all seven indicted articles, we have found that they contain certain flaws but nothing that can be considered scientific misconduct,” the vice-chancellor said.

Proving that someone wilfully deceived the scientific community can be difficult to do. However, this investigation certainly demonstrated that Macchiarini’s work is fraught with problems. Certainly making an artificial trachea is a remarkable advance, but it seems as though Dr. Macchiarini’s synthetic tracheas do not work nearly as well as he claimed they do. This means that further research is required in order to properly make tracheas from a patient’s own stem cells or biomaterials or a combination thereof to treat patients with tracheal defects.