StemCells, Inc., Sued by Former Employee Who Says Their Stem Cell Treatment is Unsafe


A California stem cell company, StemCells, Inc., that is developing cell-based therapies for several different neurological and eye conditions, is being sued by a former employee (whistleblower) who claims that the company did not follow proper protocols in the preparation of their treatments. Rob Williams, who was once a senior manager at StemCells, Inc., has alleged that the company fired him after he brought these problems to the attention of senior management.

According to the Courthouse New Service, Williams in the lawsuit stated that he “noted poor sterile technique, failure to adhere to current Good Manufacturing Practices in the company’s manufacturing process, and substantial deficiencies in the company’s Manual Aseptic Processing of HuCNS-SC (Human Central Nervous System Stem Cells) cell lines—failure and deficiencies that put patients at risk of infection or death during ongoing clinical trials.”

Ken Stratton, who serves as the general counsel for StemCells, Inc., has told the California Stem Cell Report that Williams’s employment “was terminated for performance deficiencies, and [the company] finds no merit to the allegations.” Stratton also said that “the elements of manufacturing practices that concerned Mr. Williams were immediately and carefully reviewed by the company.”

It might be worth noting that this lawsuit coincides with the departure this past April or May of StemCells, Inc.’s Executive VP of Manufacturing Operations and Regulatory Affairs, Stewart Craig, who took a position at Sangamo Biosciences.

Unfortunately for StemCells, Inc., this particular lawsuit comes soon after a second bit of bad press. Embryologist Alan Trounson led the California Institute for Regenerative Medicine (CIRM) until June of this year, but has joined the board of StemCells, Inc., shortly after leaving the state stem cell research funding agency. According to an opinion article written by Ron Leuty, who is a reporter for the San Francisco Business Times, Trounson has recused himself from discussions regarding a loan StemCells, Inc., received from CIRM in 2012 because of his close relationship with the company’s founder. “But the speed of his appointment to the StemCells board has raised questions” about a possible conflict of interest, Leuty wrote.

CIRM has been marred by conflicts of interest accusations since California voters in 2004 birthed CIRM through Proposition 71 and the subsequent sale of $3 billion in state bonds. Now it has one more strike against it.

Leuty called the situation an embarrassment for CIRM. “If the public perceives that individuals—researchers or CIRM employees or company executives—are feeding at the trough of the semiautonomous public agency, it isn’t going to help CIRM get more cash from that very same public that foots the bill.”

Patient-Specific Stem Cells Made More Easily?


A Michigan State University research team uncovered the function of an already characterized gene that could be linchpin in the derivation of patient-specific stem cells that might be able to save millions of lives by differentiating into practically any cell in the body.

The gene is known as ASF1A, and even though it was not discovered by the team, ASF1A is one of the genes responsible for the mechanism of cellular reprogramming. Cellular reprogramming de-differentiates adult cells into less mature stem cells that have the capacity to differentiate into any cell type in the adult body.

This work was published in the journal Science. In this paper, the MSU team analyzed more than 5,000 genes from a human egg (oocyte) and determines that ASF1A in combination with another gene known as OCT4 and another molecule were primarily responsible for reprogramming.

Human oocytes
Human oocytes

“This has the potential to be a major breakthrough in the way we look at how stem cells are developed,” said Elena Gonzalez-Munoz, a former MSU post-doctoral researcher and first author of the paper. “Researchers are just now figuring out how adult somatic cells such as skin cells can be turned into embryonic stem cells. Hopefully this will be the way to understand more about how that mechanism works.”

An MSU team identified the thousands of genes expressed in oocytes in 2006. From this list of genes, the genes responsible for cellular reprogramming were then identified.

In 2007, a Japanese research team led by Shinya Yamanaka found that by introducing four other genes into adult cells, they could derive embryonic-like stem cells without the use of a human egg. These cells are called induced pluripotent stem cells, or iPSCs. “This is important because the iPSCs are derived directly from adult tissue and can be a perfect genetic match for a patient,” said Jose Cibelli, an MSU professor of animal science and a member of the team.

Apparently, ASF1A and OCT4 work in together in combination with a hormone-like substance that also is produced in the oocyte called GDF9 to facilitate the reprogramming process. “We believe that ASF1A and GDF9 are two players among many others that remain to be discovered which are part of the cellular-reprogramming process,” Cibelli said.

“We hope that in the near future, with what we have learned here, we will be able to test new hypotheses that will reveal more secrets the oocyte is hiding from us,” he said. “In turn, we will be able to develop new and safer cell-therapy strategies.”

Potential Marker Found for Stem Cell Population in the Inner Ear


Hearing loss is common as we get older. Presbycusis or age-related hearing loss results from the progressive death of sensory cells in the cochlea. Wouldn’t it be great if a stem cell population in the inner ear replaced these dying auditory sensory cells?

As it turns out, a stem cell population might exist in the mammalian inner ear and researchers from the UC Davis Comprehensive Cancer Center have identified a polysialylated glycoprotein that regulates neurodevelopment and is on the surface of cells in the adult inner ear. This glycoprotein acts as a marker of early cells in the inner ear and allows researchers to identify immature cells in the inner ear. This discovery was published in the journal Biochemical and Biophysical Research Communications and potentially opens the door to developing stem cell replacement treatments in the inner ear to treat certain hearing disorders.

“Hearing loss is a complex process and is usually regarded as irreversible,” said Frederic A. Troy II, principal investigator of the study from the UC Davis Comprehensive Cancer Center. “Finding this molecule in the inner ear that is known to be associated with early development may change that view.”

The existence of a marker for immature stem cells could make it possible to isolate neural stem cells from the adult inner ear in those people who suffer from hearing loss, culture and expand these cells in the laboratory, and then re-introduce them back into the inner ear as functioning neurons. These implanted cells might recolonize and establish themselves and improve hearing.

During development, certain glycoproteins (carbohydrate-protein linked molecules) are expressed on cell surfaces and serve critical functions essential to the normal growth and organization of the nervous system. One member of the class of cell-surface glycoproteins is an unusual molecule called polysialic acid or polySia. The large size of polySia allows it to fill spaces between cells and its strong electric charge repels other molecules. Therefore, polySia prevents cells from adhering or attaching to one another and thereby promotes cell movement to other areas.

Polysialic_acid_cell_interactions

Neural cell adhesion molecules (NCAMs) are also expressed on neuronal cell surfaces. As their name suggests, NCAMs help cells stick together and stay put. However, when NCAMs become modified with polysialic acid (or becomes “polysialylated”), the cells no longer adhere to other cells and are induced to migrate to new areas. Re-expression of the “anti-adhesive” polySia glycan on the surface of many adult human cancer cells facilitates their detachment, which enhances their metastatic spread.

Neural stem cells with these polySia-NCAMs on their cell surfaces play very important roles during embryonic development because these cells are able to travel throughout the body and differentiate into specialized cells. During adulthood, neural stem cells with polySia-NCAMs may migrate to injured areas and promote healing.

“The landscape of the cell surface of developing cells is decorated with a bewildering array of informational-rich sugar-protein molecules of which polysialylated NCAMs are of chief importance,” explained Troy. “During the life of a cell, these surface molecules are critical to cellular proliferation, self-renewal, differentiation and survival—essential processes for normal embryonic development and tissue regeneration in adults.”

It was already well-known that polySia-NCAM-expressing cells exist in the central nervous system, but Troy’s study is the first to document that they are also in the peripheral nervous system, and specifically in the spiral ganglia, those cluster of nerve cells in the inner ear that are essential to hearing.

Working with adult cells isolated from the inner ear spiral ganglia of guinea pigs, Troy and his team showed that these spiral ganglia cells expressed both polySia and NCAM. The polySia component was abundantly present on neural stem cells but was markedly reduced on mature cells. This implies that the polySia-NCAM complex is present on immature cells and can serve as a biomarker to identify these immature cells.

“Finding polySia-NCAM—a functional biomarker that modulates neuronal differentiation—on adult inner ear neural stem cells after differentiation gives researchers a ‘handle’ to identify and isolate these cells from among the many cells taken from a patient,” said Jan Nolta, director of the UC Davis Stem Cell Program and the university’s Institute for Regenerative Cures. “This discovery will enhance research into spiral ganglion neurons and may bring treatments closer to patients with hearing deficits.”

Lead author Park Kyoung Ho, a professor at Catholic University College of Medicine in Seoul, Korea, initiated the research for this article while on sabbatical leave in Troy’s laboratory at UC Davis. With his colleague and co-author, Yeo Sang Won, he is now planning clinical trials, based on the findings, in Korea with individuals who suffer from hearing disorders.