Category Archives: California Stem Cells

By Ciara Curtin

Jeanne Loring and her Scripps Research Institute colleagues transplanted a set of cells into the spinal cords of mice that had lost use of their hind limbs to multiple sclerosis. As the experimentalists expected, within a week, the mice rejected the cells. But after another week, the mice began to walk.

We thought that they wouldnt do anything, says Loring, who directs theCenter for Regenerative Medicineat Scripps. But as her lab has since shown numerous times, and published in Stem Cell Reports, something that these particular so-called neural precursor cells dobeforethe immune system kicks them out seems to make the mouse better.

The cells Lorings team used are derived from induced pluripotent stem cells, which are mature cells, such as skin cells, that have been coaxed with a combination of chemicals to return to an earlier stage of development.

Induced pluripotent cells, also known as iPS cells, pose a number of opportunities for medicine. For instance, Loring is using iPS cells from Parkinsons disease and multiple sclerosis patients to reconstitute cell types that may be damaged in people with those conditions. She is also using them to test how certain drugs or treatments may affect damaged cells in people with conditions such as autism spectrum disorders.

Loring (front row, center) with the Loring Lab Group at the Center for Regenerative Medicine

Loring says no viable long-term treatments exist for the diseases her team has been working on, including Alzheimers disease, Parkinsons disease, and multiple sclerosis, Thats where the need is, she says.

The neural precursor cells that Loring has been using in the mice with MS are young cells that havent quite gotten to the point of being nerves yet. Only certain types of these cells have such a dramatic Lazarus-like effect on the affected mice, but Lorings team can readily identify them based on DNA analysis.

Even so, theyre not yet ready to treat human MS patients with the approach, she says. First, the researchers want to identify what the cells producea protein, perhaps, or a set of proteinsthat allows the mice to walk.

For other diseases, however, researchers are closer to being ready to transplant working versions of reprogrammed cells into sick people.

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Could Reprogrammed Cells Fight 'Untreatable' Diseases?

Yeo Lab Takes the ALS Ice Bucket Challenge

Principal Investigator Gene Yeo and his lab take the ALS Ice Bucket Challenge to raise awareness about Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease. For more information, visit the ALS Ice Bucket Challenge andYeo Labwebsites.

The Sanford Stem Cell Clinical Center at UC San Diego Health System exists to transform the enormous potential of stem cell science into real therapies for patients. More information is available on the UC San Diego Health Systems website.

The La Jolla Light features an article by Dr. Scott Lippman on the Sanford Consortium's unprecedented collaboration of five leading scienfic institutions to advance stem cell research; "critical to catalyze major advances in cancer research and care."

This 2010 CBS News feature explores the danger of bogus therapies using stem cells.

The Hertzberg Schechter awards committee unanimously approved Dr. Beatriz C.G. de Freitas for the prize, valued at $10,000, to support a research trip to the Weizmann Institute in Israel to engage in collaborative research and seed collaborative research for two to four weeks. Dr. Freitas is interested in modeling normal and affected early stages of human nervous system development using pluripotent stem cells, focusing on human astrocytes. (Image: [left to right] Richard Hertzberg; Sylvia M. Evans, Ph.D; Beatriz Freitas, Ph.D; Larry Goldstein, Ph.D)

The selection committee is seeking applicants who have an MD degree, are in a fellowship program at UC San Diego, have stem cell related research projects in mind, and have time available during their current fellowship to pursue them. Stipends are competitive, and recipients can perform up to 25% clinical service. Please email jbraswell "@" ucsd.edu for more info.

Larry Goldstein speaks at an event held by the California Healthcare Institute at the Salk Institute in July, 2013, covered by the San Diego Union-Tribune.

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UC San Diego Stem Cell Program

All that talk about the agency running out of money for new awards in 2017? Bushwa, he basically said. Its simply not true, he told the directors of the agency at their meeting in Millbrae.

Mills' comments appeared to be directed at media stories, including those on this Web site, that mention the 2017 timetable. However, the date was not concocted by the writers of those stories. It came directly from the agency itself, which has never challenged it until Mills did last week. The timetable was even referenced as recently as December 2013 by the agencys directors.

A case in point came last week when Mills recommended and the board approved slicing $5 million out of a $15 million component of the agencys Alpha clinic RFAs. It was the first time that the board has so heavily cut a previously approved "concept" figure.

Pat Olson, executive director of scientific activities, said,

Enter Mills five months later as president. By last week, he was telling board members that, yes, they have enough money to give out awards until 2020 at a rate of $190 million a year. He said that about $1 billion is available.

Of course, if the agency spends more than $190 million a year, the money will run out faster. And the agency is engaged in clinical trials and commercialization efforts, which are far more expensive than basic research.

But Mills 2020 timetable has some significant advantages even if it slows the pace of awards. It gives the agency substantially more time to arrange some sort of financing for the future. Currently its only real source of funding is state bonds. Its ability to authorize those bonds ends in 2017, according to the agency. Currently Thomas is examining the possibility of some sort of private-public financing arrangement. Asking voters to approve another bond measure has not been ruled out, but it could be problematic politically. The additional time would improve the possibility that clinical trial results would emerge that would resonate with the public as well as with private funding sources.

While Mills paints a rosier financial picture than the agency previously offered, he also has demonstrated a clear fondness for focused austerity. It fits with the mood of the board. Juelsgaard, who is chairman of the agencys Finance Subcommittee, is also attempting to bring a sharper financial perspective to the agency at a time when directors are clearly feeling a pinch.

Instead last December, after directors were told that only $629 million out of $3 billion was left uncommitted, CIRM DirectorJeff Sheehy, in a comment echoed in tone by other board members, said,

One of Mills first public actions involved the agencys $17 million annual operational budget, which is limited by state law. On top of those limitations, in May he whittled the spending plan down to the point where it could be described as less than the previous fiscal year, given inflation.

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California Stem Cell Report - blogspot.com

One recent headline in Forbes magazine read, Stem Cell Therapy To Fix The Heart: A House Of Cards About ToFall? A provocative new study calls into question the rationale for using stem cells to repair the heart a much-hyped experimental therapy that grew out of insights from a groundbreaking Boston researchers laboratory. But it appears that heart stem cell regeneration is like cheese, you might say. There are many different varieties. And in the case of a $27 million investment in heart cell regeneration by the California stem cell agency, all the players say things are just fine with their project.

The state's research effort involves a publicly traded company called Capricor Therapeutics. The Beverly Hills firm and one of its founders. Eduardo Marban, director of the Cedars-Sinai Heart Institute in Los Angeles, received the $27 million from the state stem cell agency.

In the wake of the news reports involving heart stem cell regeneration, the California Stem Cell Report queried both Marban and the stem cell agency. Marban replied within 37 minutes last week. Here is the text of what he had to say in his email.

Although some alarmist headlines have inappropriately questioned all cardiac stem cell work, the issues have to do with only one specific subtype of cardiac stem cell, which is marked by the expression of an antigen called c-kit. This is NOT the cell type being developed by Capricor; in fact, my laboratory has found that c-kit-positive cells play no role in Capricors cell product. That product, known as CAP-1002, contains a small fraction (less than 5 percent) of c-kit-positive cells which can be completely removed with no loss in potency. CAP-1002 is believed to work by indirect 'paracrine' mechanisms that differ fundamentally from those postulated for the c-kit-positive cells.

These concerns in no way undermine Capricors technology. In fact, CAP-1002 remains the only heart-derived cell product in commercial development. I am proceeding full speed ahead with mechanistic and translational work on CAP-1002, and Capricor continues to feel bullish about the product, which is now in phase 2 trials (the furthest along of any CIRM-funded project).

Kevin McCormack, a spokesman for the stem cell agency, also said that Capricor is using a different method and a different stem cell than the one being called into question.

(Editor's note: If you would like a copy of the Nature paper that Marban referenced, please send an email to djensen@californiastemcellreport.com.)

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California Stem Cell Report: Capricor and California Stem ...

Overview of Cancer Immunotherapy

The immune system deals with cells and organisms that express foreign antigens by a process of antigen presentation to T cells then communication with B cells. This is followed by the production of cytotoxic T cells that can recognize antigens, and the production by differentiated B cells of antibodies that target those antigens. The system also has a memory process so that if an antigen is seen again, the immune response is mobilized even faster. T cells are capable of killing tumor cells. However, there are feedback mechanisms in many diseases, particularly cancer, that can turn off and/or repress the processes of antigen recognition and immune response.

Some experts have suggested that within 10 years, 60% of cancers will be treated with immunotherapy (Nature, Vol. 508, 3 April 2014). Immune responses can be induced and/or enhanced by vaccination using a single or handful of well-characterized tumor antigens. Injections of exogenously expanded cytotoxic T cells that recognize a single antigen on a patients cancer have been shown to eliminate metastatic disease in a subset of patients. However, cancers do not express a single antigen. Further, it is now known that most of these mutations are unique to that patients cancer; so it is not surprising that approaches that have involved immunization with only one or a few antigens, or injections of someone elses cultured tumor cells have not been successful.

We believe that a better approach would involve a broader array of antigens and would utilize the patients own tumor, also known as autologous tumor. A number of those methods that have been tried have sought to draw antigens from an entire tumor mass. However, the cells of interest are the cancer stem cells or replicating cells, those with indefinite multiplicative capability. Only a few of those cells are present in the tumor mass, perhaps as few as 1/100,000 cells have this potential. Moreover, the tumor mass by definition includes a variety of other cells, such as immune cells, blood cells and other cells, some or many of which may inhibit or otherwise interfere with antigen recognition.

NeoStems approach is different in two fundamental ways from other autologous therapies: (i) it presents to the patients immune system the entire spectrum of antigens from that patients own tumor and (ii) it separates out and re-administers just those cells from the patients tumor that are self-renewing, that is, those that can regenerate the cancer and cause metastatic spread against which an immune response is most needed. Those cells are pretreated with radiation and are connected to a dendritic cell to optimize presentation to the T cell.

Basic and clinical research have established that in some patients there is the ability to recognize tumor antigens, but as a result of their disease there are mechanisms that interfere with this process, while other patients have an existing immune recognition of tumor antigens, but their immune response is being suppressed. This is the basis for the new monoclonal antibody therapies such as anti-CTLA4, anti-PD-1, and anti-PD-L1 that are providing clinical benefit in the setting of metastatic melanoma. These so-called checkpoint inhibitors, i.e., drugs that block checkpoint proteins, work by either stimulating an existing immune response to tumor antigens, or liberating a repressed immune response to tumor antigens. However, their mechanisms of action rely on pre-existing recognition of tumor antigens by the immune system. NeoStems approach is different in that it is designed to induce or enhance recognition of all the tumor antigens expressed on the tumors self-renewing cells. In other words, the therapys intent is to increase the target specifically, its self-renewing stem cells.

The lead candidate in the program is the Companys DC/TC (dendritic cell/tumor cell) product*, a treatment for malignant melanoma. In a Phase 2 randomized clinical trial of subcutaneously injected DC/TC,DC/TC improved two year overall survival in patients with advanced melanoma (recurrent Stage III or Stage IV) to 72% compared to 31% for control patients treated with only their own tumor cells suspended in granulocyte macrophage colony stimulating factor (GM-CSF) (p=0.007). The toxicity profile was favorable with no grade IV and only one grade III (allergic reaction) event in the study. The allergic reaction was attributed to the granulocyte macrophage colony-stimulating factor (GMCSF), an FDA-approved immune stimulant used in the final drug formulation. There were no other significant toxicities seen in either an earlier single-arm Phase 2 trial or this randomized Phase 2 trial. Local injection site reactions, such as skin irritation and itching, did occur, but the symptoms dissipated within hours after the injection. There were no significant adverse effects on hematopoietic cells or renal function, liver function, or patient performance status. View Phase 2 trial results.

NeoStems immunotherapeutic approach is a platform technology that NeoStem believes could be expanded into other indications, such as hepatocellular carcinoma and other immune responsive tumor types.

* NeoStem has submitted a United States Adopted Names Council application for the Companys DC/TC product for metastatic melanoma to use the generic name Melapuldencel-T.

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Targeted Cancer Immunotherapy - NeoStem | Cell Therapy ...

En Espaol

With funding from CIRM available to California researchers, the state is in a unique position within the United States. Learn more about how CIRM changes the landscape of research in California and about laws in other states.

As the largest source of funding for stem cell research outside the NIH, CIRM is funding novel research pathways in addition to identifying hurdles to new stem cell therapies and specifically funding approaches to overcome those barriers.

CIRM has funded buildings that are needed in order to do the research without the restrictions that came with federal funding under President Bush.

CIRM Major Facilities Speed Stem Cell Science and Create Jobs [4:20]

CIRM's rounds of funding have specifically targeted areas that will help push stem cell research toward the clinic. Our SEED grants pulled more scientists into stem cell research and the Comprehensive awards supported California's leading stem cell scientists. CIRM encouraged young faculty to commit their labs to stem cell science through two rounds of New Faculty awards, which support those faculty for five years. Training grants and Bridges awards ensure a next generation of stem cell scientists and laboratory personnel to fill the needs of a growing stem cell research sector in Calfiornia.

This NPR story discusses the value of stem cell funding in California:

CIRM's research grants pull new science into the stem cell pipeline with the Basic Biology awards. These awards also create a better understanding of stem cell biology, which helps scientists at all stages of developing new therapies. The Tools and Technologies awards support the creation of new technologies and tools for overcoming barriers in stem cell research. These will help ensure that the ideas coming out of basic research move quickly down the pipeline to new therapies. The Early Translational awards fund research that moves basic ideas towards therapeutic targets -- a critical step in developing new cures that is traditionally difficult to to fund.

The recent Disease Team awards create a unique collaborative approach to science. Rather than funding individual scientists working in isolation, these innovative awards require scientists to work together to overcome barriers. These teams are committed to bringing a therapy to the FDA within four years -- a dramatic reduction in the normal time required for this stage research. By being strategic about what types of research get funded CIRM will speed the time it takes to go from basic research to new therapies that help treat incurable diseases.

Stem cell research has the potential to treat diseases that currently have high health care costs. Diabetes, for example, is among the most expensive chronic diseases. People with the disease require regular injections of insulin, monitoring equipment, regular doctor visits and have higher healthcare costs due to the eye, kidney, cardiovascular, and neural effects of the disease. Even if a stem cell-based therapy doesnt entirely cure the disease, reducing its impact would be an enormous economic benefit.

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Stem Cell Research in California | California's Stem Cell ...

Stem cells have recently generated more public and professional interest than almost any other topic in biology. One reason stem cells capture the imagination of so many is the promise that understanding their unique properties may provide deep insights into the biology of cells as well as a path toward treatments for a variety of degenerative illnesses.

Stem cells create, through cell division, new cells capable of becoming various types of tissue cell; heart, pancreas, spleen or any of up to 220 different types of cells. When this division occurs, the original stem cell splits into two cells, one with the morphing ability and the other with all the characteristics of the original stem cell. As this process repeats, damaged tissue is replaced at an accelerated rate. Typically, these cells lie dormant until activated by the body in order to promote healing and repair. This natural process is slow and for many reasons can become hampered or cease to occur at all.

Our process extracts, concentrates, and most importantly, activates these stem cells which we then return to the same body, where needed, to affect the desired and most favorable results. For a more detailed explanation click here.

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Stem Cells Therapy in California