Category Archives: Michigan Stem Cells

Pancreatic cancer is one of the deadliest types of cancer. It is the fourth most common cause of cancer deaths in the United States. More than 43,000 people are diagnosed with pancreatic cancer each year and about the same number die each year from the disease. Only about 3% of people with pancreatic cancer live more than five years after diagnosis.

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There are several reasons why this type of cancer is so lethal

Scientists at the U-M Comprehensive Cancer Center are studying pancreatic cancer in an effort to find new and more effective treatments for patients with this deadly disease. In 2007, Cancer Center scientists were the first to identify a small group of cells, called cancer stem cells, in tumors from patients with pancreatic cancer. Researchers believe these stem cells are the key to finding an effective treatment and possibly someday a cure for pancreatic cancer.

U-M research shows that just a few cancer stem cells are responsible for the growth and spread of pancreatic cancer. Unless these stem cells are destroyed, the cancer will return. The goal of U-M scientists is to develop a new therapy targeted directly at cancer stem cells. If successful, it will be a major step forward in the treatment of pancreatic cancer.

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Since pancreatic cancer is resistant to chemotherapy and radiation, new treatments are needed that can kill the small number of cancer stem cells within the tumor. Studying pancreatic cancer stem cells will help researchers identify targets for new drugs or therapies, which can then be tested in animals and eventually in human clinical trials.

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Pancreatic Cancer Stem Cell Research | University of ...

A Michigan startup is using 3D printing technology to help surgeonsreconstruct skeletal defects helpingsurgeons minimize the need for bonegrafts to fill areas with significant missing bone.

Tissue Regeneration Systemsis developing porous, bioresorbable scaffolding that can replace itself with natural bone, leaving no residual implanted device. Instead of requiring metal plates and screws, the material is computer modeled based on CT scan input so that the implants fit a patients exact needs,CEO Jim Fitzsimmons said.

The companyjust raised $2 millionfrom existing investors, which include Venture Investors, the University of Michigan, the Michigan Economic Development Corporation and Wisconsin Alumni Research Foundation.

Rather than repairing simple fractures, the startups platform is most useful in cases of trauma, cancer where bone tumors are removed cases that require complex skeletal reconstruction.

For these kinds of clinical cases, surgeonshave to remove bone from somewhere else in the body the fibula, the scapula or part of the hip and use that to do the reconstruction, Fitzsimmons said. Our technology lets them do thatwithout the need to remove the bone from somewhere else.

The startups skeletal reconstruction and bone regeneration platform has been licensed from the Universities of Michigan and Wisconsin. It last yearreceived 510(k) approval from the Food and Drug Administration for its product that can repair neurosurgical burr holes.

The companys got a coating technology that helps it integrate the implants with an osteoconductive mineral coating that it says enhances bone regeneration and proliferation into and throughout the porous implant. Orthobiologics and bone-growing stem cells can bind easily to the coating, the company said, which allows for a controlled and sustained biologic release to accelerate new bone formation.

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Startup uses 3D printing tech to create alternative to bone grafts

Sep 04, 2014 Stem cells. Credit: Nissim Benvenisty - Wikipedia

Induced pluripotent stem cells (iPSCs)adult cells reprogrammed back to an embryonic stem cell-like statemay hold the potential to cure damaged nerves, regrow limbs and organs, and perfectly model a patient's particular disease. Yet through the reprogramming process, these cells can acquire serious genetic and epigenetic abnormalities that lower the cells' quality and limit their therapeutic usefulness.

When the generation of iPSCs was first reported in 2006, efficiency was paramount because only a fraction of a percentage of reprogrammed cells successfully became cell lines. Accordingly, the stem cell field focused on reprogramming efficiency to boost the pool of cells that could be studied. However, as scientists gained an increased understanding of the reprogramming process, they realized that myriad variables, including the ratio of reprogramming factors and the reprogramming environment, can also greatly affect cell quality.

Now researchers working in the lab of Whitehead Institute Founding Member Rudolf Jaenisch together with scientists from the Hebrew University have determined that the reprogramming factors themselves impact the reprogramming efficiency and the quality of the resulting cells. Their work is described in the current issue of the journal Cell Stem Cell.

"Postdoctoral researcher Yosef Buganim and Research Scientist Styliani Markoulaki show that a different combination of reprogramming factors may be less efficient than the original, but can produce much higher quality iPSCs," says Jaenisch, who is also a professor of biology at MIT. "And quality is a really important issue. At this point, it doesn't matter if we get one colony out of 10,000 or one out of 100,000 cells, as long as it is of high quality."

To make iPSCs, scientists expose adult cells to a cocktail of genes that are active in embryonic stem cells. iPSCs can then be pushed to differentiate into almost any other cell type, such as nerve, liver, or muscle cells. Although the original combination of Oct4, Sox2, Klf4, and Myc (OSKM) efficiently reprograms cells, a relatively high percentage of the resulting cells have serious genomic aberrations, including aneuploidy, and trisomy 8, which make them unsuitable for use in clinical research.

Using bioinformatic analysis of a network of 48 genes key to the reprogramming process, Buganim and Markoulaki designed a new combination of genes, Sall4, Nanog, Esrrb, and Lin28 (SNEL). Roughly 80% of SNEL colonies made from mouse cells were of high quality and passed the most stringent pluripotency test currently available, the tetraploid complementation assay. By comparison, only 20-30% of high quality OSKM passed the same test. Buganim hypothesizes that SNEL reprograms cells better because, unlike OSKM, the cocktail does not rely on a potent oncogene like Myc, which may be causing some of the genetic problems. More importantly, the cocktail does not rely on the potent key master regulators Oct4 and Sox2 that might abnormally activate some regions in the adult cell genome.

To better understand why some reprogrammed cells are of high quality while others fall short, Buganim and Markoulaki analyzed SNEL colonies down to the genetic and epigenetic level. On their DNA, SNEL cells have deposits of the histone protein H2AX in locations very similar to those in ESCs, and the position of H2AX seems to predict the quality of the cell. The researchers believe this characteristic could be used to quickly screen for high quality colonies.

But for all of its promise, the current version of SNEL seems unable to reprogram human cells, which are generally more difficult to manipulate than mouse cells.

"We know that SNEL is not the ideal combination of factors," says Buganim, who is currently a Principal Investigator at Hebrew University in Jerusalem. "This work is only a proof of principle that says we must find this ideal combination. SNEL is an example that shows if you use bioinformatics tools you can get better quality. Now we should be able to find the optimal combination and try it in human cells to see if it works."

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A lot of work has been done in the state of Michigan on stem cells. The University of Michigan and prestigious hospitals such as the Henry Ford Hospital and many others have been working on human stromal cells and stem cells, finding out ways in which they can be used as potential life-saving cures and treatments. Much work has been carried out to improve the outcome after stroke, traumatic brain injury, and cancer.

The laws in the state of Michigan with regard to stem cell research are different from those in other states. Michigan law bans any research that destroys embryos for nontherapeutic purposes. Michigan law also bans the use of the somatic cell nuclear transfer procedure. Many of the states that have enacted legislation prohibiting human cloning have distinguished between reproductive and therapeutic cloning, but Michigan does not. Michigan, like South Dakota, forbids therapeutic cloning.

Michigan Citizens for Stem Cell Research and Cures is a nonprofit organization formed to educate the citizens of the state of Michigan, including public officials and policy makers, about the complex science, the biomedical potential, and the current policies affecting stem cell research in Michigan to promote informed decision making on this important issue.

In 2000 the researchers at the Henry Ford Health Sciences Center Department of Neurology tested a hypothesis and found that intracerebral grafting of a combination of bone marrow (BM) with brain-derived neurotrophic factor enhances differentiation of BM cells and significantly improves motor recovery. Because most of the active studies involve rats, before involving human beings, fresh BM was harvested from adult rats. It was anticipated that this may provide a powerful autoplastic therapy for human neurological injury and degenerative disorders.

In 2001 a significant step was taken by the Department of Neurosurgery at the Henry Ford Health Sciences Center. Rats were subjected to traumatic brain injury (TBI), and marrow stro-mal cells (MSCs) were injected into the tail vein 24 hours after TBI.

The rats were killed 15 days later. It was found that MSCs injected intravenously significantly reduced motor and neurological deficits. On the basis of this data, the researchers suggested that the intravenous administration of marrow stromal cells may be a promising therapeutic strategy that may be useful in treating TBI and that warrants further investigation.

The same year, researchers tested the hypothesis that intravenous infusion of bone marrow-derived MSCs enter the brain and reduce neurological functional deficits after stroke in rats. Significant recovery of somatosensory behavior was found. To test the efficacy of various delivery routes of stem cells, the researchers injected MSCs into the internal carotid artery of the adult rat after TBI. They came up with the suggestion that intra-arterial transplantation of MSCs along with intravenous and intracerebral transplantation is also a viable route for the administration of MSCs for the treatment of TBI, as MSCs infused intra-arterially after TBI survive and migrate into the brain.

As human umbilical cord blood cells (HUCBC) are rich in stem and progenitor cells, a team of researchers went ahead and tested whether intravenously infused HUCBC could enter the brain, survive, differentiate, and improve neurological functional recovery after stroke in rats. In addition, it was also tested whether ischemic brain tissue extract selectively induces chemotaxis of

HUCBC in vitro. Treatment with HUCBC significantly improved functional recovery, and significant HUCBC migration activity also was present. Therefore, HUCBC transplantation may provide a cell source to treat stroke.

The specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Various growth factors have been shown to mediate the repair and replacement of damaged tissue. Vascular endothelial growth factor (VEGF) is a growth factor responsible for growth of new vessels. It was confirmed that intravenous infusion of human bone marrow stromal cells promotes VEGF secretion, VEGF receptor 2 expression, and angiogenesis in the ischemic boundary zone of the host brain after stroke.

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Michigan (Stem Cell) - what-when-how

The University of Michigan has recently emerged as a national leader in the three main types of stem cell research: embryonic, adult, and reprogrammed cells known as iPS cells.

A long-time leader in the study of adult stem cells, U-M has bolstered its human embryonic stem cell program, and added a complementary iPS cell research effort, since the passage of Proposal 2 in November 2008. The state constitutional amendment eased onerous restrictions on the types of embryonic stem cell research allowed in Michigan.

Recent milestones include:

In addition to the work underway by the Consortium for Stem Cell Therapies, hubs for U-M stem cell research also exist at the Life Science Institutes Center for Stem Cell Biology and at the U-M Health Systems Comprehensive Cancer Center. Other groundbreaking stem cell work is being pursued at other units across campus.

The Center for Stem Cell Biology was established in 2005 with $10.5 million provided by the U-M Medical School, the Life Sciences Institute, and the Molecular and Behavioral Neurosciences Institute.

The centers main goal is to determine the fundamental mechanisms that regulate stem cell function. That knowledge, in turn, provides new insights into the origins of disease and suggests new approaches to disease treatment. Most of the work involves adult stem cells including blood-forming and nervous system stem cells but human embryonic stem cells also are studied.

The U-M Comprehensive Cancer Center is one of the few places in North America that has made an institutional commitment to cancer stem cell research. Cancer stem cells are responsible for triggering the uncontrolled cell growth that leads to malignant tumors.

U-M researchers were the first to identify stem cells in solid tumors, finding them in breast cancer in 2003. They were also the first to find pancreatic and head-and-neck stem cells. At the U-M cancer center, scientists are investigating how these cells mutate, causing unregulated growth that ultimately leads to cancer.

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University of Michigan Stem Cell Research | Overview

Every organ and tissue in the body contains a small number of what scientists call adult stem cells or progenitor cells. These cells have three characteristics in common:

1). Adult stem cells can renew themselves through cell division for long periods of time.

2). Adult stem cells retain the ability to give rise to several (but not all) types of cells in the body.

3). Different types of adult stem cells give rise to different specialized cells. Pancreatic stem cells, for example, are the ancestors of insulin-producing islet cells in the pancreas. Hematopoietic stem cells develop into all the different types of cells in the human blood and immune systems.

Cancer stem cells are a type of adult or progenitor cell found in most types of cancer. These cells generally represent just 1% to 3% of all cells in a tumor, but they are the only cells with the ability to regenerate malignant cells and fuel the growth of the cancer.

No. Embryonic stem cells are primitive cells that form inside an early embryo. These cells also can be generated in a laboratory dish during a process called in-vitro fertilization. Four to five days after a human egg is fertilized by sperm, the dividing mass of cells is called a blastocyst. Scientists can remove the inner cell mass from the blastocyst and grow stem cells in a culture dish in the laboratory. Under the right conditions, these stem cells will retain the ability to divide and make copies of themselves indefinitely. Unlike adult stem cells, embryonic stem cells have the ability to give rise to any of the more than 200 different types of cells in the human body.

Cancer research focuses on stem cells present in malignant tumors. Researchers believe current cancer treatments sometimes fail because they don't destroy the cancer stem cells. Think of cancer as a weed: the stem cells are the root while the remaining majority of the cells are the part of the weed above ground. If you remove only the leaves but not the root, the weed will grow back. The same is true for cancer: if you do not kill the cancer stem cells, the cancer is likely to return.

In some cancer types, we are doing a good job. Most cancers when caught early can be successfully treated. But doctors still struggle to treat advanced cancers and some cancer types, such as pancreatic cancer, still have incredibly dismal survival rates. Other cancers, such as head and neck cancers, are often resistant to current therapies, making less-invasive treatments more difficult. In addition, current chemotherapies cause severe side effects because they target all rapidly dividing cells. Treatments that target only cancer stem cells would cause fewer side effects for patients.

Cancer stem cells were first identified in leukemia. U-M researchers discovered the first cancer stem cells in solid tumors, finding them in breast cancer. Since then, cancer stem cells have been identified in brain, colon, head and neck, pancreas and central nervous system tumors. Work is ongoing to identify stem cells in other tumor types.

Researchers take samples of tumors removed from patients during surgery, always with the patient's informed consent. The cells within the tumor are then sorted based on their expression of certain cell markers on their surface. Sorted cells can be injected into mice, which are then watched for new tumor growth. When only specific sorted cells form new tumors, researchers then test those cells for properties of stem cells.

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