Category Archives: Massachusetts Stem Cells

PARIS Embryonic stem cells transplanted into 18 patients with deteriorating eyesight restored some vision in more than half of the volunteers, researchers in the longest study into the fledgling technology reported Tuesday.

Stem cells derived from embryos could provide a potentially safe new source of cells for the treatment of various unmet medical disorders requiring tissue repair or replacement, its authors said.

The study marks a new chapter in the long story of embryonic stem cells, which after their discovery in the 1990s were hailed as a miracle cure but then ran into problems.

Published in The Lancet, the paper looked at a U.S. trial of stem cells among 18 patients suffering from two degenerative diseases of the retina.

Nine had a condition called Stargardts macular dystrophy, a leading cause of juvenile blindness, and nine had dry atrophic age-related macular degeneration, which occurs among the middle-aged and elderly.

There is no conventional treatment for either condition, which eventually leads to complete blindness as the retinas light-receiving cells die out.

The participants were injected with one of three doses of retinal cells derived from early-stage embryos 50,000, 100,000 or 150,000 cells.

The transplants were placed in a space under the retina of the worst-affected eye.

The patients were monitored for up to 37 months, for an average of 22 months.

Out of the 18 treated eyes, 10 showed substantial improvements in vision, as measured by the ability to read letters on a board. Of these, eight patients were able to read 15 additional letters in the first year after transplant.

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SOURCE: Siamab Therapeutics

Receives SBIR Grant Focused on Cancer Stem Cells; Research to Be Conducted in Collaboration With Massachusetts General Hospital

NEWTON, MA--(Marketwired - Oct 8, 2014) - Siamab Therapeutics, Inc., a biotechnology company developing cancer immunotherapies, today announced that Robert Mashal, President & CEO of NKT Therapeutics, has been appointed to the company's Board of Directors. In addition, the company has received a Small Business Innovation Research (SBIR) grant from the National Cancer Institute (NCI) for the development of novel therapeutic agents that target cancer stem cells (CSCs). The research will be conducted in collaboration with Bo Rueda, Ph.D, Director, Vincent Center for Reproductive Biology, Massachusetts General Hospital.

"We look forward to working with Dr. Rueda and his research team, and are honored that the NCI has awarded us this SBIR grant to develop therapies targeting cancer stem cells," said Jeff Behrens, Siamab's CEO. "We are thrilled to have Robert join our Board. His diverse background and extensive experience with emerging companies will be of great value as we continue to grow the company."

Dr. Mashal is President & CEO of NKT Therapeutics.Before joining NKT Therapeutics, Dr. Mashal was President of Alinea Pharmaceuticals.Prior to that, he was a partner at Boston Millenia Partners, a venture capital firm where he focused on investment opportunities in life sciences. He served as a Director of EpiGenesis Pharmaceuticals, Novalar Pharmaceuticals, GlycoFi, Sapphire Therapeutics, CoApt Systems, Protein Forest, and Cardiomems.He was previously a Program Executive with Vertex Pharmaceuticals, where he led cancer drug development strategy and oversaw pre-clinical/clinical development, marketing, regulatory and business activities. He was also a member of the Joint Research Committee for the $800 million Vertex-Novartis collaboration. Prior to that, Dr. Mashal served as a consultant at McKinsey & Company, and a faculty member and Attending Physician at Dana-Farber Cancer Institute, Brigham & Women's Hospital, and Harvard Medical School. Dr. Mashal is a diplomate in both internal medicine and oncology and a graduate of Johns Hopkins University. Dr. Mashal received his M.D. from Johns Hopkins University School of Medicine.

"I am excited to be joining Siamab at such a critical stage in the company's growth and look forward to providing support and guidance to the management team," said Robert Mashal. "Siamab has an impressive technology platform with tremendous potential for developing innovative cancer immunotherapies."

Under the SBIR grant recently awarded, Siamab will collaborate with Dr. Rueda's lab to explore the potential of Siamab's technology to create anti-glycan antibodies that target specific populations of cancer stem cells and explore the relationship between tumor associated carbohydrate antigens ("TACAs") and CSCs.

"Targeting CSCs represents a promising approach to the treatment of cancer," said Dr. Rueda. "I look forward to working with Siamab to explore the potential of their agents to target and inhibit the growth of CSCs."

Cancer stem cells (CSCs) are a subset of tumor cells that possess characteristics associated with normal stem cells. Specifically, they have the ability to self-renew, differentiate and generate the diverse cells that comprise the tumor. CSCs have been identified and isolated in several human cancer types, including breast, brain, colon, head and neck, leukemia, liver, ovarian, pancreas and prostate. These CSCs represent a small percentage of the tumor as a distinct population and cause relapse and metastasis by giving rise to new tumors. While chemotherapy and other conventional cancer therapies may be more effective at killing bulk tumor cells, CSCs are thought to escape and seed new tumor growth due to their quiescent and chemoresistant properties. Therefore, traditional therapies often cannot completely eradicate tumors or prevent cancer recurrence and progression to metastasis. With growing evidence supporting the role of CSCs in tumorigenesis, tumor heterogeneity, resistance to chemotherapeutic and radiation therapies, and the metastatic phenotype, the development of specific therapies that target CSCs holds promise for improving survival and quality of life for cancer patients, especially those with metastatic disease.

About Siamab Therapeutics, Inc. Siamab Therapeutics, Inc. is a biopharmaceutical company developing novel cancer immunotherapies.Siamab has developed a platform of technologies that enable the rapid discovery and development of therapeutic antibodies that bind to a novel class of carbohydrate antigens present on cancer cells, tumor associated carbohydrate antigens (TACAs). Siamab has developed a patented set of technologies to identify and precisely assay anti-TACA antibodies -- enabling rapid discovery and screening of candidate antibodies as well as characterization of binding epitopes.The company's lead program is in preclinical studies for the treatment of solid tumors. Siamab's corporate headquarters are in Newton, MA and laboratory facilities are in San Diego, CA. Learn more at http://www.siamab.com

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Siamab Therapeutics Appoints Robert Mashal to Board of Directors

Research Projects

Characterizing glioblastoma stem cells

One of the main research focuses of the Brain Tumor Stem Cell Lab (Wakimoto Lab) is to characterize glioblastoma stem cells isolated from patient tumors. We are extensively establishing glioblastoma stem cells that grow in culture and testing their ability to form experimental brain tumors in mice. Our research shows that the capability of glioblastoma stem cells to migrate and invade through the brain varies greatly between patients. We are interested in identifying the molecular mechanisms that control tumor invasiveness. These studies are being conducted in close collaboration with the laboratories of Drs. Martuza, Rabkin, Curry, Cahill, Batchelor and Chi at Massachusetts General Hospital.

Therapeutic development

Glioblastoma stem cells are considered resistant to therapy such as chemotherapeutic drugs, but our research suggests that this is not always the case. Using glioblastoma stem cells as a unique model system that preserves patient-specific disease characteristics, we are evaluating the efficacy of therapeutic agents that include oncolytic herpes simplex virus -1 (in collaboration with the Martuza and Rabkin laboratories) and novel molecular targeting agents (in collaboration with the Batchelor and Chi Laboratories), and trying to discover molecular signatures of cells that help predict effectiveness for such treatment. Working closely with the Shah Laboratory of Radiology at Mass General, we are conducting research that harnesses normal stem cells to deliver therapeutic viruses to glioblastoma in the brain.

Glioblastoma recurrence

Cancer recurrence after surgery, radiation and chemotherapy is a serious issue that makes the management of glioblastoma difficult. We are trying to understand the role glioblastoma stem cells play in the relapse of the tumor. Our approach to this task is to establish glioblastoma stem cells from tumors both before and after therapy, and compare the two stem cells through analysis of their molecular and biological characteristics.

Collaboration

Taking advantage of the rich scientific environment at Mass General, the Brain Tumor Stem Cell Lab (Wakimoto Lab) works closely with the laboratories of Drs. Martuza, Rabkin, Curry, Cahill, Batchelor, Chi, Bernstein, Mohapatra, Iafrate and Shah. We are part of the Molecular Neurosurgery Lab and the Brain Tumor Research Center.

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Brain Tumor Stem Cell Lab - Massachusetts General Hospital ...

Published time: March 10, 2014 22:34

Reuters/Wolfgang Rattay

The US Food and Drug Administration has granted approval to Pluristem Therapeutics to mass produce therapeutic human-placenta-derived stem cell products within its commercial-scale manufacturing facility in Haifa, Israel.

Pluristems Placental Expanded (PLX) products are mesenchymal-like adherent stromal cells connective tissue cells in an organ from human placentas, which are lush with hormones and proteins. The FDA has cleared PLX for use in studies on treating injuries, one step closer to full approval of PLX cells in treatments.

PLX products are made via Pluristems automated 3D cell expansion manufacturing platform that uses its patented high-throughput culturing technologies, 3D bioreactors, and downstream equipment.

The PLX cells are grown using the companys proprietary 3D micro-environmental technology and are an off-the-shelf product that requires no tissue matching prior to administration, according to Pluristem.

Pluristem operates out of a high-output facility in northern Israel that can produce about 150,000 doses of PLX products a year.

"We believe we have the largest, scalable, most efficient, most consistent and controlled process for manufacturing cell therapies," Zami Aberman, chairman and CEO of Pluristem, said in a statement. "Knowing that the 'Process is the Product' in cell therapy, we have established our leadership position in the industry by focusing on our 3D commercial scale cell manufacturing processes.

Pluristems use of human placenta to boost cell repair involves a drug delivery platform that releases a cocktail of therapeutic proteins in response to a host of local and systemic inflammatory and ischemic diseases.

Though animal placenta, especially from horses, has been a popular form of treatment for cell repair, human placenta offers a naturally compatible genome.

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Mass production of placenta stem cells gets FDA approval ...

Embryonic Development of the Inner Cell Mass:

The fourth cleavage event of the developing embryo results in a nonpolarizedinner cell mass(ICM, pluriblast,embryoblast), enveloped by the outer, polarizedtrophoblastlayer of cells. The trophoblast cells form an inner cavity (blastocoele), whose formation indicates the bastocyst stage. While the trophoblast will ultimately form the outerchorionicsac and the fetal component of theplacenta, the inner cell mass, will give rise to all embryonic tissues and to some of the extraembryonic membranes.

The ICM segregates into abilaminar embryonic disc(bilaminar blastoderm) which consists of two epithelial layers, each of a distinct lineage: the external (dorsal)epiblastand the internal (ventral)hypoblast. The next developmental stage is gastrulation, in which waves of migrating cells convert the ICM into a trilaminar embryonic disc, which is comprised of three germ layers (ectoderm, mesoderm and endoderm) that contribute to the formation of many organs, often with contributions of two or all three of the germ layers.

The ectoderm forms the central andperipheral nervous systemsandepidermis, and contributes to theadiposeandheartas well as to numerous other organs. The ectoderm forms many of thesensory organs(eye, ear, nose), and is also the source of Rathke's pouch, an invaginating diverticulum of the stomodeal roof which ultimately detaches from the stomodeum and becomes the adenohypophysis of the pituitary gland.

The mesoderm produces and contributes to theblood,endothelium,heart,kidney,reproductive system,bones,skeletal, smooth muscleand connective tissues. The mesoderm also contributes totendons,ligaments,dermisandcartilage.

The endoderm produces thegut tubeand its derived organs, including the cecum, intestine, stomach, thymus, liver,pancreas,lungs,thyroidandprostate.

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Inner Cell Mass - Embryonic Development & Stem Cells ...

Analysis of circulating tumor cells (CTCs) in a mouse model of pancreatic cancer identified distinct patterns of gene expression in several groups of CTCs, including significant differences from the primary tumor that may contribute to the ability to generate metastases. In their study reported in the Sept. 25 issue of Cell Reports, investigators from the Massachusetts General Hospital (MGH) Cancer Center identified several different classes of pancreatic CTCs and found unexpected factors that may prove to be targets for improved treatment of the deadly tumor.

"Our ability to combine a novel microfluidic CTC isolation device, developed here at MGH, with single-cell RNA sequencing has given us new biological insights into these cells and revealed novel avenues to try and block the spread of cancer," says lead author David T. Ting, MD, MGH Cancer Center.

Pancreatic cancer is among the most deadly of tumors because it spreads rapidly via CTCs carried in the bloodstream. The earliest technologies for isolating CTCs from blood samples relied on interactions with known tumor-specific marker proteins, potentially missing cells that did not express those particular markers. The device used in the current study, called the CTC-iChip, enables the isolation of all CTCs in a blood sample, regardless of the proteins they express on their surface, by removing all other components. Since the CTCs collected are in solution, unlike with previous CTC capture devices, they are suitable for advanced RNA sequencing techniques to reveal the gene expression patterns of each individual cell.

Using a well-known mouse model of pancreatic cancer, the researchers first isolated 168 single CTCs from the bloodstreams of five individual mice. Analysis of the RNA transcripts of each CTC revealed several different subsets of CTCs, based on gene expression patterns that were different from each other and from the primary tumor. The largest subset, which the authors call 'classic CTCs,' was found to have elevated expression of a stem cell gene called Aldh1 a2, along with genes characteristic of two basic cell types -- epithelial and mesenchymal -- transition between which has been associated with tumor metastasis. Another gene expressed by almost all classic CTCs, Igfbp5, is only expressed in primary tumor at locations where epithelial cancer cells interface with the supporting stromal cells that provide a nurturing microenvironment, an observation that suggests that those regions may be the source of CTCs.

The research team was most surprised to observe that extracellular matrix (ECM) genes in general -- usually expressed primarily in stromal cells -- were highly expressed in all classic CTCs. Previous studies have suggested that the establishment of metastases depends on the appropriate cellular microenvironment -- 'soil' in which CTCs can plant themselves as 'seeds'- and that the expression of ECM genes is an important aspect of that environment. Expression of ECM genes by CTCs themselves suggests that the blood-borne cells may provide or help prepare their own 'soil.'

Analysis of CTCs from blood samples of human patients with pancreatic, breast or prostate cancer also found elevated expression of several ECM genes. One particular gene, SPARC, was highly expressed in all pancreatic CTCs as well as in 31 percent of breast CTCs. Further experiments revealed that suppressing SPARC expression in human pancreatic cancer cells reduced their ability to migrate and invade tissue, and significantly fewer metastases were generated when SPARC-suppressed pancreatic tumors were implanted into a mouse model, supporting the protein's role in a tumor's metastatic potential.

"Given our limited therapeutic options for pancreatic cancer, understanding the role of the ECM in this tumor seems to be of great importance," says Ting, who is an assistant professor of Medicine at Harvard Medical School. "Much effort has been focused on targeting the microenvironment to improve the efficacy of chemotherapy, and data indicating that environmental stromal cells can enhance a tumor's metastatic ability indicate that ECM proteins are important whether they are produced in stroma or within the tumor cells themselves. Now we need to investigate whether therapeutically targeting ECM can destroy both the tumor microenvironment and CTCs before they have a chance to metastasize."

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The above story is based on materials provided by Massachusetts General Hospital. Note: Materials may be edited for content and length.

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Gene expression patterns in pancreatic circulating tumor cells revealed

The ALS ice bucket fundraising phenomenon sweeping across social media wont be chilled by a Cincinnati church leaders objection to the organization backing embryonic stem cell research, a local theologian predicted.

I dont think that bishops really give marching orders to lay people, said Stephen Pope, a theology professor at Boston College. I dont know that the statement is really going to have much impact.

He added that the Catholic Church teaches against the use of birth control, but that most Catholics who are married, at some point, use birth control.

The Herald reported yesterday that Jim Rigg, the superintendent of Catholic schools for the Cincinnati archdiocese, told students to avoid donating to the ALS Association because it supports research using embryonic stem cells, which runs counter to church teachings.

John Frates, the Catholic Beverly father of former BC baseball player Peter Frates who inspired the ice bucket challenge, told the Herald this week he understands the objections, but he just wants a cure for his son.

Although people giving to the ALS Association can direct their donations away from embryonic stem cell studies, its still a cooperation with evil, according to John Di Camillo, staff ethicist at the National Catholic Bioethics Center.

Just as theyre raising awareness to try and eliminate ALS, we want to raise awareness of the immorality of stem cell research and have that eliminated, he said.

The ALS Association said it has raised $41.8 million nationwide since the ice bucket challenge was launched last month 14 times the amount it raised during this time last year.

The organization only gives money to one stem cell study, according to Jan Obermann, care services manager for the nonprofits Massachusetts chapter.

The U.S. Conference of Catholic Bishops has called the Cincinnati protest a local matter.

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Expert: Catholic objections wont leave ALS fundraiser all wet

Youd probably think that raising millions of dollars to fund research to find a cure for a terminal illness that robs sufferers of the ability to move or speak would be a good thing. Well, some pro-life advocates found a way to disagree.

Pro-life activists and religious leaders are encouraging people to stop donating to the ALS Association. Their logic: at least one of the studies funded bv the ALS Association uses embryonic stem cells, and embryos (i.e. babies) must be killed in order to harvest those cells. While those opposed to the research are still okay with the pouring of cold water over ones head, they want donations to instead go to ALS charities that only fund research that uses adult stem cells, or that dont fund research at all.

In an article titled The ALS challenge kills babies, the American Family Associations Kevin McCullough wrote: Millions of dollars raised through this specific challenge may be used to create a child only to kill it for what amounts to fruitless experimentation and this very challenge is contributing to the on going destruction of human life--intentionally.

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According to New York magazine, it was pro-life news site LifeNews.com that first advocated against donating to the ALS Association, saying: if you give to the ALS Association your money may end up supporting clinical trials that use aborted fetal cells. Even if the money is not directly going to facilitate such research, it will be going to organizations that see no problem in using aborted innocents as biological material for medical use.

LifeNews suggested giving money to Team Gleason instead, as it helps people with ALS but does not appear to fund any research into curing the disease. Team Gleason is named after Steve Gleason, a former NFL player who has ALS. Incidentally, Gleason took part in the ice bucket challenge last week. He told the Seattle Times that ALS is a silent, brutal, and until now an anonymous death. There is still no treatment or cure ... So, my advice is to pour ice over your head, donate, learn, share and care for someone with ALS.

The anti-ALS Association cause was recently taken up by the Archdiocese of Cincinnati, which encouraged area Catholic schools to tell students to donate money to the John Paul II Medical Research Institute. The Institute does not use embryonic stem cells. Cincinnati Catholic schools superintendent Jim Rigg did just that when he took part in the ice bucket challenge on Thursday:

In trying to explain how it could advocate taking money out of a charitys pocket, a spokesperson for the Archdiocese told another pro-life website, LifeSiteNews.com: Its a well established moral principle that a good end is not enough. The means to that end must be morally licit.

The Christian Broadcasting Network followed suit, posting a video of some of its employees dumping water on themselves and making it clear that they would not be donating to the ALS Association:

Time reports that the John Paul II Medical Research Institute has received dozens of donations since the anti-ALS Association challenge began.

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Theres a New Anti-ALS Association Ice Bucket Challenge

Massachusetts Laws

MGL c.111L Biotechnology. Law says, in part, "it shall be the policy of the Commonwealth to actively foster research and therapies in the life sciences and regenerative medicine by permitting research and clinical applications involving the derivation and use of human embryonic stem cells..."

105 CMR 960: Biotechnology. As amended, to implement the law above.

Dickey-Wicker Amendment, P.L. 104-99, sec.128. Prohibits use of Federal funds for "(1) the creation of a human embryo or embryos for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero..."

Executive Order: Removing Barriers to Responsible Scientific Research Involving Human Stem Cells, March 9, 2009. "For the past 8 years, the authority of the Department of Health and Human Services, including the National Institutes of Health (NIH), to fund and conduct human embryonic stem cell research has been limited by Presidential actions. The purpose of this order is to remove these limitations on scientific inquiry."

National Institutes of Health Guidelines for Human Stem Cell Research, 74 Fed Register 32170, July 7, 2009.

Sherley v. Sebelius, US Dist Court - DC, Civ. No. 1:09-cv-1575, August 23, 2010. Premilinary injunction granted "to enjoin defendants from implementing the [NIH] Guidelines [for Human Stem Cell Research] because the Guidelines allow federal funding of ESC [Embryonic Stem Cell] research, which involves the destruction of embryos."

Stem Cell Information, National Institutes for Health. Includes links to basic information, federal policy, research topics and information for researchers.

Stem Cell Research, The Center for Bioethics and Human Dignity. Links to articles expressing concerns about stem cell research.

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Mass. Law About Stem Cell Research - Massachusetts Trial ...