Insulin, Nutrition Prevent Blood Stem Cell Differentiation in Fruit Flies

Newswise UCLA stem cell researchers have shown that insulin and nutrition keep blood stem cells from differentiating into mature blood cells in Drosophila, the common fruit fly, a finding that has implications for studying inflammatory response and blood development in response to dietary changes in humans.

Keeping blood stem cells, or progenitor cells, from differentiating into blood cells is important as they are needed to create the blood supply for the adult fruit fly.

The study found that the blood stem cells are receiving systemic signals from insulin and nutritional factors, in this case essential amino acids, that helped them to maintain their stemness, said study senior author Utpal Banerjee, professor and chairman of the molecular, cell and developmental biology department in Life Sciences and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine at UCLA.

We expect that this study will promote further investigation of possible direct signal sensing mechanisms by mammalian blood stem cells, Banerjee said. Such studies will probably yield insights into chronic inflammation and the myeloid cell accumulation seen in patients with type II diabetes and other metabolic disorders.

The study appears March 11, 2012 in the peer-reviewed journal Nature Cell Biology.

In the flies, the insulin signaling came from the brain, which is an organ similar to the human pancreas, which produces insulin. That insulin was taken up by the blood stem cells, as were amino acids found in the fly flood, said Ji Won Shim, a postdoctoral fellow in Banerjees lab and first author of the study.

Shim studied the flies while in the larval stage of development. To see what would happen to the blood stem cells, Shim placed the larvae into a jar with no food - they usually eat yeast or cornmeal and left them for 24 hours. Afterward, she checked for the presence of blood stem cells using specific chemical markers that made them visible under a confocal microscope.

Once the flies were starved and not receiving the insulin and nutritional signaling, all the blood stem cells were gone, Shim said. All that were left were differentiated mature blood cells. This type of mechanism has not been identified in mammals or humans, and it will be intriguing to see if there are similar mechanisms at work there.

In the fruit fly, the only mature blood cells present are myeloid cells, Shim said. Diabetic patients have many activated myeloid cells that could be causing disease symptoms. It may be that abnormal activation of myeloid cells and abnormal metabolism play a major role in diabetes.

Metabolic regulation and immune response are highly integrated in order to function properly dependent on each other. Type II diabetes and obesity, both metabolic diseases, are closely associated with chronic inflammation, which is induced by abnormal activation of blood cells, Shim said. However, no systemic study on a connection between blood stem cells and metabolic alterations had been done. Our study highlights the potential linkage between myeloid-lineage blood stem cells and metabolic disruptions.

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Insulin, Nutrition Prevent Blood Stem Cell Differentiation in Fruit Flies

International Stem Cell Corporation Completes $5 Million Financing and Elects Jim Berglund to the Board of Directors

CARLSBAD, Calif.--(BUSINESS WIRE)--

International Stem Cell Corporation (OTCBB:ISCO.OB - News) http://www.internationalstemcell.com, a California-based biotechnology company focused on therapeutic, cosmetic and research products, announced today that it had obtained new capital financing and made important changes in the composition of its Board of Directors to ensure that Independent Directors hold the majority of Board seats.

The financing consists of $5 million in newly issued Series G Convertible Preferred Stock (without warrants), convertible into Common Stock at a conversion price of $0.40/share, the market price of the Companys Common Stock on the date the offer to purchase was made. This financing was made by AR Partners LLC, a healthcare investment firm owned by Dr. Andrey Semechkin, ISCOs CEO and Co-Chairman of the Board of Directors.

Concurrently with the closing of this financing, the Company elected to its Board of Directors Dr. James Berglund, co-founder of Enterprise Partners Venture Capital - one of the premier venture capital firms in the field of healthcare technology founded in 1985. Dr. Berglund, with his extensive professional experience, continues as an active participant in the biotech and healthcare industries. Dr. Berglund will replace Kenneth C. Aldrich, co-founder and former CEO of the Company during the period 2008-2009, who is stepping down as ISCO Board of Directors Co-Chairman. Although Mr. Aldrich is retiring from our Board, he will remain as one of ISCOs largest shareholders and an active consultant to the Board and executive management and will continue to represent the Company as Chairman Emeritus in a variety of public and private venues.

According to Mr. Aldrich, In my view, Dr. Semechkins willingness to commit such a significant amount of capital to ISCO at the market price of the Companys stock on the date of his offer represents a major vote of confidence in ISCOs future by its most senior executive. We are thankful to Dr. Semechkin for his support that will further advance ISCOs parthenogenetic stem cell-based therapeutic programs and income generating businesses.

Having a majority of independent directors on our companys Board represents an important step in ISCOs development and in transforming ISCO into a leading public company in the field of regenerative medicine.

I want to thank Mr. Aldrich for his long-standing dedication and continued involvement in guiding the Company, said Dr. Semechkin. This long-term investment, along with the new executive management team recruited over the previous twelve months, will provide ISCO with the necessary economic stability and resources to pursue its goals of consolidating our leadership position and accelerating our therapeutic programs, continued Dr. Semechkin.

About International Stem Cell Corporation

International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). HpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenic, homozygous stem cell line that can be a source of therapeutic cells with minimal immune rejection after transplantation into hundreds of millions of individuals of differing genders, ages and racial backgrounds. This offers the potential to create the first true stem cell bank, UniStemCell. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology, and cell-based skin care products through its subsidiary Lifeline Skin Care. More information is available at http://www.internationalstemcell.com.

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International Stem Cell Corporation Completes $5 Million Financing and Elects Jim Berglund to the Board of Directors

Repairing mutations in human mitochondria

LOS ANGELES Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears today in the peer-reviewed journal Proceedings of the National Academy of Sciences.

The current study builds on previous work published in 2010 in the peer-reviewed journal Cell, in which Teitell, Carla Koehler, a professor of chemistry and biochemistry and a Broad stem cell research center scientist, and their team uncovered a role for an essential protein that acts to shuttle RNA into the mitochondria, the energy-producing "power plant" of a cell.

Mitochondria are described as cellular power plants because they generate most of the energy supply within a cell. In addition to supplying energy, mitochondria also are involved in a broad range of other cellular processes including signaling, differentiation, death, control of the cell cycle and growth.

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria have remained poorly understood.

The study in Cell outlined a new role for a protein called polynucleotide phosphorylase (PNPASE) in regulating the import of RNA into mitochondria. Reducing the expression or output of PNPASE decreased RNA import, which impaired the processing of mitochondrial genome-encoded RNAs. Reduced RNA processing inhibited the translation of proteins required to maintain the mitochondrial electron transport chain that consumes oxygen during cell respiration to produce energy. With reduced PNPASE, unprocessed mitochondrial-encoded RNAs accumulated, protein translation was inhibited and energy production was compromised, leading to stalled cell growth.

The findings from the current study provide a form of gene therapy for mitochondria by compensating for mutations that cause a wide range of diseases, said study co-senior author Koehler.

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Repairing mutations in human mitochondria

Correcting human mitochondrial mutations

Public release date: 12-Mar-2012 [ | E-mail | Share ]

Contact: Kim Irwin kirwin@mednet.ucla.edu 310-206-2805 University of California - Los Angeles Health Sciences

Researchers at the UCLA stem cell center and the departments of chemistry and biochemistry and pathology and laboratory medicine have identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs, a finding with implications for treating a host of mitochondrial diseases.

Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects and aging. There currently are no methods to successfully repair or compensate for these mutations, said study co-senior author Dr. Michael Teitell, a professor of pathology and laboratory medicine and a researcher with the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

Between 1,000 and 4,000 children per year in the United States are born with a mitochondrial disease and up to one in 4,000 children in the U.S. will develop a mitochondrial disease by the age of 10, according to Mito Action, a nonprofit organization supporting research into mitochondrial diseases. In adults, many diseases of aging have been associated with defects of mitochondrial function, including diabetes, Parkinson's disease, heart disease, stroke, Alzheimer's disease and cancer.

"I think this is a finding that could change the field," Teitell said. "We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans."

The study appears March 12, 2012 in the peer-reviewed journal Proceedings of the National Academy of Sciences.

The current study builds on previous work published in 2010 in the peer-reviewed journal Cell, in which Teitell, Carla Koehler, a professor of chemistry and biochemistry and a Broad Stem Cell Research Center scientist, and their team uncovered a role for an essential protein that acts to shuttle RNA into the mitochondria, the energy-producing "power plant" of a cell.

Mitochondria are described as cellular power plants because they generate most of the energy supply within a cell. In addition to supplying energy, mitochondria also are involved in a broad range of other cellular processes including signaling, differentiation, death, control of the cell cycle and growth.

The import of nucleus-encoded small RNAs into mitochondria is essential for the replication, transcription and translation of the mitochondrial genome, but the mechanisms that deliver RNA into mitochondria have remained poorly understood.

Read more:
Correcting human mitochondrial mutations

Biostem U.S., Corporation Appoints Heart Surgeon, Thomas W. Prendergast, M.D. to Its Scientific and Medical Board of …

CLEARWATER, FL--(Marketwire -03/12/12)- Biostem U.S., Corporation (OTCQB: BOSM.PK - News) (Pinksheets: BOSM.PK - News) (Biostem, the Company), a fully reporting public company in the stem cell regenerative medicine sciences sector, announced today the addition of cardiothoracic surgeon Thomas W. Prendergast, M.D. to its Scientific and Medical Board of Advisors (SAMBA).

Biostem CEO, Dwight Brunoehler stated, "The Company is now positioned for growth and international expansion. Adding a world class team of clinical, laboratory, and regulatory experts for our Scientific and Medical Board of Advisors to guide our pursuits is essential. Dr. Prendergast brings a wealth of experience not only in the scientific aspects of stem cell use in regenerative medicine, but also in forging research and international economic development opportunities."

Dr. Prendergast is a busy clinical cardiothoracic surgeon, who performs 200-250 open-heart operations and 5 to 15 heart transplants each year. He is deeply involved in numerous clinical and research activities associated with stem cells and heart repair. He is presently Director of Cardiac Transplantation at Robert Wood Johnson University Hospital in New Brunswick, New Jersey where he holds an Associate Professorship of Surgery at the University of Medicine and Dentistry of New Jersey. In addition to being an active participant in stem cell research program development and teaching medical students and residents, his other interests include medical research funding and humanitarian development of programs for Disabled American Veterans.

Dr. Prendergast received his undergraduate degrees in biophysics and Psychology, as well as his medical degree, at Pennsylvania State University. His general surgery residency was for five years at the University of Massachusetts Medical School. His cardiothoracic surgery training was at the University of Southern California School of Medicine, including the Los Angeles County Medical Center. Subsequent fellowship training included pediatric cardiac surgery at Children's Hospital of LA, along with thoracic transplant fellowships at University of Southern California in Los Angeles and at Temple University Hospital in Philadelphia. He spent three years at the University of Kansas establishing thoracic transplant programs until returning to Temple University Hospital as one of their staff heart and lung transplant surgeons. Subsequent to his time at Temple, he joined up with Newark Beth Israel/St. Barnabas Hospitals, where he assumed directorship as the Chief of Cardiac Transplantation and Mechanical Assistance.

Regarding his appointment to the Biostem U.S. Scientific and Medical Board of Advisors, Dr. Prendergast said, "I am looking forward with excitement to working again with Dwight at Biostem. The expansion plan is sound, well paced, and will afford improved quality of life opportunities to many people around the world."

About Biostem U.S., Corporation

Biostem U.S., Corporation (OTCQB: BOSM.PK - News) (Pinksheets: BOSM.PK - News) is a fully reporting Nevada corporation with offices in Clearwater, Florida. Biostem is a technology licensing company with proprietary technology centered around providing hair re-growth using human stem cells. The company also intends to train and license selected physicians to provide Regenerative Cellular Therapy treatments to assist the body's natural approach to healing tendons, ligaments, joints and muscle injuries by using the patient's own stem cells. Biostem U.S. is seeking to expand its operations worldwide through licensing of its proprietary technology and acquisition of existing stem cell related facilities. The company's goal is to operate in the international biotech market, focusing on the rapidly growing regenerative medicine field, using ethically sourced adult stem cells to improve the quality and longevity of life for all mankind.

More information on Biostem U.S., Corporation can be obtained through http://www.biostemus.com, or by calling Kerry D'Amato, Marketing Director at 727-446-5000.

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Biostem U.S., Corporation Appoints Heart Surgeon, Thomas W. Prendergast, M.D. to Its Scientific and Medical Board of ...