Stem Cell Clinic

Circadian rhythms regulate skin stem cell metabolism and expansion, study finds

By Uncategorized

UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

Andersen adds that it is possible that future studies could advance therapeutic insights from this research.

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Circadian rhythms regulate skin stem cell metabolism and expansion, study finds

Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

By Uncategorized

Body clock protects cells from metabolism-generated oxygen radical damage during division

Irvine, Calif., Jan. 6, 2015 -- UC Irvine scientists studying the role of circadian rhythms in skin stem cells found that this clock plays a key role in coordinating daily metabolic cycles and cell division.

Their research, which appears Jan. 6 in Cell Reports, shows for the first time how the body's intrinsic day-night cycles protect and nurture stem cell differentiation. Furthermore, this work offers novel insights into a mechanism whereby an out of synch circadian clock can contribute to accelerated skin aging and cancers.

Bogi Andersen, professor of biological chemistry and medicine, and Enrico Gratton, professor of biomedical engineering, focused their efforts on the epidermis, the outermost protective layer of the skin that is maintained and healed by long-lived stem cells.

While the role of the circadian clock in processes such as sleep, feeding behavior and metabolism linked to feeding and fasting are well known, much less is known about whether the circadian clock also regulates stem cell function.

The researchers used novel two-photon excitation and fluorescence lifetime imaging microscopy in Laboratory of Fluorescence Dynamics in UCI's Department of Biomedical Engineering to make sensitive and quantitative measurements of the metabolic state of single cells within the native microenvironment of living tissue.

They discovered that the circadian clock regulates one form of intermediary metabolism in these stem cells, referred to as oxidative phosphorylation. This type of metabolism creates oxygen radicals that can damage DNA and other components of the cell. In fact, one theory of aging posits that aging is caused by the accumulative damage from metabolism-generated oxygen radicals in stem cells.

The Andersen-Gratton study also revealed that the circadian clock within stem cells shifts the timing of cell division such that the stages of the cell division cycle that are most sensitive to DNA damage are avoided during times of maximum oxidative phosphorylation.

Other studies in animals have linked aging to disruption of circadian rhythms, and Andersen said that accelerated aging could be caused by asynchrony in the metabolism and cell proliferation cycles in stem cells.

"Our studies were conducted in mice, but the greater implication of the work relates to the fact that circadian disruption is very common in modern society, and one consequence of such disruption could be abnormal function of stem cells and accelerated aging," he said.

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Circadian rhythms regulate skin stem cell metabolism and expansion, UCI study finds

Gamida Cell treatment granted orphan drug status

By Stem Cell Treatment

Stem cell therapy developer Gamida Cell has been awarded orphan drug status by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for leukemia treatment NiCord. The investigational drug treats acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma and myelodysplastic syndrome (MDS). Gamida Cell intends to file for NiCord orphan drug status with the EMA for other indications as well.

Gamida Cell president and CEO Dr. Yael Margolin said, "Receipt of orphan drug status for NiCord in the US and Europe advances Gamida Cell's commercialization plans a major step further, as both afford significant advantages. We very much appreciate the positive feedback and support of the FDA and EMA and look forward to continuing what has been a very positive dialogue with these important agencies."

The FDA and EMA grant an orphan drug designation to promote the development of products that demonstrate promise for the treatment of rare diseases or conditions. Orphan drug designation provides for various regulatory and economic benefits, including seven years of market exclusivity in the US and 10 years in the EU.

NiCord is derived from a single cord blood unit, which has been expanded in culture and enriched with stem cells using Gamida Cell's proprietary NAM technology. It is currently being tested in a Phase I/II study as an investigational therapeutic treatment for hematological malignancies such as leukemia and lymphoma. In this study, NiCord is being used as the sole stem cell source.

Published by Globes [online], Israel business news - http://www.globes-online.com - on January 6, 2015

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Gamida Cell treatment granted orphan drug status

'CRISPR' science: Newer genome editing tool shows promise in engineering human stem cells

By Stem Cell Medicine

Johns Hopkins study could advance use of stem cells for treatment and disease research

A powerful "genome editing" technology known as CRISPR has been used by researchers since 2012 to trim, disrupt, replace or add to sequences of an organism's DNA. Now, scientists at Johns Hopkins Medicine have shown that the system also precisely and efficiently alters human stem cells.

In a recent online report on the work in Molecular Therapy, the Johns Hopkins team says the findings could streamline and speed efforts to modify and tailor human-induced pluripotent stem cells (iPSCs) for use as treatments or in the development of model systems to study diseases and test drugs.

"Stem cell technology is quickly advancing, and we think that the days when we can use iPSCs for human therapy aren't that far away," says Zhaohui Ye, Ph.D., an instructor of medicine at the Johns Hopkins University School of Medicine. "This is one of the first studies to detail the use of CRISPR in human iPSCs, showcasing its potential in these cells."

CRISPR originated from a microbial immune system that contains DNA segments known as clustered regularly interspaced short palindromic repeats. The engineered editing system makes use of an enzyme that nicks together DNA with a piece of small RNA that guides the tool to where researchers want to introduce cuts or other changes in the genome.

Previous research has shown that CRISPR can generate genomic changes or mutations through these interventions far more efficiently than other gene editing techniques, such as TALEN, short for transcription activator-like effector nuclease.

Despite CRISPR's advantages, a recent study suggested that it might also produce a large number of "off-target" effects in human cancer cell lines, specifically modification of genes that researchers didn't mean to change.

To see if this unwanted effect occurred in other human cell types, Ye; Linzhao Cheng, Ph.D., a professor of medicine and oncology in the Johns Hopkins University School of Medicine; and their colleagues pitted CRISPR against TALEN in human iPSCs, adult cells reprogrammed to act like embryonic stem cells. Human iPSCs have already shown enormous promise for treating and studying disease.

The researchers compared the ability of both genome editing systems to either cut out pieces of known genes in iPSCs or cut out a piece of these genes and replace it with another. As model genes, the researchers used JAK2, a gene that when mutated causes a bone marrow disorder known as polycythemia vera; SERPINA1, a gene that when mutated causes alpha1-antitrypsin deficiency, an inherited disorder that may cause lung and liver disease; and AAVS1, a gene that's been recently discovered to be a "safe harbor" in the human genome for inserting foreign genes.

Their comparison found that when simply cutting out portions of genes, the CRISPR system was significantly more efficient than TALEN in all three gene systems, inducing up to 100 times more cuts. However, when using these genome editing tools for replacing portions of the genes, such as the disease-causing mutations in JAK2 and SERPINA1 genes, CRISPR and TALEN showed about the same efficiency in patient-derived iPSCs, the researchers report.

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'CRISPR' science: Newer genome editing tool shows promise in engineering human stem cells

Scientists Develop Pioneering Method to Define Stages of Stem Cell Reprogramming

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Newswise In a groundbreaking study that provides scientists with a critical new understanding of stem cell development and its role in disease, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Kathrin Plath, professor of biological chemistry, have established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into stem cells that resemble those found in the embryo.

The study was published online ahead of print in the journal Cell.

Induced pluripotent stem cells (known as iPSCs) are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. iPSC cells, however, are generated by reprogramming skin or blood cells and do not require an embryo.

Reprogramming is a long process (about one to two weeks) and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process are also not well understood. This knowledge is important, as iPSCs hold great promise in the field of regenerative medicine, as they can provide a single source of patient-specific cells to replace those lost to injury or disease. They can also be used to create novel disease models from which new drugs and therapies can be developed.

This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy, said Plath. This can ultimately benefit patients with new and better treatments for a wide range of diseases.

Drs. Vincent Pasque and Jason Tchieu, postdoctoral fellows in the lab of Dr. Plath and co-first authors of the study, developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed on a daily basis or every other day the process of transformation at the single-cell level. The data were collected and recorded over a period of up to two weeks.

Plaths team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that importantly, the stages were the same across all the different reprogramming systems and different cell types analyzed.

The exact stage of reprogramming of any cell can now be determined, said Pasque. This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level.

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Scientists Develop Pioneering Method to Define Stages of Stem Cell Reprogramming

Pioneering method developed to define stages of stem cell reprogramming

By Uncategorized

In a groundbreaking study that provides scientists with a critical new understanding of stem cell development and its role in disease, UCLA researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research led by Dr. Kathrin Plath, professor of biological chemistry, have established a first-of-its-kind methodology that defines the unique stages by which specialized cells are reprogrammed into stem cells that resemble those found in the embryo.

The study was published online ahead of print in the journal Cell.

Induced pluripotent stem cells (known as iPSCs) are similar to human embryonic stem cells in that both cell types have the unique ability to self-renew and have the flexibility to become any cell in the human body. iPSC cells, however, are generated by reprogramming skin or blood cells and do not require an embryo.

Reprogramming is a long process (about one to two weeks) and largely inefficient, with typically less than one percent of the primary skin or blood cells successfully completing the journey to becoming an iPSC. The exact stages a cell goes through during the reprogramming process are also not well understood. This knowledge is important, as iPSCs hold great promise in the field of regenerative medicine, as they can provide a single source of patient-specific cells to replace those lost to injury or disease. They can also be used to create novel disease models from which new drugs and therapies can be developed.

"This research has broad impact, because by deepening our understanding of cell reprogramming we have the potential to improve disease modeling and the generation of better sources of patient-specific specialized cells suitable for replacement therapy," said Plath. "This can ultimately benefit patients with new and better treatments for a wide range of diseases.

Drs. Vincent Pasque and Jason Tchieu, postdoctoral fellows in the lab of Dr. Plath and co-first authors of the study, developed a roadmap of the reprogramming process using detailed time-course analyses. They induced the reprogramming of skin cells into iPSC, then observed and analyzed on a daily basis or every other day the process of transformation at the single-cell level. The data were collected and recorded over a period of up to two weeks.

Plath's team found that the changes that happen in cells during reprogramming occur in a sequential stage-by-stage manner, and that importantly, the stages were the same across all the different reprogramming systems and different cell types analyzed.

"The exact stage of reprogramming of any cell can now be determined," said Pasque. "This study signals a big change in thinking, because it provides simple and efficient tools for scientists to study stem cell creation in a stage-by-stage manner. Most studies to date ignore the stages of reprogramming, but we can now seek to better understand the entire process on both a macro and micro level."

Plath's team further discovered that the stages of reprogramming to iPSC are different from what was expected. They found that it is not simply the reversed sequence of stages of embryo development. Some steps are reversed in the expected order; others do not actually happen in the exact reverse order and resist a change until late during reprogramming to iPSCs.

"This reflects how cells do not like to change from one specialized cell type to another and resist a change in cell identity," said Pasque. "Resistance to reprogramming also helps to explain why reprogramming takes place only in a very small proportion of the starting cells."

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Pioneering method developed to define stages of stem cell reprogramming

Brainstorm Stem-Cell Therapy Continues to Show Treatment Effect in ALS Patients

By Stem Cell Treatment

By: Adam Feuerstein | 01/05/15 - 10:52 AM EST

Once injected, the NurOwn stem cells bathe the damaged neurons of ALS patients with secretions of nerve growth factors. Brainstorm has a home run on its hands if NurOwn can be shown to slow or halt the progressive destruction of neurons, and if that disease-modifying effect translates into improved muscle function for ALS patients. Monday's update comes from a Phase IIa trial in which 14 ALS patientswere followed for the three months without treatment. At month four, each patient wastransplanted with their own personalized NurOwn therapy and then assessed every month for six months. Brainstorm evaluated NurOwn's impact on ALS disease progression using the ALSFRS score, a commonly used assessment of treatment response and muscle function in ALS patients. Lung function, another commonly used measure of efficacy in ALS clinical trials, was also measured.

Twelve ALS patients were evaluable for response. Of these, 11 patientsshowed aslowing of ALS disease progression at six months compared to baseline, measured either by improved ALSFRS or lung function scores, Brainstorm said. Two other patients enrolled in the study died. Administration of the NurOwn therapy was well tolerated by patients, the company said.

The final Phase IIa data announced Monday were a small improvement over interim results from the same study presented last June. Further, detailed data from the study will be presented at a medical meeting later this year. For perspective purposes, it's important to note that this phase IIa study enrolled a relatively small number of ALS patients and was conducted at a single hospital in Israel. This doesn't necessarily discredit the positive results, but conclusions about NurOwn's ultimate benefit as an ALS therapy can't be drawnuntil data from larger studies are gathered.

Brainstorm is conducting another, larger Phase II study in the U.S., enrolling 48 ALS patients who will be randomized 3:1 to receive a single NurOwn treatment in the muscle and spine, or a placebo treatment. The study is being conducted at two hospitals in Massachusetts, UMass Medical Center and Massachusetts General, and the Minnesota-based Mayo Clinic. The study's primary endpoint is the safety and tolerability of NurOwn, but investigators will also assess ALS patients for efficacy using measures of ALS disease activity and muscle function. The first patient was enrolled into the Phase II study last June and Brainstorm expects results to be ready in the first half of 2016.

The company is also in the planning stages for another Phase II study in which ALS patients will be treated with multiple doses of NurOwn. Must Read: 11 Best Small-Cap Technology Stocks That Could Hit It Big in 2015

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Brainstorm Stem-Cell Therapy Continues to Show Treatment Effect in ALS Patients

Restore and Regenerate

By Stem Cell Treatment

Some people say that osteoarthritis, cartilage degradation, and chronic joint pains degenerative diseases associated with agingare conditions with no cure, but Dr. Charlie Poblete and Dr. Jae Pak say otherwise.

It is a new era of medicine, opens Dr. Jae Pak, one of Koreas premier orthopedic stem cell surgeons and a visiting expert consultant of the Stem Care Orthopedics Department under Aivee Institute (AI). He was recently in the country to shed light on stem cell therapy and how it offers more accessible treament options for patients suffering from degenerative orthopedic conditions.

Dr. Pak was joined by Dr. Charlie Poblete, one of the countrys leading orthopedic surgeon who has a special interest on regenerative medicine and stem cells. Incidentally, Dr. Poblete is the head of the Stem Care Orthopedic Department of AI. Stem cells are not really part of alternative medicine. Its part of a modern medicine because we are talking about the biochemistry that goes on in the body with stem cell treatment, Dr. Charlie relates while adding, the good thing about medicine nowadays is its starting to look at the molecular aspect of the body, the molecular and cellular side of medicine.

Over the years, stem cell therapy has been touted as one procedure that can heal multitude of bone, cartilage, and joint ailments. Stem cells are the bodys natural healing cells. They are recruited by chemical signals emitted by damaged tissues to repair and regenerate the damaged cells. Stem cells derived from an individuals tissues may well be the next major development in medicine. In the right environment, these stem cells can change into bone, cartilage, muscle, fat, collagen, neural tissue, blood vessels, and even some organs. Stem cells may also effect healing by secreting special chemical messengers that repair damaged tissue.

There are many clinical conditions that benefits from stem cell therapy: heart attack patients have shown quicker healing period, improved condition for patients with multiple sclerosis, muscular dystrophy, Parkinsons disease, ALS, and stroke. Stem cells may also be effective in the treatment of macular degeneration, Crohns disease, and numerous pulmonary conditions. Also, stem cells are now used for patients with kidney failure and in the treatment of critical limb ischemia.

Stem Cell therapy is a simple procedure. Fat is aspirated from the tummy or the thighs, and then we separate the stem cells from them. It is then activated and injected into joints to restore and regenerate, explains Dr. Jae.

Stem Care by The Aivee Group is the countrys pioneer in advanced Autologous Stem Cell Therapy with an esteemed orthopedic team of doctors and surgeons regarded with international qualifications. The institute, with its CEO and medical director Dr. Z. Teo, together with his wife dermatologist Dr. Aivee Teo, now features a stronger multifaceted protocol in treating orthopedic ailments with a faster rate of positive patient response. They are also adept in complimentary therapies to further intensify the restorative powers of stem cells through the effective use of Growth Factors, Shockwave, Radio Frequency, and Electro Magnetic Therapies. 4033245, 4031982, 09209665613, 09175210222. http://www.stemcareinstitute.com

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Restore and Regenerate

The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Orange County, California

By Stem Cell Treatment

Seal Beach, Laguna Hills, and Lake Forest, California (PRWEB) January 05, 2015

The Irvine Stem Cell Treatment Center announces a series of free public seminars on the use of adult stem cells for various degenerative and inflammatory conditions. They will be provided by Dr. Thomas A. Gionis, Surgeon-in-Chief.

The seminars will be held on Sunday, January 11, 2015, at 2:30pm and 4:30pm at Marie Callenders Grill, 12489 Seal Beach Blvd., Seal Beach, CA 90740; Tuesday, January 13, 2015, at 2:00pm and 4:00pm at Pollys Pies, 23701 Moulton Parkway, Laguna Hills, CA 92653; Friday, January 16, 2015, at 1:30pm and 3:30pm at Marie Callenders Grill, 12489 Seal Beach Blvd., Seal Beach, CA 90740; Saturday, January 17, 2015, at 2:30pm and 4:30pm at Dennys Restaurant, 23515 El Toro Road, Lake Forest, CA 92630. Please RSVP at (949) 679-3889.

The Irvine Stem Cell Treatment Center, along with sister affiliates, the Miami Stem Cell Treatment Center and the Manhattan Regenerative Medicine Medical Group, abide by investigational protocols using adult adipose derived stem cells (ADSCs) which can be deployed to improve patients quality of life for a number of chronic, degenerative and inflammatory conditions and diseases. ADSCs are taken from the patients own adipose (fat) tissue (found within a cellular mixture called stromal vascular fraction (SVF)). ADSCs are exceptionally abundant in adipose tissue. The adipose tissue is obtained from the patient during a 15 minute mini-liposuction performed under local anesthesia in the doctors office. SVF is a protein-rich solution containing mononuclear cell lines (predominantly adult autologous mesenchymal stem cells), macrophage cells, endothelial cells, red blood cells, and important Growth Factors that facilitate the stem cell process and promote their activity.

ADSCs are the body's natural healing cells - they are recruited by chemical signals emitted by damaged tissues to repair and regenerate the bodys injured cells. The Irvine Stem Cell Treatment Center only uses Adult Autologous Stem Cells from a persons own fat No embryonic stem cells are used. Current areas of study include: Emphysema, COPD, Asthma, Heart Failure, Parkinsons Disease, Stroke, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, Crohns Disease, and degenerative orthopedic joint conditions. For more information, or if someone thinks they may be a candidate for one of the adult stem cell protocols offered by the Irvine Stem Cell Treatment Center, they may contact Dr. Gionis directly at (949) 679-3889, or see a complete list of the Centers study areas at: http://www.IrvineStemCellsUSA.com.

About the Irvine Stem Cell Treatment Center: The Irvine Stem Cell Treatment Center, along with sister affiliates, the Miami Stem Cell Treatment Center and the Manhattan Regenerative Medicine Medical Group, is an affiliate of the Cell Surgical Network (CSN); we are located in Irvine and Westlake, California. We provide care for people suffering from diseases that may be alleviated by access to adult stem cell based regenerative treatment. We utilize a fat transfer surgical technology to isolate and implant the patients own stem cells from a small quantity of fat harvested by a mini-liposuction on the same day. The investigational protocols utilized by the Irvine Stem Cell Treatment Center have been reviewed and approved by an IRB (Institutional Review Board) which is registered with the U.S. Department of Health, Office of Human Research Protection; and the study is registered with Clinicaltrials.gov, a service of the U.S. National Institutes of Health (NIH). For more information, visit our websites: http://www.IrvineStemCellsUSA.com, http://www.MiamiStemCellsUSA.com or http://www.NYStemCellsUSA.com.

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The Irvine Stem Cell Treatment Center Announces Adult Stem Cell Public Seminars in Orange County, California

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