Stem Cell Research

Team Converts Human Skin Cells Into Embryonic Stem Cells For The First Time

Researchers have now successfully reprogrammed human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body. 

The research breakthrough, led by Shoukhrat Mitalipov, Ph.D., a senior scientist at the Oregon National Primate Research Center (ONPRC), follows previous success in transforming monkey skin cells into embryonic stem cells in 2007. 

The technique used is a variation of a commonly used method called somatic cell nuclear transfer, or SCNT. It involves transplanting the nucleus of one cell, containing an individual’s DNA, into an egg cell that has had its genetic material removed. The unfertilized egg cell then develops and eventually produces stem cells.

Read the entire ONPRC announcement here.

Silk And Cellulose Biologically Effective For Use In Stem Cell Cartilage Repair

Both cellulose and silk are commonly used in textiles but here researchers demonstrate an unexpected use for the two natural polymers when mixed with stem cells.  The team treated blends of silk and cellulose for use as a tiny scaffold that allows adult connective tissue stem cells to form into preliminary form of chondrocytes — the cells that make healthy tissue cartilage — and secrete extracellular matrix similar to natural cartilage. 

“We were surprised with this finding," Dr Wael Kafienah, of Bristol University’s School of Cellular and Molecular Medicine. "The blend seems to provide complex chemical and mechanical cues that induce stem cell differentiation into preliminary form of chondrocytes without need for biochemical induction using expensive soluble differentiation factors. This new blend can cut the cost for health providers and makes progress towards effective cell-based therapy for cartilage repair a step closer.”

Read the Bristol University announcement here.

Brain Region May Hold Key to Aging

“It’s clear from our study that many aspects of aging are controlled by the hypothalamus," said Dongsheng Cai, M.D., Ph.D., professor of molecular pharmacology at Albert Einstein College of Medicine.

"What’s exciting is that it’s possible — at least in mice — to alter signaling within the hypothalamus to slow down the aging process and increase longevity.”

In the current study, Dr. Cai and his team demonstrated that activating the NF-κB pathway in the hypothalamus of mice significantly accelerated the development of aging, as shown by various physiological, cognitive, and behavioral tests. “The mice showed a decrease in muscle strength and size, in skin thickness, and in their ability to learn — all indicators of aging. Activating this pathway promoted systemic aging that shortened the lifespan,” he said.

Conversely, Dr. Cai and his group found that blocking the NF-κB pathway in the hypothalamus of mouse brains slowed aging and increased median longevity by about 20 percent, compared to controls.

Read the full announcement from the Albert Einstein College of Medicine here.

 

Adult Cells Transformed into Early-Stage Neural Progenitor Cells, Bypassing Pluripotent Stem Cell Stage

The absence of iPSC cells rules out the formation of tumors by pluripotent cells in the recipient, a major concern involving stem cell therapy.

A second advance here comes from the virus that delivers genes to reprogram the adult skin cells into a different and more flexible form. Unlike other viruses used for this process, the Sendai virus does not become part of the cell's genes.

"...transplantation experiments confirmed that the reprogrammed cells indeed belong to cells of the intended brain regions and the progenitors produced the three major classes of neural cells: neurons, astrocytes and oligodendrocytes," said Su-Chun Zhang, professor of neuroscience and neurology at the University of Wisconsin-Madison. "This proof-of-principle study highlights the possibility to generate many specialized neural progenitors for specific neurological disorders."

Adapted from the UW-Madison announcement. Read further here.

Stem Cells Found Capable Of Generating New Appetite Regulating Neurons

The new research investigated the hypothalamus looking specifically at the nerve cells that regulate appetite.They established that a population of brain cells called ‘tanycytes’ behave like stem cells and add new neurons to the appetite-regulating circuitry of the mouse brain after birth and into adulthood.

“Until recently we thought that all of these nerve cells were generated during the embryonic period and so the circuitry that controls appetite was fixed," said Dr Mohammad K. Hajihosseini, from the University of East Anglia’s school of Biological Sciences. “Unlike dieting, translation of this discovery could eventually offer a permanent solution for tackling obesity."

Read further in the UEA announcement here.

Antibody Found that Transforms Bone Marrow Stem Cells Directly into Brain Cells

Researchers discovered the method while looking for lab-grown antibodies that can activate a growth-stimulating receptor on marrow cells. One antibody turned out to activate the receptor in a way that induces marrow stem cells--which normally develop into white blood cells--to become neural progenitor cells, a type of almost-mature brain cell.

Changing cells of marrow lineage into cells of neural lineage--a direct identity switch termed "transdifferentiation"--just by activating a single receptor is a noteworthy achievement. Scientists do have methods for turning marrow stem cells into other adult cell types, but these methods typically require a radical and risky deprogramming of marrow cells to an embryonic-like stem-cell state, followed by a complex series of molecular nudges toward a given adult cell fate. Relatively few laboratories have reported direct transdifferentiation techniques.

"As far as I know, no one has ever achieved transdifferentiation by using a single protein--a protein that potentially could be used as a therapeutic," said Richard A. Lerner, the Lita Annenberg Hazen Professor of Immunochemistry and institute professor in the Department of Cell and Molecular Biology at The Scripps Research Institute. "These results highlight the potential of antibodies as versatile manipulators of cellular functions.

Adapted from the TSRI announcement. Read further here.

 

 

Human Embryonic Stem Cells -- Transformed Into Nerve Cells -- Help Mice Regain Ability To Learn and Remember

Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine. "These two neuron types are involved in many kinds of human behavior, emotions, learning, memory, addiction and many other psychiatric issues," said Su-Chun Zhang, professor of neuroscience and neurology at the University of Wisconsin.

The transplanted cells were placed in the hippocampus (an interesting aside: see the release on Neuralstem Inc.'s Phase 1b trial regarding its neurogenic small molecule drug platform for hippocampal regeneration in MDD patients). After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialize and connect to the appropriate cells in the hippocampus.

After the transplant, the mice scored significantly better on common tests of learning and memory in mice.

Read the entire University of Wisconsin announcement here

What Will It Take for Stem Cell Companies to Close the Valuation Gap?: Aliance for Regenerative Medicine’s Chairman Geoff MacKay

One of the major stem cell sector investment questions involves the continued microcap valuation of most of the companies involved as several of them enter or proceed through Phase II clinical trials. Mesoblast of Australia has a valuation of 1.6 billion and has reached 2 billion in the past. No other company has come close, with Osiris and Geron (when Geron was in the stem cell sector) each reaching the 300 to 500 million range at some point along the way. Osiris currently has the highest sector market cap at 325 million, substantially less than Mesoblast. With several companies approaching or reaching the Phase II point in stem cell potential therapies that have shown promise, it is fair to ask when the investment world is going to take serious notice. 

The Julia Group recently interviewed Geoff MacKay  following his recent election as chairman of the board of the Massachusetts Biotechnology Council. MassBio is almost three decades old and is the nation’s oldest biotech trade organization. Mr. MacKay's comments are a very worthwhile read.

Cardiopoietic (Cardiogenically instructed) Stem Cells Shown To Improve Heart Health For Patients Suffering From Heart Failure

"This study helps us move beyond the science fiction notion of stem cell research, providing clinical evidence for a new approach in cardiovascular regenerative medicine, said Andre Terzic, M.D., Ph.D., director of the Mayo Clinic Center for Regenerative Medicine.

In the international stem cell trial, every patient in the stem cell treatment group improved. Heart pumping function improved in each patient within six months following cardiopoietic stem cell treatment. In addition, patients experienced improved fitness and were able to walk longer distances than before stem cell therapy. This is the first application in patients of lineage-guided stem cells for targeted regeneration of a failing organ.

The multi-center, randomized Cardiopoietic stem cell therapy in heart failure (C-CURE) trial involved heart failure patients from Belgium, Switzerland and Serbia. Patients in the control group received standard care for heart failure in accordance with established guidelines. Patients in the cell therapy arm received, in addition to standard care, cardiopoietic stem cells — a first-in-class biotherapeutic. In this process, bone marrow was harvested from the top of the patient's hip, and isolated stem cells were treated with a protein cocktail to replicate natural cues of heart development. Derived cardiopoietic stem cells were then injected into the patient's heart.

Adapted from the Mayo Clinic announcement. Read further here.

 

At Long Last A Method Is Developed to Expand Blood Stem Cells for Bone Marrow Transplant

An expansion of healthy HSCs in the lab would mean that fewer stem cells need to be retrieved from donors. It also suggests that adult blood stem cells could be frozen and banked for future expansion and use — which is not currently possible.

New research has engineered a protein to amplify adult HSCs once they were extracted from the bone marrow of a donor. The engineered protein maintains the expanded HSCs in a stem-like state — meaning, they will not differentiate into specialized blood cell types before they are transplanted in the recipient's bone marrow.

"Our work demonstrates that we can overcome a major technical hurdle in the expansion of adult blood stem cells, making it possible, for the first time, to produce them on an industrial scale,"  said Dr. Pengbo Zhou, professor of pathology and laboratory medicine at Weill Cornell Medical College.

Adapted from the Weill Cornell Medical College announcement. Read further here.

Stem Cells Provide Means Of Culturing New Cartilage To Repair Worn Hips and Knees

New research indicates that cartilage with superior qualities can be grown by cultivating adult stem cells in combination with a small quantity of cells from the patient’s own cartilage.

Nicole Georgi, PhD student at the University of Twente, examined alternatives with the aim of achieving better-quality cartilage after replacement in the body. She took mesenchymal stem cells (MSCs) isolated from bone marrow and let them grow into cartilage. She found that these adult stem cells are good at stimulating the formation of cartilaginous matrix. She also found that the quality of the cartilage thus formed can be improved by growing the MSCs under very low oxygen tension. Cartilage is in a permanent state of low oxygen tension in the body, so this tissue is not perfused. Even better results can be achieved by combining the stem cells with a small number of chondrocytes (cells from cartilage).

Adapted from the University of Twente announcement. Read further here.

Proof Of Principal Induced Neural Progenitor Stem Cell Solution To Parkinson's Disease

For the first time, researchers have transplanted neural cells derived from a monkey's skin into its brain and watched the cells develop into several types of mature brain cells.

In the research, iPS cells were converted into neural progenitor cells. The intermediate-stage cells have the ability to further specialize into  neurons that carry nerve signals, and glial cells that perform support and nutritional functions. This final stage of maturation occurred inside the three rhesus monkeys used in the experiment.

The rhesus monkeys used in the study at the Wisconsin National Primate Research Center had a lesion in a brain region that causes the movement disorder Parkinson's disease, which afflicts up to 1 million Americans. Parkinson's is caused by the death of a small number of neurons that make dopamine, a signaling chemical used in the brain.

Adapted from the University of Wisconsin announcement. Read further here.