June 6, 2017 ISkin (three-dimensional cultured skin) derived from human iPSCs. Immunohistochemical analysis with antibodies to KERATIN 14 (KRT14), p63, cytokeratins (Pan-CK), involucrin, laminin 5, loricrin, KRT10, and filaggrin. The multilayered epidermis expressed KRT14, involucrin, laminin 5, Pan-CK, loricrin, KRT10, and filaggrin in iSkin, indicating that iPSC-keratinocytes terminally differentiate in the skin equivalents. Scale bar is 100 m. Credit: Kazuhiro Kajiwara.

Myelomeningocele is a severe congenital defect in which the backbone and spinal canal do not close before birth, putting those affected at risk of lifelong neurological problems. In a preclinical study published June 6th in Stem Cell Reports, researchers developed a stem cell-based therapy for generating skin grafts to cover myelomeningocele defects before birth. They first generated artificial skin from human induced pluripotent stem cells (iPSCs), and then successfully transplanted the skin grafts into rat fetuses with myelomeningocele.

"We provide preclinical proof of concept for a fetal therapy that could improve outcomes and prevent lifelong complications associated with myelomeningoceleone of the most severe birth defects," says senior study author Akihiro Umezawa of Japan's National Research Institute for Child Health and Development. "Since our fetal cell treatment is minimally invasive, it has the potential to become a much-needed novel treatment for myelomeningocele."

Myelomeningocele, which is the most serious and common form of spina bifida, is a neural tube defect in which the bones of the spine do not completely form. As a result, parts of the spinal cord and nerves come through the open part of the spine. A baby born with this disorder typically has an open area or a fluid-filled sac on the mid to lower back. Most children with this condition are at risk of brain damage because too much fluid builds up in their brains. They also often experience symptoms such as loss of bladder or bowel control, loss of feeling in the legs or feet, and paralysis of the legs.

Babies born with myelomeningocele usually undergo surgery to repair the defect within the first few days of life. Some highly specialized centers also offer intrauterine surgery to close the defect before the baby is born. Although prenatal surgery can improve later neurological outcomes compared with postnatal surgery, it is also associated with higher rates of preterm birth and other serious complications, underscoring the need for safe and effective fetal therapies.

To address this problem, Umezawa and his team set out to develop a minimally invasive approach for generating and transplanting skin grafts that could cover large myelomeningocele defects earlier during pregnancy, potentially improving long-term outcomes while reducing surgical risks. In particular, they were interested in using iPSC technology, which involves genetically reprogramming patients' cells to an embryonic stem cell-like state and then converting these immature cells into specialized cell types found in different parts of the body. This approach avoids ethical concerns while offering the advantages of a potentially unlimited source of various cell types for transplantation, as well as minimal risk of graft rejection by the immune system.

In the new study, the researchers first generated human iPSCs from fetal cells taken from amniotic fluid from two pregnancies with severe fetal disease (Down syndrome and twin-twin3 transfusion syndrome). They then used a chemical cocktail in a novel protocol to turn the iPSCs into skin cells and treated these cells with additional compounds such as epidermal growth factor to promote their growth into multi-layered skin. In total, it took approximately 14 weeks from amniotic fluid preparation to 3D skin generation, which would allow for transplantation to be performed in humans during the therapeutic window of 28-29 weeks of gestation.

Next, the researchers transplanted the 3D skin grafts into 20 rat fetuses through a small incision in the uterine wall. The artificial skin partially covered the myelomeningocele defects in eight of the newborn rats and completely covered the defects in four of the newborn rats, protecting the spinal cord from direct exposure to harmful chemicals in the external environment. Moreover, the engrafted 3D skin regenerated with the growth of the fetus and accelerated skin coverage throughout the pregnancy period. Notably, the transplanted skin cells did not lead to tumor formation, but the treatment significantly decreased birth weight and body length.

"We are encouraged by our results and believe that our fetal stem cell therapy has great potential to become a novel treatment for myelomeningocele," Umezawa says. "However, additional studies in larger animals are needed to demonstrate that our fetal stem cell therapy safely promotes long-term skin regeneration and neurological improvement."

Explore further: Prenatal stem cell treatment improves mobility issues caused by spina bifida

More information: Stem Cell Reports, Kajiwara et al.: "Fetal therapy model of myelomeningocele with three-dimensional skin using amniotic fluid cell-derived induced pluripotent stem cells" http://www.cell.com/stem-cell-reports/fulltext/S2213-6711(17)30220-5 , DOI: 10.1016/j.stemcr.2017.05.013

Journal reference: Stem Cell Reports

Provided by: Cell Press

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3-D skin made of stem cells treats backbone birth defect in rodents - Medical Xpress

RenovaCare is developing breakthrough technologies to address Americas $45 billion wound and burn treatment market. Our flagship CellMist System makes use of a patients own stem cells, which are sprayed onto wounds using our novel SkinGun device.

For patients suffering severe burns and other wounds, the prospect of a quick-healing, gentle spray containing their own stem cells will be a promising alternative to conventional skin graft surgery, which can be painful, prone to complications, and slow-to-heal. Based on preliminary case studies, CellMist System patients can be treated within 90 minutes of arriving in an emergency room; a patients stem cells are isolated, processed, and sprayed on to wound sites for rapid healing.

Preliminary investigational use in Europe and the United States indicate the potential efficacy and safety of RenovaCares technologies. Clinical observations point to the potential for regeneration of new skin in as little as four days, rather than the many weeks of painful and risky recovery required by traditional skin graft techniques. These technologies are the result of nearly a decade of ongoing research and development dedicated to finding the most effective way to access the regenerative properties of a patients own skin stem cells, and the most efficient way to deliver these potent cells to heal moderate to severe skin wounds. We believe that RenovaCares CellMist System and SkinGun spray device are the worlds most advanced technologies of their kind.

This device system requires further clinical evaluation and data collection prior to submission of a premarketing application to the US FDA. At this time it is an investigational system and is not available for general use or sales in the United States.

The CellMist System RenovaCares CellMist System is comprised of two components:

Wikipedia indicates that so far the skin gun treatment has been used exclusively with second degree burns, though there is strong evidence that the treatment will be successful in treating a variety of skin wounds and skin disorders. Patients with infected wounds or with delay in wound healing are suitable for cell grafting treatment. Third-degree burns, however, completely deprive victims of both their epidermis and dermis skin levels, which exposes the tissue surrounding the muscles. The skin gun has not progressed to the point where it can be used for such advanced wounds, and these patients must seek more traditional treatment methods. The skin gun is generally not used for burn victims with anything less than a second-degree burn either. First degree-burns still maintain portions of the epidermis and can readily heal on their own, thus they do not need this expensive technology.

Currently, the skin guns applications have not been extended to include the regeneration of skin lost due to other injuries or skin diseases. It is also limited in that it is only effective immediately following the burn incident.

The average healing time for patients with second degree burns is three to four weeks. This is reduced to a matter of days with skin gun treatment

Traditional skin grafting can be risky, in that chances for infection are relatively high. The skin gun alleviates this concern because the increased speed in which the wound heals directly correlates to the decreased time the wound can be vulnerable to infection. Because of the rapid re-epithelialization associated with skin gun treatment, harmful side effects that can result from an open wound are significantly reduced. Applying the skin cells is quick and doesnt harm the patient because only a thin layer of the patients healthy skin is extracted from the body into the aqueous spray. The electronic spray distributes the skin cells uniformly without damaging the skin cells, and patients feel as if they are sprayed with salt water.

Because the skin cells are actually the patients own cells, the skin that is regenerated looks more natural than skin grown from traditional methods. During recovery, the skin cells grow into fully functional layers of the skin, including the dermis, epidermis, and blood vessels.[17] The regenerated skin leaves little scarring. The basic idea of optimizing regenerative healing techniques to damaged biological structures demonstrated by the skin gun in the future may also be applied to engineering reconstruction of vital organs, such as the heart and kidneys.

There are major limitations: the method will not work on deep burns that go through bone and muscle, specifically below the dermis. As of 2011, only several dozen patients have been treated; it remains an experimental, not a proven, method. As of 2011, the skin gun was still in its prototyping stage, since it has only treated a dozen patients in Germany and the US, compared to over 50,000 treated with Dermagraft bioengineered skin substitute. There is thus a lack of published peer reviewed clinical evidence, and no knowledge of long-term stability of the newly generated skin

Skingun Procedure

There is a seven page review of the skingun at the International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

Skingun Procedure Initially stamp-sized healthy skin of the injured patient is taken and stem cells were collected from it. Then they are harvested by using suitable enzymes. The prepared cell suspension is injected into sterile syringe and inserted into the gun. This gun helps in uniform spreading of the cells on wound. These cells will migrate, multiple, and differentiate forming a new tissue. The complete process occurs with in 2 hr. Full regeneration of skin occurs in 2 weeks and complete formation of texture tools 2-3 months

Stage 1

The CellMist Solution is a liquid suspension containing a patients own regenerative skin stem cells. A small sample (as little as a square inch) of the patients skin is quickly processed to liberate the stem cells from surrounding tissue. The resulting product is referred to as the CellMist Solution. The CellMist Solution is placed in the SkinGun for spray application onto the patients wound.

The CellMist Solution, containing the patients stem cells, is transferred to the SkinGun. The SkinGun sprays the cells onto wound sites to begin healing. Unlike conventional aerosol and pump systems, our next-generation fluid sprayer does not expose fragile cells to strong forces that can tear them apart. Instead our SkinGun gently delivers the CellMist Solution directly to the wound site using a positive-pressure air stream.

SOURCES RenovaCare, Wikipedia, International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

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Stem cells delivered via Skin gun can reduce second degree ...

New skin begins to regenerate as soon as 4 days after this has been sprayed on patients, compared to skin grafting surgery which may take weeks of pain and possible infections.

Patients who suffer from burn wounds and scars that cant heal on their own only have 1 option: skin graft surgery. This can be very painful, and usually leads to several other complications, and it takes forever to actually heal.

However, RenovaCare has developed a new breakthrough piece of tech: CellMist, a gun that sprays stem cells into a patients burn wound, effectively allowing healthy skin to grow out of it.

It works literally like we described it as. Within 90 minutes of a patient being brought to the emergency room, they stem cells are isolated, processed, put in a liquid suspension, and then loaded into the CellMist gun. CellMist then gently sprays the stem cells onto the patients burn wound.

Tests conducted in Europe and the US have shown that new skin begins to regenerate as soon as 4 days after its been sprayed on patients, compared to skin grafting surgery which may take weeks of pain and possible infections.

Source: Next Big Future

So far, CellMist has only been used to treat second degree burns. However, evidence has shown that it can be used for other skin wounds and skin disorders. They dont think itll work for third degree burns though, as this kind of burn wound has damaged the entire epidermis and dermis levels. CellMist isnt advanced enough to heal such a deep burn wound, and victims would unfortunately have to stick to more traditional methods of treatment. First degree burn wounds on the other hand only barely touch the epidermis, meaning it can still heal on its own, thus not needing such an expensive piece of technology.

It is good to note that even though there is evidence that it might be able to heal things other than burns, CellMist wasnt built to regenerate skin lost from other kinds of injuries or diseases. Its also pretty limited, because as we stated earlier, it should be used immediately after the burn incident has occurred, or else it wont work.

Its still a pretty handy invention. The reason why skin grafting is so risky is because it involves cutting the skin open and leaving it open for 3-4 weeks. This means that nasty bacteria and fungi can easily get into the open wound within that time, causing several infections and complications.

Source: Next Big Future

With CellMist, however, simply involves extracting a thin layer of the patients healthy skin and stem cells and turning it into a spray, and then distributing the stem cells into the burn wound evenly, without damaging other healthy skin cells. The healing time only takes a few days, so there is little chance for an infection to occur if treated properly. And since the patients own skin cells are used in the process, the regenerated skin looks much more natural, with only little scarring. The stem cells grow into fully functioning layers of skin, from the dermis, to the epidermis, to even blood vessels.

Hopefully, this cool new invention will make way for other forms of stem cell treatments for the reconstruction of other organs, like ones heart and kidneys.

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Deccan Chronicle

Next Big Future

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This Stem Cell Gun Helps Burn Victims Grow New Skin Faster - GineersNow (press release) (registration) (blog)

In experiments in mice, UC San Francisco researchers have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell generally associated with controlling inflammation,directly trigger stem cells in the skin to promote healthy hair growth. Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back, saidMichael Rosenblum, M.D., an assistant professor of dermatology at UCSF and senior author on the new paper. This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

The new study published online May 26 inCell suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said. Since the same stem cells are responsible for helping heal the skin after injury, the study raises the possibility that Tregs may play a key role in wound repair as well.

Normally Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, we may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help with wound healing into adulthood.

Rosenblum, who is both an immunologist and a dermatologist, wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery. We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

In the new research, led by UCSF postdoctoral fellow and first authorNiwa Ali,several lines of evidence suggested that Tregs play a role in triggering hair follicle regeneration.

First, imaging experiments revealed that Tregs have a close relationship with the stem cells that reside within hair follicles and allow them to regenerate: the number of active Tregs clustering around follicle stem cells typically swells by three-fold as follicles enter the growth phase of their regular cycle of rest and regeneration. Also, removing Tregs from the skin blocked hair regrowth only if this was done within the first three days after shaving a patch of skin, when follicle regeneration would normally be activated. Getting rid of Tregs later on, once the regeneration had already begun, had no effect on hair regrowth.

Tregs role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation, the researchers found. Instead, they discovered that Tregs trigger stem cell activation directly through a common cell-cell communication system known as the Notch pathway. First, the team demonstrated that Tregs in the skin express unusually high levels of a Notch signaling protein called Jagged 1 (Jag1), compared to Tregs elsewhere in the body. They then showed that removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein restored Notch signaling in the stem cells and successfully activated follicle regeneration.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work, Rosenblum said. Now the stem cells rely on the Tregs completely to know when its time to start regenerating.

Rosenblum said the findings may have implications for alopecia areata, an autoimmune disease that interferes with hair follicle regeneration and causes patients to lose hair in patches from their scalp, eyebrows, and faces. Alopecia is among the most common human autoimmune diseases its as common as rheumatoid arthritis, and more common than type 1 diabetes but scientists have little idea what causes it.

After his team first observed hair loss in Treg-deficient mice, Rosenblum learned that the genes associated with alopecia in previous studies are almost all related to Tregs, and treatments that boost Treg function have been shown to be an effective treatment for the disease. Rosenblum speculates that better understanding Tregs critical role in hair growth could lead to improved treatments for hair loss more generally.

The study also adds to a growing sense that immune cells play much broader roles in tissue biology than had previously been appreciated, said Rosenblum, who plans to explore whether Tregs in the skin also play a role in wound healing, since the same follicle stem cells are involved in regenerating skin following injury.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after its damaged, he said. But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

Niwa Aliof UCSF was the lead author on the new study. Additional authors were Bahar Zirak,Robert Sanchez Rodriguez, Mariela L. Pauli,Hong-An Truong, Kevin Lai,Richard Ahn, Kaitlin Corbin, Margaret M. Lowe, PharmD,Tiffany C. Scharschmidt, M.D., Keyon Taravati, Madeleine R. Tan,Roberto R. Ricardo-Gonzalez, M.D., Audrey Nosbaum, M.D.,Wilson Liao, M.D., andAbul K. Abbas, MBBS, of UCSF; Frank O. Nestle, M.D., of Kings College London; Marta Bertoliniand Ralf Paus, M.D., of the University of Mnster in Germany; and George Cotsarelis, M.D., of the University of Pennsylvanias Perelman School of Medicine.

The work was primarily supported by the U.S. National Institutes of Health (K08-AR062064, DP2-AR068130, R21-AR066821), the Burroughs Wellcome Fund, a Scleroderma Research Foundation grant, the National Psoriasis Foundation and the Dermatology Foundation.

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A new baldness treatment? | University of California - University of California

Physicist Stephen Hawking is perhaps the most famous sufferer of motor neuron disease, a crippling degenerative condition that affects an estimated 150,00 people around the world.

Karwai Tang / Getty

In news that may bring hope to Stephen Hawking and hundreds of thousands of others around the world, British scientists have used reprogrammed skin cells to study the development of motor neuron disease.

Its like changing the postcode of a house without actually moving it, explains neuroscientist Rickie Patani, referring to research offering startling new insights into the progress and treatment of the crippling degenerative condition, also known as amyotrophic lateral sclerosis (ALS).

Patani, together with colleague Sonia Gandhi, both from the Francis Crick Institute and University College London, in the UK, led a team of researchers investigating how the disease destroys the nerve cells that govern muscle movement.

The results, published in the journal Cell Reports, comprise the most fine-grained work to date on how ALS operates on a molecular level and suggest powerful new treatment methods based on stem cells.

Indeed, so exciting are the implications of the research that Ghandi and Patani are already working with pharmaceutical companies to develop their discoveries.

The neurologists uncovered two key interlinked interactions in the development of motor neuron disease, the first concerning a particular protein, and the second concerning an auxiliary nerve cell type called astrocytes.

To make their findings, the team developed stem cells from the skin of healthy volunteers and a cohort carrying a genetic mutation that leads to ALS. The stem cells were then guided into becoming motor neurons and astrocytes.

We manipulated the cells using insights from developmental biology, so that they closely resembled a specific part of the spinal cord from which motor neurons arise, says Patani.

We were able to create pure, high-quality samples of motor neurons and astrocytes which accurately represent the cells affected in patients with ALS."

The scientists then closely monitored the two sets of cells healthy and mutated to see how their functioning differed over time.

The first thing they noted was that a particular protein TDP-43 behaved differently. In the patient-derived samples TDP-43 leaked out of the cell nucleus, catalysing a damaging chain of events inside the cell and causing it to die.

The observation provided a powerful insight into the molecular mechanics of motor neuron disease.

Knowing when things go wrong inside a cell, and in what sequence, is a useful approach to define the critical molecular event in disease, says Ghandi.

One therapeutic approach to stop sick motor neurons from dying could be to prevent proteins like TDP-43 from leaving the nucleus, or try to move them back.

The second critical insight was derived from the behaviour of astrocytes, which turned out to function as a kind of nursemaid, supporting motor neuron cells when they began to lose function because of protein leakage.

During the progression of motor neuron disease, however, the astrocytes like nurses during an Ebola outbreak eventually fell ill themselves and died, hastening the death of the neurons.

To test this, the team did a type of mix and match exercise, concocting various combinations of neurons and astrocytes from healthy and diseased tissue.

They discovered that healthy astrocytes could prolong the functional life of ALS-affected motor neurons, but damaged astrocytes struggled to keep even healthy motor neurons functioning.

The research reveals both TDP-43 and astrocytes as key therapeutic targets, raising the possibility that the progress of ALS might be significantly slowed, or perhaps even halted.

Our work, along with other studies of ageing and neurodegeneration, would suggest that the cross-talk between neurons and their supporting cells is crucial in the development and progression of ALS, says Patani.

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Patients' stem cells point to potential treatments for motor | Cosmos - Cosmos

Friday November 20 2009

Human embryonic stem cells

Stem cells could create new skin to help burn victims, BBC News reported. It said that French researchers have duplicated the biological steps that occur during skin formation in embryos. This could potentially provide an unlimited source of temporary skin replacements for burn victims while they wait for grafts from their own skin.

The study in mice behind this report used human embryonic stem cells to make keratinocytes (the most common cell types in the skin). These cultured cells were used to create skin equivalents, which grew successfully when they were grafted onto the backs of mice.

This well-conducted research has potentially developed a successful method of culturing tissue in the laboratory that resembles human skin. Only human trials of the technology will show whether such grafts will be accepted (i.e. not rejected by human patients) as permanent transplants or can provide a temporary skin replacement before grafting.

The research was carried out by Dr Hind Guenou and colleagues from the Institute for Stem Cell Therapy and Exploration of Monogenic disease, and BIOalternatives SAS in France along with colleagues in Madrid. The research was funded by the Institut National de la Sant et de la Recherche Mdicale, University Evry Val dEssonne, Association Franaise contre les Myopathies, Fondation Ren Touraine, and Genopole. The authors declare that they have no conflicts of interest and say that the funders had no role in the studys design, analysis or write-up.

The research was published in thepeer-reviewed medical journal the Lancet.

BBC News has covered this research in a balanced way, pointing out that thiswas animal research and that human studies will follow.

This well-conducted research involved laboratory and animal research which investigated whether epidermal stem cells could be cultured in the laboratory and used in skin grafts.

Burn patients are often treated using autologous skin grafts. These involve a section of healthy skin being removed from another part of the body to harvest the patients own skin cells for culture. A graft for the burn site is produced from this culture. There is a delay of about three weeks between the harvesting of the skin and the graft to allow the cells to grow. During this time, the patient is at risk of dehydration and infection.

Having a ready source of skin cells for temporary grafts while patients are waiting for their autologous grafts would improve the outcome of treatment. With this in mind, the researchers investigated whether keratinocytes (the major cell constituent of the outer layer of the skin, or epidermis) could be derived from human embryonic stem cells.

The researchers began by culturing embryonic stem cells in a specialised medium that encourages cell differentiation (the process whereby cells become specialised). Embryonic stem cells can renew themselves and also have the potential to develop into any type of specialised cell.

Cultures of human embryonic stem cells were then grown on a framework made of fibroblast cells and collagen (a fibrous protein that can form a mesh-like structure) made by fibroblasts. Fibroblasts are the cells that form the underlying structure of tissues and are involved in healing.

The stem cells were manipulated so that they developed into epidermal cells, and monitored throughout their specialisation process to make sure the cells were developing into skin cells. The researchers named the cells keratinocytes derived from human embryonic stem cells (K-hESCs).

After several rounds of subculturing and replication, the cells could be frozen and used in further experiments. Bioengineered skin equivalents were then created by growing the K-hESCs on an artificial matrix. These were then grafted onto the backs of five six-week-old immunodeficient female mice. After 10 to 12 weeks, samples were taken from the implants for analysis.

The researchers confirmed thatthe embryonic stem cells differentiated into keratinocytes, which could be grown in culture medium and which replicated well. These derived skin cells were structurally and functionally similar to normal skin cells in that they could be grown on an artificial matrix using classic techniques.

After 12 weeks of growth on immunodeficient mice, the grafted epidermis had developed into a structure that was consistent with mature human skin.

The researchers concluded that their findings build on previous research and show that K-hESCs can develop into a multi-layer epithelium. This epithelium resembles normal human skin both in cell cultures (in vitro) and following grafting onto live animals (in vivo).

They say that growing human skin from human embryonic stem cells could provide an unlimited resource for temporary skin replacement in patients with large burns who are waiting for autologous skin grafts.

If it can be demonstrated that it works in humans, this technology could improve outcomes for burns patients. The researchers report that the first human trial is currently underway.

At present, skin from deceased donors is used to treat burns patients while they wait for their own skin transplant, but there are often problems with rejection. The researchers highlight several potential benefits of an epidermis reconstructed using K-hESCs, including:

It is important to note that, at present, the researchers are only investigating this technology for providing temporary grafts. They say that whether it can be used for permanent grafts for patients who cant use their own cells needs further investigation. They say that for temporary use, the grafts would only be used for the three-week period while the patients permanent graft is grown.

This is a good study and the findings are exciting in this field, but only human research will tell whether it will have a wider application in the treatment of burns patients.

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Skin grafts from stem cells - NHS

One giant photo looks like a cocoon enmeshed in strands of silk. Another, like a distant nebula as seen by the Hubble Space Telescope. A third brings to mind rivulets of lava pouring down the sides of a volcano atnight.

Yet all of the images in Toronto artist Radha Chaddahs latest exhibition show the same thing: adult-human stem cells that have been reprogrammed to change from skin into neural tissue. The overall effect is similar to taking a voyage through a world that is both utterly exotic yet intimately related to thevoyager.

These are the most striking pictures for me, said Ms. Chaddah, directing attention to a photo in which a cell has been carefully prepared to reveal its cytoskeleton a network of protein fibres that helps maintain shape and function. People dont generally think of cells as having an internalarchitecture.

The Fall.

Courtesy of ArtaGallery

This is not the classic microscope view of the cell, familiar to anyone who has cracked open a high-school biology textbook. Often, the images do not show cell membranes or other recognizable components. Instead, they highlight the hidden structures within cells, which Ms. Chaddah tags with fluorescent antibodies and then blasts with a laser so they glow with vivid colour at the moment she captures the photo. Once the photo is taken, Ms. Chaddah can never go back. So intense are the exposures she requires, that her tiny subjects are destroyed in the act of imagingthem.

Researchers are keen to exploit the potential of stem cells because they can be induced to switch identity. This property holds tremendous promise for regenerative medicine. For example, in the future, a patients skin cells may be reprogrammed and used to help restore ailing vision due to a deterioratingretina.

This is the kind of possibility that Ms. Chaddah was helping to explore when she was a graduate student in cell and molecular biology a decade ago, eventually publishing her work on stem cells in the Journal ofNeuroscience.

Exodus.

courtesy of ArtaGallery

But, like the cells that fascinate her, Ms. Chaddah found herself changing identities. She had started off with training in fine arts and art conservation before going back to school to become a stem-cell researcher. After completing her masters degree, she turned to the arts again, this time with science as herinspiration.

Her current exhibition, which has been on display in Toronto as part of the annual Contact photography festival, is the product of a meeting of those two worlds. As a graduate student, she needed to repeatedly image the cells she was working with a laborious and frequently frustrating process that could sometimes produce results that were beautiful to look at even when they werent scientificallyusable.

I would go into that little microscope room and be lost in there for five or six hours, she said. Then Id come out with zero data, a major headache and a few amazingpictures.

Regents.

Courtesy of ArtaGallery

Recognizing the visual potential of the technique, Ms. Chaddah made a deal with her supervisor, University of Toronto stem-cell scientist Derek van der Kooy: In exchange for some additional research she conducted in the lab, she was given access to the microscope to pursue herart.

I think its a great idea because we look at these cells under the microscope and they look fantastic to us, but they should be fantastic to everyone, Dr. van der Kooysaid.

He added that while he was delighted to see Ms. Chaddahs images appreciated as art, he wished there was more about the science behind them in the exhibition. Ms. Chaddah has taken a less direct route, sparking the viewers curiosity by giving the images biblical titles a choice that is also meant to draw attention to the way medical discoveries can be viewed with something approaching religious reverence. While stem cells are the subject of legitimate research, they have also spurred the desperate to seek miracle treatments based on questionableevidence.

Genesis.

Courtesy of ArtaGallery

Yet, there is also plenty to feed a sense of wonder at the machinery of life. In a piece called Exodus, which is also the name of the exhibition, Ms. Chaddah has captured a neural cell in the act of migration a reminder, she said, that when human cells are cultured in a Petri dish they can revert to acting as individuals rather than as part of a larger organism. On another level, it also refers to the new world of medical benefits and risks that the manipulation of cells is leading us to as asociety.

But even without such layers of meaning, Ms. Chaddah said she is often surprised by the sense of connection her images seem to evoke, even when visitors are not entirely sure what they are looking at as they wander into thegallery.

Its interesting how many people stand amazed in front of these things and they have some feeling that it has something to do with them even before they read that it came from human skin, she said. I want to draw people in with beauty but I would love it if people would think beyond thebeauty.

Covenant.

Courtesy of ArtaGallery.

Exodus is on display until May 31 at the Arta Gallery, 14 Distillery Lane, Toronto, as part of the Scotiabank Contact PhotographyFestival.

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Toronto artist exposes the hidden architecture of cells - The Globe ... - The Globe and Mail

In experiments in mice, UC San Francisco researchers have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell generally associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth. Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

"Our hair follicles are constantly recycling: when a hair falls out, the whole hair follicle has to grow back, said Michael Rosenblum, MD, PhD, an assistant professor of dermatology at UCSF and senior author on the new paper. This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

The new study published online May 26 in Cell suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said. Since the same stem cells are responsible for helping heal the skin after injury, the study raises the possibility that Tregs may play a key role in wound repair as well.

Anti-Inflammatory Immune Cells Activate Skin Stem Cells

Normally Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, we may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help with wound healing into adulthood.

Rosenblum, who is both an immunologist and a dermatologist, wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery. We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

In the new research, led by UCSF postdoctoral fellow and first author Niwa Ali, PhD, several lines of evidence suggested that Tregs play a role in triggering hair follicle regeneration.

First, imaging experiments revealed that Tregs have a close relationship with the stem cells that reside within hair follicles and allow them to regenerate: the number of active Tregs clustering around follicle stem cells typically swells by three-fold as follicles enter the growth phase of their regular cycle of rest and regeneration. Also, removing Tregs from the skin blocked hair regrowth only if this was done within the first three days after shaving a patch of skin, when follicle regeneration would normally be activated. Getting rid of Tregs later on, once the regeneration had already begun, had no effect on hair regrowth.

Tregs role in triggering hair growth did not appear related to their normal ability to tamp down tissue inflammation, the researchers found. Instead, they discovered that Tregs trigger stem cell activation directly through a common cell-cell communication system known as the Notch pathway. First, the team demonstrated that Tregs in the skin express unusually high levels of a Notch signaling protein called Jagged 1 (Jag1), compared to Tregs elsewhere in the body. They then showed that removing Tregs from the skin significantly reduced Notch signaling in follicle stem cells, and that replacing Tregs with microscopic beads covered in Jag1 protein restored Notch signaling in the stem cells and successfully activated follicle regeneration.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work, Rosenblum said. Now the stem cells rely on the Tregs completely to know when its time to start regenerating.

Relevance to Autoimmune Hair Loss Rosenblum said the findings may have implications for alopecia areata, an autoimmune disease that interferes with hair follicle regeneration and causes patients to lose hair in patches from their scalp, eyebrows, and faces. Alopecia is among the most common human autoimmune diseases its as common as rheumatoid arthritis, and more common than type 1 diabetes but scientists have little idea what causes it.

After his team first observed hair loss in Treg-deficient mice, Rosenblum learned that the genes associated with alopecia in previous studies are almost all related to Tregs, and treatments that boost Treg function have been shown to be an effective treatment for the disease. Rosenblum speculates that better understanding Tregs critical role in hair growth could lead to improved treatments for hair loss more generally.

The study also adds to a growing sense that immune cells play much broader roles in tissue biology than had previously been appreciated, said Rosenblum, who plans to explore whether Tregs in the skin also play a role in wound healing, since the same follicle stem cells are involved in regenerating skin following injury.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after its damaged, he said. But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

This article has been republished frommaterialsprovided byUCSF. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Ali, N., Zirak, B., Rodriguez, R. S., Pauli, M. L., Truong, H., Lai, K., . . . Rosenblum, M. D. (2017). Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation. Cell. doi:10.1016/j.cell.2017.05.002

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Regulatory T Cells Play Essential Role in Hair Growth - Technology Networks

For the first time, scientists have discovered that a common type of immune cell directly triggers stem cells in the skin that are responsible for hair growth in mice. Without this trigger, hair follicles just don't do their job -even if they have the stem cells necessary to proceed.

As the mechanisms for hair growth in mice are similar in humans, the researchers hope their newly uncovered mechanism could lead to a better understanding of conditions like alopecia, and other types of baldness.

Among the various immune system players we have in the body, there's a subclass of immune cells called regulatory T cells, or Tregs for short.

The vast majority of Tregs live in our lymph nodes, where they help to control inflammation throughout the body. But we also have subsets of Tregs that reside in other body parts, such as muscle or lung tissue.

And studies are starting to show that these 'tissue-resident' Tregs may be performing unique roles specific to the part of body they're in.

Researchers know that both mice and humans have a lot of Tregs in the skin, but so far we know very little about their function there.

Seeing that skin-specific Tregs tend to sit around hair follicles, a team led by researchers from the University of California San Francisco (UCSF) investigated the hypothesis that these immune cells were somehow involved in hair growth.

What they discovered is not just involvement, but a direct trigger - making Tregs a super-important part of the hair growth process.

"Our hair follicles are constantly recycling: when a hair falls out, a portion of the hair follicle has to grow back," senior researcher Michael Rosenblum said in a press statement.

"This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential."

In mammals, hair follicles regenerate in a specific pattern, cycling between growth phases (known as anagen) and rest phases (telogen).

The team tracked the amount of Tregs in the skin of mice during these different phases of hair growth, and found a tight correlation - in the telogen phase these immune cells were much more abundant.

What's more, highly active Tregs were crowding around hair follicles at three times the normal rate, right towards the end of the hair growth rest phase.

Intrigued by this correlation, the scientists took a step further to uncover the biological mechanism involved in the relationship between Tregs and the stem cells that make hair follicles do their job.

To do this, they took genetically modified mice whose Treg cells could be 'knocked out' with a simple intervention.

The researchers clipped the hair on the mice's backs and then applied a depilatory cream for 30 seconds - when you depilate the skin, hair follicles kick into the active hair growth phase.

They monitored the hair regrowth for 14 days, comparing the regrowth between control mice and the ones whose Tregs they had tampered with.

In mice whose Tregs were knocked out in the first three days after depilation, the hair just didn't grow back, leaving them with a bald patch on their backs.

A closer look revealed that Tregs directly trigger the activation of stem cells in the hair follicle through a well-known cell communication mechanism called the Notch signalling pathway, which involves a specific protein called Jag1.

They even found that when they replaced Tregs with microscopic beads covered in Jag1, it triggered the activity in the hair follicles just like Tregs would.

"It's as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work," Rosenblum said.

"Now the stem cells rely on the Tregs completely to know when it's time to start regenerating."

It's a really elegant demonstration of a previously unknown mechanism for hair growth in mice, but there's a lot more work to be done before we can tell whether defective skin Tregs could be the culprits behind hair loss in humans.

But there's at least one tantalising clue that the study is onto something here. In genome-wide association studies of alopecia areata, a condition characterised by 'patchy' hair loss, researchers have found mutations on genes that are involved in Treg function.

Next up, the researchers are hoping to expand their results and investigate how Tregs in the skin could be involved in wound healing, and also various hair loss conditions in humans.

"It will be important to determine whether this principle extends to human diseases of epithelial dysfunction and whether Tregs can be exploited to develop new therapies for stem-cell-mediated tissue regenerative disorders," they write in the study.

These new results are also an exciting addition to the growing body of knowledge scientists have about hair growth. Earlier this month, researchers reported the discovery of a protein that causes skin stem cells to develop into hair cells in mice. They are now investigating whether this protein is involved in hair loss in people.

The research has been published in Cell.

More:
We now have the first evidence that immune cells in the skin directly ... - ScienceAlert

The late actor Telly Savalas said it best: Were all born bald, baby.

And bald CAN be beautiful.

But for many follicly-challenged folks, news out of UC San Francisco this week offers some hope of finally having a bad hair day.

In experiments in mice, researchers there have discovered that regulatory T cells (Tregs; pronounced tee-regs), a type of immune cell associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth.

Without these immune cells as partners, the researchers found, the stem cells cannot regenerate hair follicles, leading to baldness.

Our hair follicles are constantly recycling: when a hair falls out, the whole hair follicle has to grow back, said Dr. Michael Rosenblum, an assistant professor of dermatology at UCSF and senior author on the new paper.

This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential. If you knock out this one immune cell type, hair just doesnt grow.

In other words: no Tregs, no tresses.

The new study appeared online Friday in Cell, a journal that publishes peer-reviewed articles reporting findings of unusual significance in any area of experimental biology.

For 35 million U.S. men and 21 million women who are experiencing hair loss, according to Statistic Brain Research Institute,the UCSF report would probably qualify as significant.

The study suggests that defects in Tregs could be responsible for alopecia areata, a common autoimmune disorder that causes hair loss, and could potentially play a role in other forms of baldness, including male pattern baldness, Rosenblum said.

And since the same stem cells are responsible for helping heal the skin after injury, the researchers note, the study raises the possibility that Tregs may play a key role in wound repair as well.

Normally, the researchers say, Tregs act as peacekeepers and diplomats, informing the rest of the immune system of the difference between friend and foe. When Tregs dont function properly, people may develop allergies to harmless substances like peanut protein or cat dander, or suffer from autoimmune disorders in which the immune system turns on the bodys own tissues.

Like other immune cells, most Tregs reside in the bodys lymph nodes, but some live permanently in other tissues, where researcher say they seem to have evolved to assist with local metabolic functions as well as playing their normal anti-inflammatory role. In the skin, for example, Rosenblum and colleagues have previously shown that Tregs help establish immune tolerance to healthy skin microbes in newborn mice, and these cells also secrete molecules that help heal wounds into adulthood.

Rosenblum wanted to better understand the role of these resident immune cells in skin health. To do this, he and his team developed a technique for temporarily removing Tregs from the skin. But when they shaved patches of hair from these mice to make observations of the affected skin, they made a surprising discovery.

We quickly noticed that the shaved patches of hair never grew back, and we thought, Hmm, now thats interesting, Rosenblum said. We realized we had to delve into this further.

The researchers including UCSF postdoctoral fellow and first author Niwa Ali believe a betterunderstanding of Tregs critical role in hair growth could lead to improved treatments for hair loss more generally and have implications for alopecia areata, an autoimmune disease that causes patients to lose hair in patches from their scalp, eyebrows, and faces.

For many other baldly confident folks, however, Fridays findings may just warrant a shrug.As they say, No hair, dont care.

Here is the original post:
Baldness treatment discovered at UCSF - The Mercury News

The new research showed that adult stem cells could help beat heart failure.

A sticking plaster made from adult stem cells could be a significant step towards combatting heart failure, scientists say.

Researchers discovered that stem cells taken from a patients thigh and transplanted onto the heart led to improved heart function after one year.

Heart failure is thought to affect between 500,000 to 900,000 people in the UK. It occurs when the heart becomes too weak to efficiently pump blood around the body.

The authors of the study, published in the Journal of the American Heart Association, said the therapy was potentially a long-term solution to the problem.

They said that, promising results in the safety and functional recovery warrant further clinical follow-up and larger studies, which they hope will confirm the treatments potential.

Professor Metin Avkiran, associate medical director at the British Heart Foundation, hailed the exciting breakthrough.

He said: Heart failure is a cruel and debilitating illness affecting more than half a million people across the UK. Currently, heart failure is incurable, but stem cell-based treatments may offer new hope to people suffering from the disease.

He echoed the call for further research, saying: The study involved only a small number of patients. In order to establish the long-term safety and benefits of the exciting new treatment we would need larger studies.

Heart failure often leaves sufferers struggling for breath and exhausted while carrying out simple everyday tasks, such as eating or getting dressed.

It can be caused by several issues including heart disease, diabetes and high blood pressure, but can also be the result of an unhealthy lifestyle.

Earlier this month, it was revealed that a remarkable new technique allows adult stem cells to be used to treat burn victims.

Taking a sample of skin stem cells and spraying them onto a victims burn caused new layers of skin to form over the burn, potentially healing even severe burns within weeks.

And in January, scientists released findings showing that synthetic cardiac stem cells could be used to treat patients who had suffered a heart attack by repairing the heart muscle damage.

Originally posted here:
Stem cell 'plaster' could help heart failure patients - The Christian Institute

A new cause of baldness has been accidentally discovered by scientists in the US in a breakthrough that could help develop a way to regrow hair.

The researchers were investigating the role played by anti-inflammatory immune cells called Tregs in skin health generally.

They found a way to temporarily remove the Tregs from the skin of laboratory mice, who had been shaved to allow the effects to be observed.

But the scientists then noticed something unexpected the hairfailed to grow back.

Previously it was thought that stem cells cause hairs to regrow after they fall out, but the team discoveredthat this only happens if Tregs are present.

One of the scientists, Professor Michael Rosenblum, an immunologist and dermatologist at University of California San Francisco, said: Our hair follicles are constantly recycling. When a hair falls out, the whole hair follicle has to grow back.

This has been thought to be an entirely stem cell-dependent process, but it turns out Tregs are essential.

If you knock out this one immune cell type, hair just doesn't grow.

Its as if the skin stem cells and Tregs have co-evolved, so that the Tregs not only guard the stem cells against inflammation but also take part in their regenerative work.

The stem cells rely on the Tregs completely to know when it's time to start regenerating.

The researcher believe that defects in Tregs could be responsible for the immune disease, alopecia areata, which causes hair to fall out in patches and possibly also play a part in other kinds of baldness.

The same stem cells that regrow hair are also involved in healing damage to the skin, so Tregs may also be involved in this process.

Tregs role as previously understood was mainly to regulate the immune system, helping it tell what to attack and what to leave alone.

When they malfunction it can lead to allergies to peanuts and other harmless substances or cause the immune system to attack the body.

Professor Rosenblum and colleagues had previously showed that Tregs help the immune systems of baby mice learn which skin microbes are not harmful and also that they secrete molecules that help heal wounds.

They were investigating these effects further when they noticed that patches of shaved hair on the lab mice were not regrowing.

We thought, Hmm, now thats interesting, Professor Rosenblum said. We realised we had to delve into this further.

Using sophisticated imaging techniques, the researchers were able to show that Tregs gathered around follicle stem cells at the start of the process to regrow a hair.

When Tregs were removed from the skin, this prevented the regrowth of hair but only if this was done within three days of the hair being shaved. After this time, the hair would regrow normally despite the absence of Tregs.

The cause of alopecia is poorly understood, but previous studies have showed genes associated with the condition are mostly related to Tregs. Boosting Treg function has been found to help.

Professor Rosenblum suggested further research into Tregs role could lead to improved treatments for hair loss generally and better understanding of their role in wound healing.

We think of immune cells as coming into a tissue to fight infection, while stem cells are there to regenerate the tissue after it's damaged, he said.

But what we found here is that stem cells and immune cells have to work together to make regeneration possible.

The research was described in the journal Cell.

See the original post here:
New baldness cause accidentally discovered by scientists could lead to hair loss treatment - The Independent

May 24, 2017 by Collene Ferguson Jeff Biernaskies research identifies a factor essential for dermal stem cells to continuously divide during tissue regeneration. Credit: Riley Brandt, University of Calgary

Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskie's research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

"This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin," says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary'sFaculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Children's Hospital Research Institute.

"What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle."

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored byRaquel Gonzalez and Garrett Moffatt,shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you don't have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

"It's an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth" says Biernaskie.

Biernaskie's lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

Explore further: Using stem cells to grow new hair

More information: Raquel Gonzlez et al. Platelet-derived growth factor signaling modulates adult hair follicle dermal stem cell maintenance and self-renewal, npj Regenerative Medicine (2017). DOI: 10.1038/s41536-017-0013-4

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Read more from the original source:
Researchers identify 'signal' crucial to stem cell function in hair follicles - Medical Xpress

Stem cell researchers at the University of Calgary have found another piece of the puzzle behind what may contribute to hair loss and prevent wounds from healing normally.

Jeff Biernaskies research, published recently in the scientific journal npj Regenerative Medicine identifies a key signalling protein called platelet-derived growth factor (PDGF). This protein is critical for driving self-renewal and proliferation of dermal stem cells that live in hair follicles and enable their unique ability to continuously regenerate and produce new hair.

This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin, says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary's Faculty of Veterinary Medicine, and Calgary Firefighters Burn Treatment Society Chair in Skin Regeneration and Wound Healing. Biernaskie is also a member of the Alberta Childrens Hospital Research Institute.

What we show is that in the absence of PDGF signalling hair follicle dermal stem cells are rapidly diminished because of their inability to generate new stem cells and produce sufficient numbers of mature dermal cells within the hair follicle.

Biernaskie and his team of researchers study dermal stem cells located within hair follicles. They are looking to better understand dermal stem cell function and find ways to use these cells to develop novel therapies for improved wound healing after injury, burns, disease or aging.

This study, co-authored by Raquel Gonzalez and Garrett Moffatt, shows that PDGF is key to maintaining a well-functioning stem cell population in skin. And in normal skin, if you dont have enough of it the stem cell pools start to shrink, meaning eventually the hair will no longer grow and wounds will not heal as well.

Its an important start in terms of how we might modulate these cells towards developing future therapies that could regenerate new dermal tissue or maintain hair growth says Biernaskie.

Biernaskies lab is looking at the potential role of stem cells in wound healing and the potential to stimulate these cells to improve skin regeneration, as opposed to forming scars.

The research is funded by a grant from Canadian Institutes for Health Research (CIHR) and the Calgary Firefighters Burn Treatment Society.

This article has been republished frommaterialsprovided bythe University of Calgary. Note: material may have been edited for length and content. For further information, please contact the cited source.

The rest is here:
'Signal' Crucial to Stem Cell Function in Hair Follicles Identified - Technology Networks

Beauty elicits a deep, instinctive need to share from an early age. In fact, we defy you to find a more generous creature than a 7-year-old with a sparkly, new lip gloss in her backpack. Cooties be damned, she will prettify every second grader in sight. And we get it: weve built careers on swapping beauty secrets (and, okay, maybe a gloss or two).

We see this same communal spirit, shall we say, within the industry. Across brands and categories, this borrowing of ideas and technologies sparks trends and spawns knock-offs. In 2017, cosmetic ingredients flow freely, breaking all boundaries: Those once reserved for creams find their way into compacts . The same earthy clay and charcoal that purify pores can also whiten teeth and degrease roots.

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And were all for spreading the love when the science is legit. But the latest take-over hair-care companies co-opting buzzy skin-care actives, like peptides, stem cells, and antioxidants has us questioning just how translatable such technology truly is. Are we going too far in attempting to anti-age and revitalize something thats technicallydead?

Because, facts, after all: While skin and hair are composed of similar proteins and fats, living (innervated, blood-perfused) skin cells are in a constant state of renewal, rising up, plump and fresh, from the basal layer before eventually flattening out and sloughing off, says cosmetic chemist Randy Schueller . When injured or damaged, skin has the capacity to heal itself through normal biological processes, adds cosmetic chemist Jim Hammer . Hair, on the other hand, is dead at least the grown-out lengths of which we see and style and twirl. Hairs only vital part is nestled deep within the scalp: The cells of the hair follicles reproduce rapidly, pushing out hair fibers in the process, explains Melissa Piliang, a dermatologist at the Cleveland Clinic. But once sprouted from the scalp, those strands possess no living cells or repair mechanisms.

These distinctions have long dictated product goals: Skin care aims to affect biological processes, such as boosting cell turnover, increasing collagen synthesis, and inhibiting pigment production, says cosmetic chemist NiKita Wilson. Knowing this, we obsess over penetration can those actives actually get into the skin to do their good work? and chemists devise deep-diving delivery systems and penetration enhancers to guarantee performance. For hair, there really isnt much that can be done on a biological front short of improving the condition of the scalp to promote healthier strands, adds Wilson. It makes sense, then, that the majority of hair potions are designed to work on the surface, moisturizing and sealing hair to make it glassy, smooth, and full, while minimizing friction and breakage. While certain perfectly sized and shaped hydrators and proteins can seep past the hairs outer cuticle layer, into the deeper cortex, says Wilson, their effect is short-lived. Only chemicals like hair dyes and relaxers can alter hair in a lasting way.

So what of these new skin-inspired #hairgoals were hearing about, like anti-aging, anti-pollution, and high-tech hydration? Most of this is marketing driven with maybe a kernel of truth underneath, says Schueller. That kernel could be a single lab test showing a specific active, when dripped on cells in a glass dish, has some sort of effect which, by the way, doesnt mean it will work when delivered in final products on real people, he notes. Or perhaps a company finds a common water contaminant causes some degree of hair damage and then concocts an antioxidant to combat it. Even if the trauma to hair is miniscule compared to ordinary wear and tear, theyve now got enough data to make an antipollution claim and a new line of products to go with it, Schueller says. Across beauty lines, science sells: How do you make hair care more innovative? By using skin-care ingredients that elevate the level of sophistication, says cosmetic chemist Ginger King.

A successful tactic, judging from the proliferation of skin-inspired shampoos and serums on shelves, real and virtual. But why are we so eager to buy? Our population is aging, of course; yearning to maintain a healthy appearance, to look as young as we feel, says psychologist and marketing consultant Vivian Diller, PhD. Any product that promotes youth, well being, and vitality will be enormously appealing.

According to Rachel Anise, a communication studies professor at Golden West College in Huntington Beach, CA, there may also be social-psychology constructs at work here. People, on the whole, are largely swayed by what she calls the halo effect: We see stem cells, for example, as good at a basic level, and thereby extend their goodness to everything else in which they may be included, even if that reasoning is fundamentally flawed. And then theres the way we process advertising claims, she says, quickly and effortlessly, without thinking critically about them. Instead of questioningif or whyantioxidants may work on hair as they do skin, we'll just see a model with beautiful hair, acknowledge from past experience that antioxidants benefit skin, and automatically make the connection in two seconds, no less that they'll give our hair a youthful edge as well, says Anise.

Lucky for you, beauty analysis is sort of our jam. Here, we reality-check three adapted-for-hair-care claims:

THE CLAIM: Slowing down the aging process

WHAT IT MEANS FOR HAIR: The way hair ages has a lot to do with genetics and overall health, says dermatologist Lindsey Bordone. Hair tends to become finer over time as follicles miniaturize after menopause, she adds. It may turn coarse and brittle, and as pigment production wanes, fade to gray. On the scalp, cell turnover slows, giving rise to oil and flakes. UV rays a main cause of skin aging can degrade hairs proteins and color, but youd need a lot of concentrated sun exposure for that to be a real problem, says Schueller.

WHAT WORKS: Collagen and elastin proteins can cling to hairs surface, plumping and softening but only until your next shampoo. Plant-based stem cells essentially serve as antioxidants, curbing free radical damage, but their ability to thicken hair (or skin for that matter) is largely unproven. Surprisingly, peptides, which rev up collagen production, do show promise for aging hair. On the face, they plump skin to delay wrinkles and sagging. When applied to the scalp in a leave-on formula, they aid in anchoring the follicles to help strands remain firmly planted for a thicker head of hair, says Wilson. According to dermatologist Jeannette Graf , peptides are especially beneficial for thinning hair, which results from weakened scalp skin and circulation. Alongside peptides, she suggests looking for essential oils of lavender, orange, sage, and lemon peel to improve microcirculation, and enhance the delivery of nutrients to the hair bulb for healthier strands. As for sun care, hats trump UV filters. Think about how much sunscreen you need to put on skin to truly protect it, Schueller says. Its the same for hair and scalp: Youd need a tremendous amount, and whos going to apply that heavy of a coating?

THE CLAIM: Combatting pollution

WHAT IT MEANS FOR HAIR: Every day, our hair, like our skin, is exposed to free radical-inciting pollutants in the air and water. According to dermatologist Michelle Henry, all types of pollution, including particulate matter, dust, smoke, nickel, lead, and sulfur dioxide and nitrogen dioxide [emitted from vehicles and power plants] can settle on the scalp and hair causing significant inflammation, dryness, dullness, even hair loss.If that werent devastating enough, ground-level smog, which contains high levels of ozone, can bleach our hair color, says Hammer. Other contaminants may rob it completely: Premature graying is seen more in smokers than non-smokers as a result of oxidative stress, says dermatologist Nicole Rogers, adding that free radicals from all sources not just cigarettes can affect the follicles' ability to repigment. That said, pollutions precise toll on hair is unknown. I havent seen a ton of research proving its a major threat, says Schueller. Of all the things that can harm hair chemicals, brushing, heat Id imagine free radicals are low on the list.

WHAT WORKS: With thinning and graying as potential consequences, why take chances? While only a diet rich in free radical-quelching antioxidants can truly defend hair at a follicular level, certain products and practices can help safeguard strands from the environment. For starters, washing your hair thoroughly, and with sufficient frequency for your hair type, is key to curbing the scalp inflammation that contributes to hair loss, says Henry.Shampoos with chelating agents, like EDTA, will gently extract heavy metals (found in car exhaust, cigarette smoke, hard water). Youll also want to look for leave-ins with concentrated doses of antioxidants (think: vitamins, tea extracts, idebenone, resveratrol) to neutralize free radicals, and strand-coating silicones, proteins, and polymers, which provide a physical barrier, walling off hair from pollutants, says Hammer.

THE CLAIM: Healing hydration

WHAT IT MEANS FOR HAIR: With a rich blood supply and an abundance of oil glands, the scalp is an extension of our skin, says dermatologist Francesca Fusco . It shares the same lipids and humectants, and is equally prone to dryness and irritation. Hair suffers from dehydration, too, particularly when its cuticle is eroded (by water, heat, and chemicals).

WHAT WORKS: Hyaluronic acid, a water-binding humectant, and ceramides, moisture-retaining lipids, are both found naturally in the skin (and in countless creams and serums). Since they improve the functioning of skin cells, making them more resilient and efficient, both can help keep the scalp in peak condition. When applied to hair (again, leave-on products work best), they coat strands to lock in moisture while also shielding from heat and styling damage, says Rogers, noting a 2002 study in which ceramides were shown to bind to African hair, helping to reduce breakage. Coconut oil and panthenol (a B vitamin) also nourish the scalp, and unlike most other ingredients, can penetrate inside the hair shaft, hydrating from within to enhance pliability, and keeping the cuticle tight and intact.

Bottom Line: The secret to beautiful hair is a healthy scalp. When the scalp is out of whack meaning theres poor circulation, an oil imbalance, or a build-up of cells we see not only flakes and inflammation, but hair that looks and feels unhealthy, and may even shed before its time, says Fusco. Seek out proven actives that take aim at the scalp (many of which do hail from the skin realm): dandruff-fighting pyrithione zinc (in Doves new DermaCare Scalp collection); clays that absorb excess oil and calm irritation (like those in LOral Paris Extraordinary Clay Pre-Shampoo Mask ); exfoliating salicylic acid or willowbark extract, which keep cells shedding at a normal clip to prevent pile-ups; and the aforementioned hydrators to soothe and replenish dry, depleted follicles.

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knowledge center home stem cell research all about stem cells what are stem cells?

Stem cells are a class of undifferentiated cells that are able to differentiate into specialized cell types. Commonly, stem cells come from two main sources:

Both types are generally characterized by their potency, or potential to differentiate into different cell types (such as skin, muscle, bone, etc.).

Adult or somatic stem cells exist throughout the body after embryonic development and are found inside of different types of tissue. These stem cells have been found in tissues such as the brain, bone marrow, blood, blood vessels, skeletal muscles, skin, and the liver. They remain in a quiescent or non-dividing state for years until activated by disease or tissue injury.

Adult stem cells can divide or self-renew indefinitely, enabling them to generate a range of cell types from the originating organ or even regenerate the entire original organ. It is generally thought that adult stem cells are limited in their ability to differentiate based on their tissue of origin, but there is some evidence to suggest that they can differentiate to become other cell types.

Embryonic stem cells are derived from a four- or five-day-old human embryo that is in the blastocyst phase of development. The embryos are usually extras that have been created in IVF (in vitro fertilization) clinics where several eggs are fertilized in a test tube, but only one is implanted into a woman.

Sexual reproduction begins when a male's sperm fertilizes a female's ovum (egg) to form a single cell called a zygote. The single zygote cell then begins a series of divisions, forming 2, 4, 8, 16 cells, etc. After four to six days - before implantation in the uterus - this mass of cells is called a blastocyst. The blastocyst consists of an inner cell mass (embryoblast) and an outer cell mass (trophoblast). The outer cell mass becomes part of the placenta, and the inner cell mass is the group of cells that will differentiate to become all the structures of an adult organism. This latter mass is the source of embryonic stem cells - totipotent cells (cells with total potential to develop into any cell in the body).

In a normal pregnancy, the blastocyst stage continues until implantation of the embryo in the uterus, at which point the embryo is referred to as a fetus. This usually occurs by the end of the 10th week of gestation after all major organs of the body have been created.

However, when extracting embryonic stem cells, the blastocyst stage signals when to isolate stem cells by placing the "inner cell mass" of the blastocyst into a culture dish containing a nutrient-rich broth. Lacking the necessary stimulation to differentiate, they begin to divide and replicate while maintaining their ability to become any cell type in the human body. Eventually, these undifferentiated cells can be stimulated to create specialized cells.

Stem cells are either extracted from adult tissue or from a dividing zygote in a culture dish. Once extracted, scientists place the cells in a controlled culture that prohibits them from further specializing or differentiating but usually allows them to divide and replicate. The process of growing large numbers of embryonic stem cells has been easier than growing large numbers of adult stem cells, but progress is being made for both cell types.

Once stem cells have been allowed to divide and propagate in a controlled culture, the collection of healthy, dividing, and undifferentiated cells is called a stem cell line. These stem cell lines are subsequently managed and shared among researchers. Once under control, the stem cells can be stimulated to specialize as directed by a researcher - a process known as directed differentiation. Embryonic stem cells are able to differentiate into more cell types than adult stem cells.

Stem cells are categorized by their potential to differentiate into other types of cells. Embryonic stem cells are the most potent since they must become every type of cell in the body. The full classification includes:

Embryonic stem cells are considered pluripotent instead of totipotent because they do not have the ability to become part of the extra-embryonic membranes or the placenta.

A video on how stem cells work and develop.

Although there is not complete agreement among scientists of how to identify stem cells, most tests are based on making sure that stem cells are undifferentiated and capable of self-renewal. Tests are often conducted in the laboratory to check for these properties.

One way to identify stem cells in a lab, and the standard procedure for testing bone marrow or hematopoietic stem cell (HSC), is by transplanting one cell to save an individual without HSCs. If the stem cell produces new blood and immune cells, it demonstrates its potency.

Clonogenic assays (a laboratory procedure) can also be employed in vitro to test whether single cells can differentiate and self-renew. Researchers may also inspect cells under a microscope to see if they are healthy and undifferentiated or they may examine chromosomes.

To test whether human embryonic stem cells are pluripotent, scientists allow the cells to differentiate spontaneously in cell culture, manipulate the cells so they will differentiate to form specific cell types, or inject the cells into an immunosuppressed mouse to test for the formation of a teratoma (a benign tumor containing a mixture of differentiated cells).

Scientists and researchers are interested in stem cells for several reasons. Although stem cells do not serve any one function, many have the capacity to serve any function after they are instructed to specialize. Every cell in the body, for example, is derived from first few stem cells formed in the early stages of embryological development. Therefore, stem cells extracted from embryos can be induced to become any desired cell type. This property makes stem cells powerful enough to regenerate damaged tissue under the right conditions.

Tissue regeneration is probably the most important possible application of stem cell research. Currently, organs must be donated and transplanted, but the demand for organs far exceeds supply. Stem cells could potentially be used to grow a particular type of tissue or organ if directed to differentiate in a certain way. Stem cells that lie just beneath the skin, for example, have been used to engineer new skin tissue that can be grafted on to burn victims.

A team of researchers from Massachusetts General Hospital reported in PNAS Early Edition (July 2013 issue) that they were able to create blood vessels in laboratory mice using human stem cells.

The scientists extracted vascular precursor cells derived from human-induced pluripotent stem cells from one group of adults with type 1 diabetes as well as from another group of healthy adults. They were then implanted onto the surface of the brains of the mice.

Within two weeks of implanting the stem cells, networks of blood-perfused vessels had been formed - they lasted for 280 days. These new blood vessels were as good as the adjacent natural ones.

The authors explained that using stem cells to repair or regenerate blood vessels could eventually help treat human patients with cardiovascular and vascular diseases.

Additionally, replacement cells and tissues may be used to treat brain disease such as Parkinson's and Alzheimer's by replenishing damaged tissue, bringing back the specialized brain cells that keep unneeded muscles from moving. Embryonic stem cells have recently been directed to differentiate into these types of cells, and so treatments are promising.

Healthy heart cells developed in a laboratory may one day be transplanted into patients with heart disease, repopulating the heart with healthy tissue. Similarly, people with type I diabetes may receive pancreatic cells to replace the insulin-producing cells that have been lost or destroyed by the patient's own immune system. The only current therapy is a pancreatic transplant, and it is unlikely to occur due to a small supply of pancreases available for transplant.

Adult hematopoietic stem cells found in blood and bone marrow have been used for years to treat diseases such as leukemia, sickle cell anemia, and other immunodeficiencies. These cells are capable of producing all blood cell types, such as red blood cells that carry oxygen to white blood cells that fight disease. Difficulties arise in the extraction of these cells through the use of invasive bone marrow transplants. However hematopoietic stem cells have also been found in the umbilical cord and placenta. This has led some scientists to call for an umbilical cord blood bank to make these powerful cells more easily obtainable and to decrease the chances of a body's rejecting therapy.

Another reason why stem cell research is being pursued is to develop new drugs. Scientists could measure a drug's effect on healthy, normal tissue by testing the drug on tissue grown from stem cells rather than testing the drug on human volunteers.

The debates surrounding stem cell research primarily are driven by methods concerning embryonic stem cell research. It was only in 1998 that researchers from the University of Wisconsin-Madison extracted the first human embryonic stem cells that were able to be kept alive in the laboratory. The main critique of this research is that it required the destruction of a human blastocyst. That is, a fertilized egg was not given the chance to develop into a fully-developed human.

The core of this debate - similar to debates about abortion, for example - centers on the question, "When does life begin?" Many assert that life begins at conception, when the egg is fertilized. It is often argued that the embryo deserves the same status as any other full grown human. Therefore, destroying it (removing the blastocyst to extract stem cells) is akin to murder. Others, in contrast, have identified different points in gestational development that mark the beginning of life - after the development of certain organs or after a certain time period.

People also take issue with the creation of chimeras. A chimera is an organism that has both human and animal cells or tissues. Often in stem cell research, human cells are inserted into animals (like mice or rats) and allowed to develop. This creates the opportunity for researchers to see what happens when stem cells are implanted. Many people, however, object to the creation of an organism that is "part human".

The stem cell debate has risen to the highest level of courts in several countries. Production of embryonic stem cell lines is illegal in Austria, Denmark, France, Germany, and Ireland, but permitted in Finland, Greece, the Netherlands, Sweden, and the UK. In the United States, it is not illegal to work with or create embryonic stem cell lines. However, the debate in the US is about funding, and it is in fact illegal for federal funds to be used to research stem cell lines that were created after August 2001.

Medical News Today is a leading resource for the latest headlines on stem cell research. So, check out our stem cell research news section. You can also sign up to our weekly or daily newsletters to ensure that you stay up-to-date with the latest news.

This stem cells information section was written by Peter Crosta for Medical News Today in September 2008 and was last updated on 19 July 2013. The contents may not be re-produced in any way without the permission of Medical News Today.

Disclaimer: This informational section on Medical News Today is regularly reviewed and updated, and provided for general information purposes only. The materials contained within this guide do not constitute medical or pharmaceutical advice, which should be sought from qualified medical and pharmaceutical advisers.

Please note that although you may feel free to cite and quote this article, it may not be re-produced in full without the permission of Medical News Today. For further details, please view our full terms of use

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UCalgary researchers identify 'signal' crucial to stem cell function in hair follicles UCalgary News This is the first study to identify the signals that influence hair follicle dermal stem cell function in your skin, says Biernaskie, an associate professor in comparative biology and experimental medicine at the University of Calgary's Faculty of ... and more »

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UCalgary researchers identify 'signal' crucial to stem cell function in hair follicles - UCalgary News

By 2027 to 2037 scientists will likely be able to create a baby from human skin cells that have been coaxed to grow into eggs and sperm and used to create embryos to implant in a womb.

The process, in vitro gametogenesis, or I.V.G., so far has been used only in mice. But stem cell biologists say it is only a matter of time before it could be used in human reproduction opening up mind-boggling possibilities.

With I.V.G., two men could have a baby that was biologically related to both of them, by using skin cells from one to make an egg that would be fertilized by sperm from the other. Women with fertility problems could have eggs made from their skin cells, rather than go through the lengthy and expensive process of stimulating their ovaries to retrieve their eggs.

IVF (Invitro fertilization) produces 70,000, or almost 2 percent, of the babies born in the United States each year. Worldwide there been more than 6.5 million babies born worldwide through I.V.F. and related technologies.

I.V.G. requires layers of complicated bioengineering. Scientists must first take adult skin cells other cells would work as well or better, but skin cells are the easiest to get and reprogram them to become embryonic stem cells capable of growing into different kinds of cells.

Then, the same kind of signaling factors that occur in nature are used to guide those stem cells to become eggs or sperm.

Last year, researchers in Japan, led by Katsuhiko Hayashi, used I.V.G. to make viable eggs from the skin cells of adult female mice, and produced embryos that were implanted into female mice, who then gave birth to healthy babies.

Nature Reconstitution in vitro of the entire cycle of the mouse female germ line

The female germ line undergoes a unique sequence of differentiation processes that confers totipotency to the egg. The reconstitution of these events in vitro using pluripotent stem cells is a key achievement in reproductive biology and regenerative medicine. Here we report successful reconstitution in vitro of the entire process of oogenesis from mouse pluripotent stem cells. Fully potent mature oocytes were generated in culture from embryonic stem cells and from induced pluripotent stem cells derived from both embryonic fibroblasts and adult tail tip fibroblasts. Moreover, pluripotent stem cell lines were re-derived from the eggs that were generated in vitro, thereby reconstituting the full female germline cycle in a dish. This culture system will provide a platform for elucidating the molecular mechanisms underlying totipotency and the production of oocytes of other mammalian species in culture.

Scientists could make an egg out of skin cells from women who cant produce viable eggsor who have other fertility problems, or who dont want to go through the difficult process of surgical removal of their eggs for IVF. Or men with fertility problems involving their sperm. Two women could make a child that was truly theirs, with eggs from one and sperm made from skin cells of the other. Or two men, vice-versa.

Mouse oocytes created from embryonic stem cells. Credit: Katsuhiko Hayashi, Kyushu Univ

In a couple of decades, Greely predicts, it will be possible to examine and select an embryo not just for a particular genetic disease but also for other traits, ranging from hair color to musical ability to potential temperament.

Greely concedes that Easy PGD will be mostly available in rich countries, but he also thinks it will be widely available in those countries because it will be free. Preventing the birth of people with genes that increase their risk of serious (and expensive) disease will save health care systems so much money that Easy PGD will be convincingly cost-effective.

That will be a powerful incentive to encourage prospective parents to further decouple procreation from sexual intercourse, and make it easy for them to drop off their skin cells at a lab. The lab will then generate a big supply of embryos containing the couples genes, embryos that can be examined for desirable characteristics as well as disease genes. The winner of this elimination contest will, presumably, be selected for implantation.

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Mice embryos from skin cells and by 2037 human embryos from skin cells - Next Big Future

Rio Sugimura

Researchers made these blood stem cells and progenitor cells from human induced pluripotent stem cells.

After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today in Nature1, 2, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature1. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells2.

For many years, people have figured out parts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells into induced pluripotent stem (iPS) cells, which are capable of producing many other cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factors genes that control other genes into the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full life more than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS cells. A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, Bhatia says. I hoped the critics were wrong, and now I know they were.

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Lab-grown blood stem cells produced at last - Nature.com

Nearly 40 years after the world was jolted by the birth of the first test-tube baby, a new revolution in reproductive technology is on the horizon and it promises to be far more controversial than in vitro fertilization ever was.

Within a decade or two, researchers say, scientists will likely be able to create a baby from human skin cells that have been coaxed to grow into eggs and sperm and used to create embryos to implant in a womb.

The process, in vitro gametogenesis, or I.V.G., so far has been used only in mice. But stem cell biologists say it is only a matter of time before it could be used in human reproduction opening up mind-boggling possibilities.

With I.V.G., two men could have a baby that was biologically related to both of them, by using skin cells from one to make an egg that would be fertilized by sperm from the other. Women with fertility problems could have eggs made from their skin cells, rather than go through the lengthy and expensive process of stimulating their ovaries to retrieve their eggs.

It gives me an unsettled feeling because we dont know what this could lead to, said Paul Knoepfler, a stem cell researcher at UC Davis. You can imagine one man providing both the eggs and the sperm, almost like cloning himself. You can imagine that eggs becoming so easily available would lead to designer babies.

Some scientists even talk about what they call the Brad Pitt scenario when someone retrieves a celebritys skin cells from a hotel bed or bathtub. Or a baby might have what one law professor called multiplex parents.

There are groups out there that want to reproduce among themselves, said Sonia Suter, a George Washington University law professor who began writing about I.V.G. even before it had been achieved in mice. You could have two pairs who would each create an embryo, and then take an egg from one embryo and sperm from the other, and create a baby with four parents.

Three prominent academics in medicine and law sounded an alarm about the possible consequences in a paper published this year.

I.V.G. may raise the specter of embryo farming on a scale currently unimagined, which might exacerbate concerns about the devaluation of human life, Dr. Eli Y. Adashi, a medical science professor at Brown; I. Glenn Cohen, a Harvard Law School professor; and Dr. George Q. Daley, dean of Harvard Medical School, wrote in the journal Science Translational Medicine.

Still, how soon I.V.G. might become a reality in human reproduction is open to debate.

I wouldnt be surprised if it was five years, and I wouldnt be surprised if it was 25 years, said Jeanne Loring, a researcher at The Scripps Research Institute in La Jolla who, with the San Diego Zoo, hopes to use I.V.G. to increase the population of the nearly extinct northern white rhino.

Loring said that when she discussed I.V.G. with colleagues who initially said it would never be used with humans, their skepticism often melted away as the talk continued. But not everyone is convinced that I.V.G. will ever become a regularly used process in human reproduction even if the ethical issues are resolved.

People are a lot more complicated than mice, said Susan Solomon, chief executive of the New York Stem Cell Foundation. And weve often seen that the closer you get to something, the more obstacles you discover.

I.V.G. is not the first reproductive technology to challenge the basic paradigm of baby-making. Back when in vitro fertilization was beginning, many people were horrified by the idea of creating babies outside the human body. And yet, I.V.F. and related procedures have become so commonplace that they now account for about 70,000, or almost 2 percent, of the babies born in the United States each year. According to the latest estimate, there have been more than 6.5 million babies born worldwide through I.V.F. and related technologies.

Of course, even I.V.F. is not universally accepted. The Catholic Church remains firm in its opposition to in vitro fertilization, in part because it so often leads to the creation of extra embryos that are frozen or discarded.

I.V.G. requires layers of complicated bioengineering. Scientists must first take adult skin cells other cells would work as well or better, but skin cells are the easiest to get and reprogram them to become embryonic stem cells capable of growing into different kinds of cells.

Then, the same kind of signaling factors that occur in nature are used to guide those stem cells to become eggs or sperm. (Cells taken from women could be made to produce sperm, the researchers say, but the sperm, lacking a Y chromosome, would produce only female babies.)

Last year, researchers in Japan, led by Katsuhiko Hayashi, used I.V.G. to make viable eggs from the skin cells of adult female mice, and produced embryos that were implanted into female mice, who then gave birth to healthy babies.

The process strikes some people as inherently repugnant.

There is a yuck factor here, said Arthur Caplan, a bioethicist at New York University. It strikes many people as intuitively yucky to have three parents, or to make a baby without starting from an egg and sperm. But then again, it used to be that people thought blood transfusions were yucky, or putting pig valves in human hearts.

Whatever the social norms, there are questions about the wisdom of tinkering with basic biological processes. And there is general agreement that reproductive technology is progressing faster than consideration of the legal and ethical questions it raises.

We have come to realize that scientific developments are outpacing our ability to think them through, Adashi said. Its a challenge for which we are not fully prepared. It would be good to be having the conversation before we are actually confronting the challenges.

Some bioethicists take the position that while research on early stages of human life can deepen the understanding of our genetic code, tinkering with biological mechanisms that have evolved over thousands of years is inherently wrongheaded.

Basic research is paramount, but its not clear that we need new methods for creating viable embryos, said David Lemberg, a bioethicist at National University in California. Attempting to apply what weve learned to create a human zygote is dangerous, because we have no idea what were doing, we have no idea what the outcomes are going to be.

Lewin writes for The New York Times.

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