Engineers put the 'squeeze' on human stem cells

Feb 10, 2015 Inside the cell, calcium ions are released from a structure called the endoplasmic reticulum (ER). Forces applied to the bead cause ion channels in the ER to open mechanically (shown in red above), rather through biochemical signaling chemically (shown in green below). Credit: Jie Sun/UC San Diego

After using optical tweezers to squeeze a tiny bead attached to the outside of a human stem cell, researchers now know how mechanical forces can trigger a key signaling pathway in the cells.

The squeeze helps to release calcium ions stored inside the cells and opens up channels in the cell membrane that allow the ions to flow into the cells, according to the study led by University of California, San Diego bioengineer Yingxiao Wang.

Researchers have known that mechanical forces exerted on stem cells have a significant role to play in how the cells produce all kinds of tissuesfrom bone to bloodfrom scratch. But until now, it hasn't been clear how some of these forces translate into the signals that prod the stem cells into building new tissue.

The findings published in the journal eLife could help scientists learn more about "the functional mechanisms behind stem cell differentiation," said Wang, an associate professor of bioengineering. They may also guide researchers as they try to recreate these mechanisms in the lab, to coax stem cells into developing into tissues that could be used in transplants and other therapies.

"The mechanical environment around a stem cell helps govern a stem cell's fate," Wang explained. "Cells surrounded in stiff tissue such as the jaw, for example, have higher amounts of tension applied to them, and they can promote the production of harder tissues such as bone."

Stem cells living in tissue environments with less stiffness and tension, on the other hand, may produce softer material such as fat tissue.

Wang and his colleagues wanted to learn more about how these environmental forces are translated into the signals that stem cells use to differentiate into more specialized cells and tissues. In their experiment, they applied force to human mesenchymal stem cellsthe type of stem cells found in bone marrow that transform into bone, cartilage and fat.

The engineers used a highly focused laser beam to trap and manipulate a tiny bead attached to the cell membrane of a stem cell, creating an optical "tweezers" to apply force to the bead. The squeeze applied by the tweezers was extremely smallon the order of about 200 piconewtons. (Forces are measured in a unit called newtons; one newton is about the weight of an apple held to the Earth by gravity, and one piconewton is equivalent to one-trillionth of a newton.)

When there were no calcium ions circulating outside the cell, this force helped to release calcium ions from a structure inside the cell called the endoplasmic reticulum. The release is aided by the cell's inner structural proteins called the cytoskeleton, along with contracting protein machinery called actomyosin. When the force triggered the movement of calcium ions into the cell from its extracellular environment, only the cytoskeleton was involved, the researchers noted.

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Engineers put the 'squeeze' on human stem cells

The stem-cell miracle is anecdotal

On the weekend, a whos who of hockey legends gathered to pay tribute to Gordie Howe in his hometown of Saskatoon.

In addition to sharing memories about Mr. Hockey, a constant theme of the festivities was his miracle recovery from stroke.

Mr. Howe, 86, suffered two strokes last year and, according to his family, was near death before he travelled to Clinica Santa Clarita in Tijuana, Mexico, in December for experimental stem-cell treatment.

Afterward, Mr. Howe was able to walk again. He regained a lot of weight and he began to resemble his old self. (Most of this is second-hand; Mr. Howe also suffers from dementia and has not or cannot speak of his symptoms or treatment first-hand.)

After his stem-cell treatment, the doctor told us it was kind of an awakening of the body, his son, Marty Howe, told The Canadian Press. They call it the miracle of stem cells and it was nothing less than a miracle.

Mr. Howes Lazarus-like recovery makes for a great tug-at-the-heartstrings narrative for a man whose career has been the embodiment of perseverance and longevity. But if you step back a moment and examine the science, all sorts of alarm bells should go off.

Stem cells, which were discovered in the early 1960s, have the remarkable potential to develop into many different cells, at least in the embryonic stage. They also serve as the bodys internal repair system.

The notion that spinal cords and limbs and heart muscle and brain cells could be regenerated holds a magical appeal.

But, so far, stem-cell therapies have been used effectively to treat only a small number of blood disorders, such as leukemia. (Canada has a public bank that collects stem cells from umbilical-cord blood and a program to match stem-cell donors with needy patients.)

Stem cells also show promise in the treatment of conditions such as spinal-cord injuries, Parkinsons and multiple sclerosis, but those hopes have not yet moved from the realm of science-fiction into clinical medicine.

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The stem-cell miracle is anecdotal

Hoping for a cure

John Wyse, a shellfish farmer and father of three from Nanaimo, has not been able to work due to deteriorating health from a rare form of multiple sclerosis.

image credit: CHRIS BUSH/The News Bulletin

John Wyse, 40, a Nanaimo father of three, is in a race against the progression of his disease.

Wyse was diagnosed in 2010 with primary progressive multiple sclerosis and hopes to receive hematopoietic stem cell transplantation treatment at the Hassadah Medical Centre in Israel.

Multiple sclerosis affects the brain and spinal cord by causing inflammation that damages myelin the protective covering of the nerves and disrupts nerve impulses, giving rise to symptoms that include extreme fatigue, weakness, lack of coordination, impaired sensation, vision and bladder problems, cognitive impairment and mood changes.

What causes MS is unknown, but its thought to be an autoimmune disorder causing the bodys immune system to attack healthy tissue.

Patients suffer repeating cycles of advancing deterioration followed by periods of remission in all forms of MS except for the primary progressive variant of the disease, which progresses without remission and is the only form of MS for which there are no conventional drugs or treatments available.

Research into stem cell transplantation therapy is the latest avenue of hope for successful treatment and a possible cure. Clinics in Germany, Russia, India and Israel currently offer stem cell treatment and clinical trials are also being conducted in Canada, the U.S. and elsewhere.

Most clinical trials and some treatment clinics will not accept primary progressive MS patients.

Wyse, with his wife and three daughters, are trying to raise $158,200 to pay for his treatment in Israel, scheduled for April 2016, but the Hassadah Medical Centre places limits on how far Wyses condition can deteriorate before it will not accept him. Wyse, who now walks with a cane and hasnt been able to work for a year, figures he has little more than a year before hes no longer a treatment candidate.

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Hoping for a cure

Stem cells treatment for chronic pain: What can I expect? (Part 3) – Video

Stem cells treatment for chronic pain: What can I expect? (Part 3)
https://plus.google.com/+ColumbiaPainManagementPCHoodRiver/ (541) 716-6469 What can I expect if I have stem cell treatment for chronic pain due to arthritis? Doctors at Columbia Pain ...

By: Trey Rigert

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Stem cells treatment for chronic pain: What can I expect? (Part 3) - Video

AdiStem — Adult Stem Cells Derived from Adipose Tissue …

Adult Stem Cells (ASCs), by definition, are unspecialized or undifferentiated cells that not only retain their ability to divide mitotically while still maintaining their undifferentiated state but also, given the right conditions, have the ability to differentiate into different types of cells including cells of different germ-origin an ability referred to as transdifferentiation or plasticity.1,2 In vitro, the conditions under which transdifferentiation occurs can be brought about by modifying the culture medium in which the cells are cultured. In vivo, the same changes are seen when the ASCs are transplanted into a tissue environment different to their own tissue-of origin. Though the exact mechanism of this transdifferentiation of ASCs is still under debate, this ability of ASCs along with their ability to self-renew is of great interest in the field of Regenerative Medicine as a therapeutic tool in being able to regenerate and replace dying, damaged or diseased tissue.

Clinically, however, there are a few criteria that ASCs need to fulfill before they can be viewed as a viable option in Regenerative Medicine. These are as follows:3

Adds Millions of Stem Cells Back into Circulation.

Adipose Tissue Yields an Abundance of ASCs

Compared to any other source, the high concentrations of regenerative cells found in adipose tissue (depots of fat for storing energy) especially in the abdominal region, by sheer volume of availability, ensure an abundance in number of ASCs ranging in the millions per unit volume. The sheer number available also has the added advantage of not needing to be cultured in a laboratory over days in order to get the desired number of ASCs to achieve what is called therapeutic threshold i.e. therapeutic benefit. In addition, harvesting ASCs from adipose tissue through simple, minimally invasive liposuction under local anesthesia is relatively easier and painless and poses minimal risk to the patient compared to all other possible methods.

Adipose tissue ASCs (AT-ASCs) are extremely similar to stem cells isolated from bone marrow (BMSCs). The similarities in profile between the two types of ASCs range from morphology to growth to transcriptional and cell surface phenotypes.4,5 Their similarity extends also to their developmental behavior both in vitro and in vivo. This has led to suggestions that adipose-derived stem cells are in fact a mesenchymal stem cell fraction present within adipose tissue.6

Clinically, however, stromal vascular fraction-derived AT-ASCs have the advantage over their bone marrow-derived counterparts, because of their abundance in numbers eliminating the need for culturing over days to obtain a therapeutically viable number and the ease of the harvest procedure itself being less painful than the harvest of bone marrow. This, in theory, means that an autologous transplant of adipose-derived ASCs will not only work in much the same way as the successes shown using marrow-derived mesenchymal stem cell transplant, but also be of minimal risk to the patient.

AT-ASCs, like BM-ASCs, are called Mesenchymal ASCs because they are both of mesodermal germ-origin. This means that AT-ASCs are able to differentiate into specialized cells of mesodermal origin such as adipocytes, fibroblasts, myocytes, osteocytes and chondrocytes.7,8,9 AT-ASCs are also able (given the right conditions of growth factors) to transdifferentiate into cells of germ-origin other than their own. Animal model and human studies have shown AT-ASCs to undergo cardiomyogenic 10, endothelial (vascular)11, pancreatic (endocrine) 12, neurogenic 13, and hepatic trans-differentiation14 , while also supporting haematopoesis15.

Low Risk to the Patient

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AdiStem -- Adult Stem Cells Derived from Adipose Tissue ...