Recent findings by a team of engineering and medical scientists at Stanford University shed new light on how cell components move around and self-renew. Part of the study’s focus was on the link between microtubules and self-organization.

Microtubules, hollow tubes about 25 nm in diameter, are critical for maintaining cell shape and movements. The study analyzed what role microtubules have in maintenance, and found that microtubules are continuously losing and gaining molecules. Understanding the mechanics of how microtubules move around and contribute to regeneration helps to light affordable paths to wound healing in humans and animals.

Cells are known to self-organize at the direction of particular protein structures, via recognized regulators of the organization. However, the Stanford team observed that some cells self-organized in the absence of their known regulators. An interaction between microtubules and other molecules on the membrane surface was the reason.

This observation raised questions about what role microtubules play in the regeneration when other elements of the system are paralyzed. The researchers described how microtubules seemed to be involved in some minimal requirements for cellular self-organization. Identifying this process opens the door to greater understanding of cell renewal.

Clarifying the precise functions of microfluidics has paved the way to viable organoids, on which assessments can be done without having to conduct tests on an entire organism. For example, the University of British Columbia researchers recently were able to architect human vascular organoids that were nurtured to duplicate diabetic blood vessels, and can be used as test models.

The UBC scientists were able to grow human blood vessels as organoids in a lab, for the first time. This spawns investigation of treatments for vascular diseases by highlighting how changes to blood vessels occur. Such changes are a major cause of death among diabetics.

An illustration of vascular organoids, lab-made human blood vessels, based on original data. Credit: IMBA

“Being able to build human blood vessels as organoids from stem cells is a game changer,” said the study’s senior author Josef Penninger. “Every single organ in our body is linked with the circulatory system. This could potentially allow researchers to unravel the causes and treatments for a variety of vascular diseases, from Alzheimer’s disease, cardiovascular diseases, wound healing problems, stroke, cancer and, of course, diabetes.”

Many diabetic symptoms are the result of changes in blood vessels that result in impaired oxygen supply of tissues, and impaired circulation. Not a lot has been known about vascular changes arising from diabetes. This creation of human blood-vessel organoids is a significant step toward tipping the scales from unknowns to knowns.

Determining how to cultivate three-dimensional human blood-vessel organoids in a lab dish is indeed a huge step toward unveiling blood-vessel change mechanisms.

These “vascular organoids” when transplanted into mice, developed into functional human blood vessels, including capillaries and arteries. So not only was it possible to engineer blood-vessel organoids from human stem cells in a dish, but they also grew a functional human vascular system in another species.

The organoids resemble human capillaries to a great extent, even on a molecular level, and can be used to study blood vessel diseases directly on human tissue. The researchers described how organoids can be used to study the lack of oxygen and nutrient delivery to blood vessels that occurs in diabetic patients, causing complications including kidney failure, heart attacks, strokes, blindness, and the peripheral artery disease that leads to amputations.

They were surprised to find the vascular organoids showed expansion of the basement membrane, which is exactly what causes the oxygen-and-nutrient depletion in humans. The damage to the vascular organoids precisely mirrored what is seen in diabetic patients.

Using the vascular organoids for testing, they found that no currently-prescribed anti-diabetic medications had positive effects on these blood vessel defects. But they did find an enzyme inhibitor that prevented thickening of the basement membrane.

The researchers noted that the findings could allow them to identify underlying causes of vascular disease, and to potentially develop and test new treatments for the world’s estimated 420 million people with diabetes.

That many patients should theoretically translate into significant Research and Development endeavors.

Enjoyed this article? Don’t forget to share.

Kathy Jean Schultz

Kathy Jean Schultz is a freelance medical science writer who focuses on medical innovations. She earned a Master’s Degree in Research Methodology from Hofstra University, and a Master’s Degree in Psychology from Long Island University. She is a member of the National Association of Science Writers, and the Association of Health Care Journalists. Her articles about organoids include "Would you trust a 3-D printed mini organ to test your drugs?" and "Stem cells not only slow disease, they come with their own safety test".

• http://kathyjeanschultz.pressfolios.com/

The post Being Able to Build Human Blood Vessels as Organoids from Stem Cells is a Game Changer appeared first on The MicroFluidic Circle.

New research suggests microfluidic factors might also determine whether the stem cell is stressed or not stressed. Stem cells that are growing and developing under stress from radiation treatment were observed to differ from stem cells developing in less-stressed environments— that is, with no radiation. A recent animal study suggests stem cells might be able to switch between a “normal-growth” version of themselves, to a “growth-under-stress” version, if that is what the body needs.

Dr. John Chute, of the UCLA Broad Stem Cell Research Center and a professor of hematology/oncology, investigates differences between the microfluidic environments of normal-growth stem cells, compared to those of growth-under-stress stem cells. The Chute team’s goal is to illuminate why normal-growth cells can switch to become growth-under-stress cells, as reported in a recent Cell Stem Cell article. In a press release, Chute observed that “Although the switch occurs, the reason for the change is a mystery.”

Treatments such as radiation and chemotherapy leave human blood-forming cells dangerously stressed and depleted.  A growth-under-stress version of stem cell treatment might be able to heal that depletion much better than a normal-growth version.

The new findings spur questions about whether it might be possible to predict the stress level of stem cells, and to administer the most effective stem cell treatments to radiation patients, in order to speed recovery.

Just as soil nutrients sustain a plant stem, the microfluidic environment surrounding stem cells nurtures them. According to Chute, “In stem cell research, two important questions are, ‘What are the micro-environment cells that regulate stem cells?’ and ‘How do they do it?’” U.S. National Institutes of Health scientists agree: “Microfluidics offers a systematic way to study the decision-making process of stem cells.” In addition, analyses of stem cells based on the microfluidics that nurture them “can be done in a much deeper and wider way” than without them.

NIH scientists have also observed that it is ultimately their microfluidic complexities that predict how stem cells will become one particular body part or another. To gain a precise understanding of how body-part differentiation happens, microfluidic analyses are a necessity.

That necessity is nowhere more evident than in efforts to find out how switching between normal-growth and growth-under-stress stem cells happens. The possible impact on recovery from cancer treatment could be immense. That impact supports industry analyses that the microfluidics market, for which the 2016 global evaluation was $4.76 billion U.S. dollars, will grow to $12.45 billion by 2025.

Numbers tell the story. A surging biotechnology sector paired with the simultaneously increasing global burdens of disease are estimated to drive up market growth. For example, according to the 2017 World Health Organization data, the number of patients suffering from diabetes worldwide was estimated at 422 million in 2014 — and microfluidic advances contribute to innovative diabetes treatments.

The endless frontier of research targets also points to growth on many fronts, from stem-cell stress levels to brain cells, fibrosis and bone joints.

Currently, some new companies that develop stem cells for brain research — deliverable to scientists in both industry and academia — are gaining clients because many facilities do not have the resources to generate neural stem cells themselves. The new companies assemble stem cell types onto microfluidic chips that duplicate human tissue, as well as predict physiological processes. As their novel production challenges are ironed out, these companies will develop and deliver in short time frames.

As reported in a recent Financial Post article, Canada’s Genomics Application Partnership Program (GAPP) supports collaborations specifically to bridge the gap between research and commercialization, and is now funding a $6.5 million microfluidics project to develop fibrosis treatments.

According to U.S. National Institutes of Health scientists, the limitations of a bone joint and cartilage repair are fueling the development of stem cell therapies for weakened cartilage, and this work relies “upon microfluidic technology.”

Predictions about microfluidic commercialization encompass the fact that there were more than 15.5 million cancer survivors in the U.S. in 2016, and this number might be more than 20 million by 2026. About 7 million U.S. patients have had bone treatments such as hip or knee replacements. By 2030, U.S. cartilage-related knee replacement surgeries are projected to total 3.5 million per year.  More than 70,000 people worldwide live with cystic fibrosis.

Analysts need only to do the math.

Enjoyed this article? Don’t forget to share.

Kathy Jean Schultz

Kathy Jean Schultz is a freelance medical science writer who focuses on medical innovations. She earned a Master’s Degree in Research Methodology from Hofstra University, and a Master’s Degree in Psychology from Long Island University. She is a member of the National Association of Science Writers, and the Association of Health Care Journalists. Her articles about organoids include "Would you trust a 3-D printed mini organ to test your drugs?" and "Stem cells not only slow disease, they come with their own safety test".

• http://kathyjeanschultz.pressfolios.com/

The post Microfluidic Environments Nurture Stem Cells on Their Journey Toward Commercialization appeared first on The MicroFluidic Circle.

Oliver was born with good eyesight, but due to a hereditary condition, over a decade he had gradually lost much of his vision. For years his sight had been worsening until he underwent experimental stem cell surgery in a Florida-based treatment study. His vision loss was reversed by that surgery in 2015. “I went from legally blind to legal-to-drive in eight weeks,” said the Nashville, Tenn., man.

Oliver’s own retinal specialist had described his condition as “incurable” in no uncertain words. Yet days after surgery, “I came out of the surgeon’s office and saw the crisp sparkle of cars in the sun parked in the parking lot. And the leaves on the trees.” And a few months later, he saw his grandchildren’s’ faces for the first time.

According to the World Health Organization, about 36 million people worldwide are blind and 217 million have vision impairment. Fortunately for them, the list of innovative ways microfluidics technology promises to buttress stem cell treatment for blindness is impressive. Microfluidics engineering has the potential to advance the design of tiny systems and procedures to make stem-cell-generated organoids and tissues-on-chips more functional — more like a real human organ, thus advancing understanding of stem cell effectiveness.

Living organs comprise branched vascular networks, and almost all cells are close to a capillary, for sufficiency. Vascularization that delivers oxygen and nutrients to organoids is necessary; during organoids’ early development they were isolated in lab dishes and were therefore by definition diffusion-limited. Control of microfluids within tissue-chips could help to mimic natural human physiology. This is one way that microfluidic engineering might move stem cells’ capabilities forward.

Microchannels can permit fluid flow at real-life rates. Microfluidic devices in tissues-on-chips can innovatively duplicate essential functions of blood vessels for oxygen flow, while also removing waste.

Although much has been demystified by science in recent decades, much is still unknown about how stem cells work. Microfluidic devices may offer a way to study the decision-making process of stem cells. They can imitate the structural physiology of organs and provide a platform for further study. “The Organoid Revolution” seminars at the World Stem Cell Summit in Miami in January 2018 highlighted new developments.

Stem cells have been successfully used in a number of patient-consented, experimental surgeries, internationally as well as in several U.S. National Institutes of Health-sponsored clinical trials. The need for thorough, prudent painstaking research of the highest quality and maintained at rigorous academic standards — a long, slow process — can be at odds with vulnerable people seeking timely access to treatments for any number of serious conditions — especially those who see that stem cell treatment works for others. Microfluidics engineering has the potential to speed understanding of stem cells’ effectiveness and could potentially shorten approval processes, while simultaneously thwarting unethical use.

Doug Oliver, left, President of the Regenerative Outcomes Foundation, recently interviewed Dr. Francis Collins, Director of the U.S. National Institutes of Health, in connection with the World Stem Cell Summit. The interview is one of Oliver’s “Pioneers of Hope” series.
Credit: Regenerative Outcomes Foundation 2017

The vision was restored for Oliver after he was nearly blind for 11 years. His treatment could have been classified as “unproven” by the FDA, although his outcome has been clinically verified, and he is currently undergoing additional testing at the U.S. National Eye Institute. He considers himself living proof of the game-changing benefits of cell therapy. Organoid systems offer one of the most promising platforms for harnessing stem cells’ power.

Doug Oliver now spends much of his time advocating for patients seeking treatment for vision loss and other serious conditions to access clinical trials that might restore their health. In 2016, he founded The Regenerative Outcomes Foundation, to support outcomes research, inspire hope and raise awareness, and provide resources to help smooth the way for patients navigating the bureaucracy of clinical trials. “I want these treatment trials to be available sooner and to more people who have no hope of treatment in the near future,” he says.

FDA approval of drugs requires evidence they are safe and effective, something that historically has cost drug companies millions of dollars and many years of clinical trials to achieve. Some have proposed even longer approval processes to deter unsafe stem cell practitioners offering “snake oil” treatments.

Oliver believed a process could be designed that struck a balance between access for patients and the need for safe and effective treatments for serious conditions, including vision loss. In 2016, the U.S. Congress agreed and enlisted Oliver to help craft the 21^st Century Cures Act. “I wanted these treatment trials to be available sooner and to more people who have no hope of treatment in the near future for blindness,” Oliver says. He guided the Senate HELP Committee in developing FDA procedures that enforce safety while not “suffocating ingenuity the nation needs.”

Ingenuity is exactly where microfluidics research comes in.

Enjoyed this article? Don’t forget to share.

Kathy Jean Schultz

Kathy Jean Schultz is a freelance medical science writer who focuses on medical innovations. She earned a Master’s Degree in Research Methodology from Hofstra University, and a Master’s Degree in Psychology from Long Island University. She is a member of the National Association of Science Writers, and the Association of Health Care Journalists. Her articles about organoids include "Would you trust a 3-D printed mini organ to test your drugs?" and "Stem cells not only slow disease, they come with their own safety test".

• http://kathyjeanschultz.pressfolios.com/

The post Seeing Is Believing: Tissue-Chips on the Quest to End Blindness appeared first on The MicroFluidic Circle.