Induced PluriPotent Stem Cells

Some of the first trials to test whether reprogrammed stem cells can repair diseased organs have begun to report positive results. Research teams involved in the studies, all based in Japan, say they provide early hints that the hotly anticipated technology works. But many researchers outside the country are cautious about overstating the significance of the trials, saying they were small and the results have yet to be peer reviewed.

Induced pluripotent stem (iPS) cells are those that have been reprogrammed from mature cells — often taken from the skin — into an embryonic-like state. From there, they can then turn into any cell type and be used to repair damaged organs.

In January, researchers reported in a preprint1 that the first person in Japan given a transplant of heart-muscle cells made from reprogrammed stem cells had experienced improved heart function following the procedure. Then, in April, another group announced that several people’s vision had improved after their diseased corneas were transplanted with corneal cells made from reprogrammed stem cells — a world first.

Ongoing trials are “delivering encouraging first insights into the evolution of iPS-cell-based therapies, from lab to patient”, says Wolfram-Hubertus Zimmermann, a pharmacologist at the University Medical Centre Göttingen in Germany.

The biggest impact of the iPS-cell trials in Japan so far is that they “give people confidence all over the world that it is doable”, says Kapil Bharti, a translational stem-cell researcher at the US National Eye Institute in Bethesda, Maryland.

The iPS-cell field is hugely popular in Japan, in large part because it was a local scientist, Shinya Yamanaka at Kyoto University, who discovered how to make the cells. Expectations for the potential uses of iPS cells soared in 2012, when Yamanaka won the medicine Nobel prize for his 2006 discovery. In 2013, the Japanese government announced that it would pour ¥110 billion (US$814 million today) over the next ten years into regenerative medicine.

In that time, Japanese scientists have launched at least ten trials in people. These have largely shown that the technology is safe, but have yet to establish that it has a beneficial effect. Now, public enthusiasm has waned, which threatens future government funding, says Masayo Takahashi, an ophthalmologist and president of the cell-therapy company Vision Care in Kobe, Japan.

iPS-cell technology has only been around for 16 years. And bringing it into clinical testing has happened unbelievably fast,” says Zimmermann. “The challenge is that this is all happening under high public attention.”

Source: https://www.nature.com/

How to Bioprint Muscles

Researchers at Harvard Medical School and Sichuan University have developed a novel means of 3D bioprinting live human muscle-tendon tissues. As opposed to normal extrusion bioprinting, which involves depositing cells along X and Y axes, the team’s ‘cryo-bioprinting’ process sees them frozen and stacked vertically, in a way that allows for the creation of freestanding, mixed-cell tissues. According to the scientists, their technique also yields tissues that are more robust and versatile than those produced via conventional bioprinting, particularly when it comes to those anisotropic in nature, thus they say it could now find regenerative medicine, drug discovery, or personalized therapeutic applications.

To overcome the tissue-stacking issues, the researchers have turned to ‘ice-templating,’ a freezing process that causes microchannels to form within cell-laden hydrogel-based structures once they thaw. Naturally, doing so would ordinarily damage the viability of such cells, so to prevent this, the team loaded theirs with the cryoprotective agents (CPAs) melezitose and dimethyl sulfoxide.

Once frozen, the researchers then used ultraviolet (UV) light to vertically cross-link this novel bio-ink, and extrude it into tissues composed of high-resolution, honeycomb-like microchannel networks, capable of supporting various different types of cell, whether they be skeletal muscle myoblasts or human umbilical vein endothelial cells.

Our results indicate that [our] bio-ink, consisting of gelatin methacryloyl and CPAs, could be effectively used in vertical 3D cryo-bioprinting to enable cell encapsulation at high viability,” explained the team in their paper. “With the help of the interconnected, anisotropic, gradient microchannels formed by directional freezing during the process, the desired cellular alignments were also realized.

Given that 3D bioprinting is an emerging technology, it’s hardly surprising that its format is continually subject to change, with researchers constantly bringing innovative new ideas to the field. Just last month, scientists at the UK’s University of Birmingham and University of Huddersfield, revealed that they had developed a novel skin 3D bioprinting technique that enables the treatment of chronic wounds.

Elsewhere, on a more commercial level, Inventia Life Science raised $25 million towards the development of its RASTRUM 3D bioprinting technology in December 2021. In effect, the firm’s approach is designed to enable the layering of cell-loaded droplets onto one another at pace, in a way that allows them to join on contact and doesn’t affect their overall viability.

Looking even further back, researchers at Imperial College London have also experimented with cell-freezing as a means of bioprinting viable human implants.

Source: https://3dprintingindustry.com/

How to Regrow Amputated Limbs

Scientists in the US have successfully regrown the lost legs of a group of frogs in a significant advance for regenerative medicine. The research is an important step to one day helping people who have experienced the loss of a limb and opens the door to the potential use of a similar treatment on humans in the future.

The African clawed frog used in the research does not have the ability to naturally regenerate a limb and was treated with a five-drug cocktail over 24 hours. That brief treatment set in motion an 18-month period of regrowth that restored a functional leg.

It’s exciting to see that the drugs we selected were helping to create an almost complete limb,” said Nirosha Murugan, research affiliate at the Allen Discovery Centre at Tufts and first author of the paper outlining the experiment. “The fact that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action”.

The researchers used a group of 115 adult African clawed frogs. They amputated a limb of each frog, then split them up into three groups; one group received the full treatment, one group received no treatment to act as a control and one group received partial treatment. Scientists triggered the regenerative process in the frogs by enclosing the wound for 24 hours in a silicone cap, which they call a BioDome, containing a silk protein gel loaded with the five-drug cocktail. The drugs each had a different purpose, including tamping down inflammation and encouraging the new growth of nerve fibres, blood vessels, and muscle. The bioreactor helped to stop the natural tendency to close off the stump, and instead encourage the regenerative process.

Source: https://www.euronews.com/

Reprogramming Blood Cells To Fight Against COVID-19

Scientists report that they have successfully created airway basal stem cells in vitro from induced pluripotent stem cells by reprogramming blood cells taken from patients. Given that airway basal cells are defined as stem cells of the airways because they can regenerate the airway epithelium in response to injury, this study may help accelerate research on diseases impacting the airway, including COVID-19, influenza, asthma, and cystic fibrosis, according to the team led by researchers at the Center for Regenerative Medicine at Boston Medical Center and Boston University (CReM), in collaboration with the University of Texas Health Science Center at Houston (UTHealth).

These findings represent a critical first step towards airway regeneration, which will advance the field of regenerative medicine as it relates to airway and lung diseases, added the scientists.

The study, “Derivation of Airway Basal Stem Cells from Human Pluripotent Stem Cells,” published in Cell Stem Cell, outlines how to generate and purify large quantities of airway basal stem cells using patient samples. This allows for the development of individual, disease-specific airway basal stem cells in a lab that can be used to develop disease models, which may ultimately lead to drug development and a platform in which targeted drug approaches can be tested.

The study’s findings and cells will be shared freely given the CReM’s “Open Source Biology” philosophy, or sharing of information and findings that will help advance science across the globe.

Human lungs, computer illustration.

Human Airway Basal Stem Cells

The derivation of tissue-specific stem cells from human induced pluripotent stem cells (iPSCs) would have broad reaching implications for regenerative medicine. Here, we report the directed differentiation of human iPSCs into airway basal cells (iBCs), a population resembling the stem cell of the airway epithelium,” the investigators wrote.

Simply put, we have developed a way to reproduce patient-specific airway basal cells in the lab, with the ultimate goal of being able to regenerate the airway for patients with airway diseases,” said Finn Hawkins, MB, a pulmonologist and physician-scientist at Boston Medical Center, principal investigator in the CReM and the Pulmonary Center, and the study’s first author.

These results could lead to a better understanding, and therefore treatments for, a variety of airway diseases,” noted Shingo Suzuki, PhD, co-first author and post-doctoral researcher at UTHealth. For example, cystic fibrosis is caused by a genetic mutation that is present in all of the airway cells. “If we could make pluripotent stem cells using a sample from a patient who has cystic fibrosis, correct the mutation and replace the defective airway cells with corrected airway basal cells that are otherwise genetically identical, we might eventually be able to cure the disease, and other diseases in the future using this same technology,” added Hawkins.

Source: https://www.genengnews.com/