Shining a Light on Stem Cell Tooth Repair
A team from the Wyss Institute at Harvard University (MA, USA) has demonstrated how the use of low-power light can induce stem cells to regenerate certain tissues. The team’s findings were published recently in Science Translational Medicine.
The team triggered human dental stem cells using a low-power laser to form dentin, a hard tissue and forms the bulk of teeth. This method is far simpler than the complex manipulation of growth factor induction.
David Mooney, Robert P Pinkas Family Professor of Bioengineering at Harvard’s School of Engineering and Applied Sciences (SEAS) and a member of the Wyss Institute Core Faculty, explained: “Our treatment modality does not introduce anything new to the body, and lasers are routinely used in medicine and dentistry, so the barriers to clinical translation are low.” Mooney continued, “It would be a substantial advance in the field if we can regenerate teeth rather than replace them.”
To investigate the efficiency of the lasers, holes were drilled in the molars of rodents and then the dental pulp was treated with low-dose lasers. After 12 weeks, x-rays and microscopy confirmed the lasers had triggered dentin formation. The lasers induce the reactive oxygen species which in turn activate the TGF-β1 complex, causing the dental pulp stem cells to differentiate into dentin.
“The scientific community is actively exploring a host of approaches to using stem cells for tissue regeneration efforts,” said Wyss Institute Founding Director Don Ingber, “and Dave (Mooney) and his team have added an innovative, noninvasive and remarkably simple but powerful tool to the toolbox.”
Praveen Arany, an Assistant Clinical Investigator at the NIH, concluded: “We are also excited about expanding these observations to other regenerative applications with other types of stem cells.”
Sources: Arany PR, Cho A, Hunt TD et al. Photoactivation of endogenous latent transforming growth factor-1 directs dental stem cell differentiation for regeneration. Sci. Transl. Med. 6(238), 238ra69 (2014)D; Wyss Institute press release:http://wyss.harvard.edu/viewpressrelease/155/researchers-use-light-to-coax-stem-cells-to-repair-teeth
Light-Sensitive Retina Tissue Developed from Human-Induced Pluripotent Stem Cells
An article in a recent issue of Nature Communications has reported the development of 3D retinal tissue from human induced pluripotent stem (iPS) cells. The investigation, carried out by researchers at John Hopkins University School of Medicine (MD, USA), demonstrated that this retina tissue contained functioning photoreceptor cells that were capable of responding to light.
M Valeria Canto-Soler, study leader and an assistant professor of ophthalmology at the Johns Hopkins University School of Medicine, explained that “We have basically created a miniature human retina in a dish that not only has the architectural organization of the retina but also has the ability to sense light.”
The group differentiated human iPS cells in the hope of being able to grow replacement retinas using a blind patients own cells. “We knew that a 3D cellular structure was necessary if we wanted to reproduce functional characteristics of the retina,” says Canto-Soler, “but when we began this work, we didn’t think stem cells would be able to build up a retina almost on their own. In our system, somehow the cells knew what to do.”
Canto-Soler explained that the newly developed system gives them the ability to generate hundreds of mini-retinas at a time directly from a person affected by a particular retinal disease such as retinitis pigmentosa. This provides a unique biological system to study the cause of retinal diseases directly in human tissue, instead of relying on animal models.
Being able to grow photoreceptors that respond to light is the first step in the process of converting it into a visual image. However, Canto-Soler was cautious about the overall outcome of their study, saying “Is our lab retina capable of producing a visual signal that the brain can interpret into an image? Probably not, but this is a good start.”
Canto-Soler concluded that their findings “advance opportunities for vision-saving research and may ultimately lead to technologies that restore vision in people with retinal diseases.”
Sources: Zhong X, Gutierrez C, Xue T et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat. Commun. doi:10.1038/ncomms5047 (2014) (Epub ahead of print); John Hopkins University press release:www.hopkinsmedicine.org/news/media/releases/researchers_use_human_stem_cells_to_create_light_sensitive_retina_in_a_dish
The Next Stage of Tissue Regeneration
A group from the University of Nottingham (UoN) and its Malaysia Campus has developed a new class of injectable material that stimulates stem cells to form new blood vessels, heart and bone tissue, as well as regenerating damaging tissue. The team’s research is part of the ‘Rational Bioactive Materials Design for Tissue Generation’, an EU€11 million EU-funded initiative involving 21 research teams from across Europe, which hopes to produce new radical treatments that reduce the need for invasive surgery, optimize recovery and reduce the risk of undesirable scar tissue.
Kevin Shakesheff, Head of the School of Pharmacy at the UoN’s UK campus, explained: “This research heralds a step-change in approaches to tissue regeneration. Current biomaterials are poorly suited to the needs of tissue engineering and regenerative medicine,” Shakesheff continued. “Our aim is to develop new materials and medicines that will stimulate tissue regeneration rather than wait for the body to start the process itself.”
“Here in Malaysia we are looking at synthesizing microparticles that can be injected directly into a patient at the site of injury to promote tissue regrowth,” said Andrew Morris, an expert in transdermal drug delivery and Head of the School of Pharmacy at the UoN’s Malaysia Campus. “These microparticles would act as a scaffold to encourage regrowth in bone tissue, skeletal muscle and potentially even cardiac muscle.”
This research is going to have a significant impact on patients,” concluded Nashiru Billa, Associate Dean for Research in the Faculty of Science at the UoN’s Malaysia Campus. “In future, you could include anticancer drugs in the delivery system that would not only lead to the growth of the tissue but would also help kill cancer cells within the bone tissue.”
Source: University of Nottingham Malaysia campus: www.researchsea.com/html/article.php/aid/8233/cid/1/research/science/the_university_of_nottingham_malaysia_campus/taking_tissue_regeneration_beyond_state-of-the-art.html
Regenerated Human Corneas Restore Vision
Researchers in Boston (MA, USA) have used ABCB5, a molecule that is needed for corneal development and repair, to regrow human corneal tissue. The molecule acts as a marker for limbal stem cells (LSCs), which are crucial for healthy eye sight. The research was conducted by a collaboration between the Massachusetts Eye and Ear Infirmary, Boston Children’s Hospital, Brigham and Women’s Hospital and the VA Boston Healthcare System. The group believes their work will give hope to people with impaired or lost vision caused by burns, chemical injuries or eye diseases that damage the cornea. The research, recently been published in Nature, is one of the first known examples of constructing a tissue grown from an adult-derived human stem cell.
LSC deficiency is a major cause of blindness worldwide and transplantation is often the only therapeutic option. However, LSCs are difficult to identify, and therefore eye surgeons cannot be sure if the grafts are rich or poor in the essential stem cells. Bruce Ksander, Associate Professor of ophthalmology at Harvard Medical School (MA, USA), said: “LSCs are very rare, and successful transplants are dependent on these rare cells.” Ksander and his colleagues found that the gene ABCB5 is a key tracer molecule for LSCs and is also essential for maintaining the stem cells and growing and repairing the cornea. The lack of a functional ABCB5 gene in mice resulted in the loss of LSCS, and their corneas healed poorly after injury. “ABCB5 allows LSCs to survive, protecting them from apoptosis (programmed cell death),” said Markus Frank, a member of the Stem Cell Programme, Boston Children’s Hospital.
After receiving transplants of human ABCB5-positive LSCs, mice deficient in LSCs developed fully functioning restored corneas while control mice that received either no LSCs, or received ABCB5-negative LSCs failed to restore their corneas. Natasha Frank, Interim Clinical Chief of Genetics and Associate Physician of Medicine at the Brigham and Women’s Hospital, explained: “The mouse model allowed us for the first time to understand the role of ABCB5 in normal development, and should be very important to the stem cell field in general.” Although ABCB5 has been known about for some time in other parts of the body, this is the first time it has been spotted on LSCs, helping to single out these elusive cells. “This finding will now make it much easier to restore the corneal surface,” concluded Ksander. “It’s a very good example of basic research moving quickly to a translational application.”
Sources: Ksander BR, Kolovou PE, Wilson BJ et al. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature doi:10.1038/nature13426 (2014) (Epub ahead of print); Massachusetts Eye and Ear Infirmary press release:www.masseyeandear.org/news/press_releases/recent/2014_Nature_Growing_Corneas
– All stories written by Carissa Drake