Video

How to Cure Aging – During Your Lifetime?

November 18, 2017

 

Advertisements

Japanese scientists have used skin cells to restore a patient’s vision for the first time

July 10, 2016

314152310_1024

Japanese scientists have reported the first successful skin-to-eye stem cell transplant in humans, where stem cells derived from a patient’s skin were transplanted into her eye to partially restore lost vision.

The patient, a 70-year-old woman diagnosed with age-related macular degeneration (AMD) – the leading cause of vision impairment in older people – received the experimental treatment back in 2014 as part of a pilot study. Now, closing in on two years after the transplant took place, the scientists are sharing the results.

The researchers took a small piece of skin from her arm (4 mm in diameter) and modified its cells, effectively reprogramming them into induced pluripotent stem cells (iPSC).

Pluripotent stem cells have the ability to differentiate into almost any type of tissue within the body, which is why skin cells taken from an arm can be repurposed into retinal tissue.

Once the cells were coaxed to develop into retinal pigment epithelium (RPE), they were cultured in the lab to grow into an ultra-thin sheet, which was then transplanted behind the retina of the patient.

“I am very pleased that there were no complications with the transplant surgery,” said project leader Masayo Takahashi from the Riken Centre for Developmental Biology in 2014. “However, this is only the first step for use of iPSC in regenerative medicine. I have renewed my resolve to continue forging ahead until this treatment becomes available to many patients.”

While it’s definitely still early days for this experimental procedure, the signs so far are promising.

The team held off on reporting their results until now to monitor the patient’s progress and gauge how successfully the modified cells lasted, but they’ve just reported that the transplanted cells survived without any adverse events for over a year, resulting in slightly improved vision for the patient.

“The transplanted RPE sheet survived well without any findings [or] indication of immune rejections nor adverse unexpected proliferation for one and a half years, achieving our primary purpose of this pilot study,” the team said in a statement this week.

“I am glad I received the treatment,” the patient told The Japan Times last year. “I feel my eyesight has brightened and widened.”

While it’s not a complete restoration of the patient’s vision, the study shows a significant step forward in the use of induced pluripotent stem cells – which scientists think might be used to treat a range of illnesses, such as Parkinson’s and Alzheimer’s disease, not just vision problems.

A number of other studies are also showing positive results in restoring sight with stem cell treatments. Earlier in the year, researchers in China and the US were able to improve the vision of babies with cataracts by manipulating protein levels in stem cells.

Even more remarkably, a woman in Baltimore who was blind for more than five years had some of her vision restored after stem cells were extracted from her bone marrow and injected into her eyes. While many questions remain about that particular treatment, there’s no denying that stem cell research is a hugely exciting field of study.

The findings were presented at the 2016 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle.

http://www.sciencealert.com/japanese-scientists-have-used-skin-cells-to-restore-a-patient-s-vision-for-the-first-time

Scientists Grow Full-Sized, Beating Human Hearts From Stem Cells

June 18, 2016

110957_web

Of the 4,000 Americans waiting for heart transplants, only 2,500 will receive new hearts in the next year. Even for those lucky enough to get a transplant, the biggest risk is the their bodies will reject the new heart and launch a massive immune reaction against the foreign cells. To combat the problems of organ shortage and decrease the chance that a patient’s body will reject it, researchers have been working to create synthetic organs from patients’ own cells. Now a team of scientists from Massachusetts General Hospital and Harvard Medical School has gotten one step closer, using adult skin cells to regenerate functional human heart tissue, according to a study published recently in the journal Circulation Research.

Ideally, scientists would be able to grow working hearts from patients’ own tissues, but they’re not quite there yet. That’s because organs have a particular architecture. It’s easier to grow them in the lab if they have a scaffolding on which the cells can build, like building a house with the frame already constructed.

In their previous work, the scientists created a technique in which they use a detergent solution to strip a donor organ of cells that might set off an immune response in the recipient. They did that in mouse hearts, but for this study, the researchers used it on human hearts. They stripped away many of the cells on 73 donor hearts that were deemed unfit for transplantation. Then the researchers took adult skin cells and used a new technique with messenger RNA to turn them into pluripotent stem cells, the cells that can become specialized to any type of cell in the human body, and then induced them to become two different types of cardiac cells.

After making sure the remaining matrix would provide a strong foundation for new cells, the researchers put the induced cells into them. For two weeks they infused the hearts with a nutrient solution and allowed them to grow under similar forces to those a heart would be subject to inside the human body. After those two weeks, the hearts contained well-structured tissue that looked similar to immature hearts; when the researchers gave the hearts a shock of electricity, they started beating.

While this isn’t the first time heart tissue has been grown in the lab, it’s the closest researchers have come to their end goal: Growing an entire working human heart. But the researchers admit that they’re not quite ready to do that. They are next planning to improve their yield of pluripotent stem cells (a whole heart would take tens of billions, one researcher said in a press release), find a way to help the cells mature more quickly, and perfecting the body-like conditions in which the heart develops. In the end, the researchers hope that they can create individualized hearts for their patients so that transplant rejection will no longer be a likely side effect.

http://www.popsci.com/scientists-grow-transplantable-hearts-with-stem-cells

Researchers coax human stem cells to form complex tissues

January 23, 2016

researchersc

A new technique for programming human stem cells to produce different types of tissue on demand may ultimately allow personalized organs to be grown for transplant patients.

The technique, which also has near-term implications for growing organ-like tissues on a chip, was developed by researchers at MIT and is unveiled in a study published today in the journal Nature Communications.

Growing organs on demand, using derived from patients themselves, could eliminate the lengthy wait that people in need of a transplant are often forced to endure before one becomes available.

It could also reduce the risk of a patient’s immune system rejecting the transplant, since the tissue would be grown from the patient’s own cells, according to Ron Weiss, professor of biological engineering at MIT, who led the research.

“Imagine that there is a patient with liver complications,” Weiss says. “We could take skin cells from that person and then [convert] them into stem cells, and then genetically program them to make the liver tissue, and transplant that into the patient.”

A rudimentary organ

The researchers developed the new technique while investigating whether they could use stem cells to produce pancreatic beta cells for treating patients with diabetes.

In order to do this, the researchers needed to devise a means to convert stem cells into on demand.

As a first step in this process, they took human induced pluripotent stem (IPS) cells—stem cells generated from adult fibroblast, or —and converted them into “endoderm,” one of the three primary cell types in a developing organism. Endoderm, mesoderm, and ectoderm make up the three so-called germ layers that contribute to nearly all of the different cell types in the body. “They are the first real step of [cell] differentiation,” Weiss says.

The researchers developed a method to use a type of small molecule called dox to induce the IPS cells to express a protein known as GATA6. This protein can convert IPS cells into endoderm.

Rather than immediately attempting to convert these endoderm cells into though, the paper’s lead author, Patrick Guye, a former postdoc in Weiss’ lab and currently laboratory head with Sanofi-Aventis in Frankfurt, Germany, then decided to allow the cells to continue growing, to monitor their progress.

After two weeks, the researchers found that the endoderm, and some mesoderm also present in the cell culture, had matured further, to form a liver “bud,” or small, rudimentary liver.

“We observed the development of many cells types found in the fetal liver, including the development of blood vessel-like networks, various mesenchymal precursors, and the formation of early red and within our liver-like tissue,” Guye says. “This is especially exciting, as the process looks very similar if not identical to what is happening in the early liver bud in vivo, that is, in our own development.”

What’s more, the researchers discovered that only those IPS cells that had been exposed to more of the genetic programming, and had therefore gone on to produce more GATA6, became . Alongside these were IPS cells that did not make much GATA6, which went on to form ectoderm instead, and then further matured to become early telencephalon, or forebrain.

By controlling how much GATA6 the cells expressed, the researchers were able to determine how much liver bud and how much forebrain tissue was generated, Weiss says.

This suggests that the technique could be used to produce not just individual tissue types, but different combinations of tissue, he says.

“The fact that we are able to produce endoderm, mesoderm, and ectoderm gives us great hope that we can take each of these germ layers and hopefully grow any kind of tissue we want,” he says.

Liver-on-a-chip

While it is likely to be some time before the technique can be used to generate transplant organs, it could be used almost immediately to grow different human tissue on which to test new drugs, Weiss says.

Using human stem cell-derived organ tissue to test new treatments could be far more reliable than testing on animals, since different species may react differently to a drug, he says.

The technique could also allow clinicians to carry out patient-specific drug testing. “If you are not sure whether you will have complications from taking a particular drug, then before you take it you could try it out on your own liver-on-a-chip,” Weiss says.

Similarly, the organ-on-a-chip could be used to monitor the interaction between different drugs that people may be taking.

“As people age, some are taking 10, 15, or 20 drugs together, and it’s impossible for the pharmaceutical companies to test all of these combinations for every individual. But we would be able to test that out,” he says. “That is something that can be done now.”

In addition to these therapeutic applications, the technique could allow researchers to gain a better understanding of the development of different types of tissue, such as the liver and neurons.

The paper reveals some intrinsic mechanisms underlying the interactions of stem cells during liver development, and provides a useful model that sheds light on the complex process of embryogenesis, says Bing Song, a professor of engineering at Cardiff University in the UK, who was not involved in the research.

“In my field, which is combining genetically modified stem cells and physical stimulation (electrical and magnetic) to cure spinal cord injuries and degenerative disease, the paper has given me some very useful ideas,” he says.

The researchers now hope to investigate whether they can use the technique to grow other organs on demand, such as a pancreas.

http://medicalxpress.com/news/2016-01-coax-human-stem-cells-complex.html

Fountain of youth uncovered in mammary glands of mice, by breast cancer researchers

April 13, 2015

a1b72946d6277cc3accf46b31b7cd3b0

The Fountain of Youth has been discovered and it’s not in Florida as Ponce de Leon claimed. Instead, it was found in the mammary glands of genetically modified mice.

A research team led by Professor Rama Khokha has found that when two factors that control tissue development are removed, you can avoid the impact of aging.

Think of tissue as a building that is constantly under renovation. The contractors would be “metalloproteinases,” which are constantly working to demolish and reconstruct the tissue. The architects in this case, who are trying to reign in and direct the contractors, are known as “tissue inhibitors of metalloproteinases” — or TIMPs. When the architect and the contractors don’t communicate well, a building can fall down. In the case of tissue, the result can be cancer.

To understand how metalloproteinases and TIMPs interact, medical researchers breed mice that have one or more of the four different types of TIMPs removed. Khokha’s team examined the different combinations and found that when TIMP1 and TIMP3 were removed, breast tissue remained youthful in aged mice. The results are presented in Nature Cell Biology.

In the normal course of aging, your tissue losses its ability to develop and repair as fast as it did when you were young. That’s because stem cells, which are abundant in your youth, decline with the passing of time. The U of T team found that with the TIMP1 and TIMP3 architects missing, the pool of stem cells expanded and remained functional throughout the lifetime of these mice.

“Normally you would see these pools of stem cells, which reach their peak at six months in the mice, start to decline. As a result, the mammary glands start to degenerate, which increases the risk of breast cancer occurring,” explains Khokha. “However, we found that in these particular mice, the stem cells remained consistently high when we measured them at every stage of life.”

The team also found that despite large number of stem cells, there was no increased risk of cancer.

“It’s generally assumed that the presence of a large number of stem cells can lead to an increased cancer risk,” says Khokha. “However, we found these mice had no greater predisposition to cancer.”

The next step in this research is to understand why this is happening. Khokha is also working with her colleagues at Princess Margaret to see how altered tissue remodeling might prevent cancer development or lead to a new therapeutic treatment for patients.

Khokha is a Professor in the departments of Medical Biophysics and Laboratory Medicine and Pathobiology, as well as a Senior Scientist at the Princess Margaret Cancer Centre. Her work is supported by the Canadian Breast Cancer Foundation and the Canadian Cancer Society Research Institute.

She was drawn to this research by the complexity of breast tissue.

“It’s a fundamental tissue that is constantly reorganizing. It develops at puberty. It goes through cycles of change in the adult female. New structures appear and regress,” she explains. “It is therefore a good system to explore in order to understand tissue maintenance and epithelial cell turnover — the cells that underlie carcinomas, the most frequent type of cancer.”

She worked closely with the paper’s lead author, Dr. Hartland Jackson, who earned his PhD under her supervision. He is now completing a post-doctoral fellowship at the University of Zurich’s Institute of Molecular Life Sciences.

“He’s continuing his work in breast cancer and learning some really interesting techniques that, I hope, he’ll bring back here,” says Khokha, who beams with pride at her former student’s success.


Story Source:

The above story is based on materials provided by University of Toronto. The original article was written by Liam Mitchell. Note: Materials may be edited for content and length.


Journal Reference:

  1. Hartland W. Jackson, Paul Waterhouse, Ankit Sinha, Thomas Kislinger, Hal K. Berman, Rama Khokha. Expansion of stem cells counteracts age-related mammary regression in compound Timp1/Timp3 null mice. Nature Cell Biology, 2015; 17 (3): 217 DOI: 10.1038/ncb3118

Japanese woman is first recipient of next-generation stem cells

September 14, 2014

Stem_cells_240384c

“We’ve taken a momentous first step toward regenerative medicine using iPS cells,” Takahashi said in a statement. “With this as a starting point, I definitely want to bring [iPS cell-based regenerative medicine] to as many people as possible.”

A Japanese woman in her 70s is the world’s first recipient of cells derived from induced pluripotent stem cells, a technology that has created great expectations since it could offer the same advantages as embryo-derived cells but without some of the controversial aspects and safety concerns.

In a two-hour procedure starting at 14:20 local time today, a team of three eye specialists lead by Yasuo Kurimoto of the Kobe City Medical Center General Hospital, transplanted a 1.3 by 3.0 millimetre sheet of retinal pigment epithelium cells into an eye of the Hyogo prefecture resident, who suffers from age-related macular degeneration.

The procedure took place at the Institute of Biomedical Research and Innovation Hospital, next to the RIKEN Center for Developmental Biology (CDB) where ophthalmologist Masayo Takahashi had developed and tested the epithelium sheets. She derived them from the patient’s skin cells, after producing induced pluripotent stem (iPS) cells and then getting them to differentiate into retinal cells.

Afterwards, the patient experienced no effusive bleeding or other serious problems, RIKEN has reported.

The patient “took on all the risk that go with the treatment as well as the surgery”, Kurimoto said in a statement released by RIKEN. “I have deep respect for bravery she showed in resolving to go through with it.”

He hit a somber note in thanking Yoshiki Sasai, a CDB researcher who recenty committed suicide. “This project could not have existed without the late Yoshiki Sasai’s research, which led the way to differentiating retinal tissue from stem cells.”

Kurimoto also thanked Shinya Yamanaka, a stem-cell scientist at Kyoto University “without whose discovery of iPS cells, this clinical research would not be possible.” Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for that work.

Kurimoto performed the procedure a mere four days after a health-ministry committee gave Takahashi clearance for the human trials (see ‘Next-generation stem cells cleared for human trial‘).

To earn that, Takahashi and her collaborators had done safety studies in both monkeys and mice. The animal tests found that iPS cells were not rejected and did not lead to the growth of tumours (see ‘Stem cells cruise to clinic‘).

Age-related macular degeneration results from the breakdown of retinal epithelium, a layer of cells that support photoreceptors needed for vision. The procedure Kurimoto performed is unlikely to restore his patient’s vision. However, researchers around the world will be watching closely to see whether the cells are able to check the further destruction of the retina while avoiding potential side-effects, such as bringing about an immune reaction or inducing cancerous growth.

“We’ve taken a momentous first step toward regenerative medicine using iPS cells,” Takahashi said in a statement. “With this as a starting point, I definitely want to bring [iPS cell-based regenerative medicine] to as many people as possible.”

http://www.nature.com/news/japanese-woman-is-first-recipient-of-next-generation-stem-cells-1.15915

Light coaxes stem cells to repair teeth: Noninvasive laser therapy could radically shift dental treatment

May 29, 2014

images

Scientists have used low-power light to trigger stem cells inside the body to regenerate tissue. The research lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more

A Harvard-led team is the first to demonstrate the ability to use low-power light to trigger stem cells inside the body to regenerate tissue, an advance they reported in Science Translational Medicine. The research, led by Wyss Institute Core Faculty member David Mooney, Ph.D., lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more.

The team used a low-power laser to trigger human dental stem cells to form dentin, the hard tissue that is similar to bone and makes up the bulk of teeth. What’s more, they outlined the precise molecular mechanism involved, and demonstrated its prowess using multiple laboratory and animal models.

A number of biologically active molecules, such as regulatory proteins called growth factors, can trigger stem cells to differentiate into different cell types. Current regeneration efforts require scientists to isolate stem cells from the body, manipulate them in a laboratory, and return them to the body — efforts that face a host of regulatory and technical hurdles to their clinical translation. But Mooney’s approach is different and, he hopes, easier to get into the hands of practicing clinicians.

“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,” said Mooney, who is also the Robert P. Pinkas Family Professor of Bioengineering at Harvard’s School of Engineering and Applied Sciences (SEAS). “It would be a substantial advance in the field if we can regenerate teeth rather than replace them.”

The team first turned to lead author and dentist Praveen Arany, D.D.S., Ph.D., who is now an Assistant Clinical Investigator at the National Institutes of Health (NIH). At the time of the research, he was a Harvard graduate student and then postdoctoral fellow affiliated with SEAS and the Wyss Institute.

Arany took rodents to the laboratory version of a dentist’s office to drill holes in their molars, treat the tooth pulp that contains adult dental stem cells with low-dose laser treatments, applied temporary caps, and kept the animals comfortable and healthy. After about 12 weeks, high-resolution x-ray imaging and microscopy confirmed that the laser treatments triggered the enhanced dentin formation.

“It was definitely my first time doing rodent dentistry,” said Arany, who faced several technical challenges in performing oral surgery on such a small scale. The dentin was strikingly similar in composition to normal dentin, but did have slightly different morphological organization. Moreover, the typical reparative dentin bridge seen in human teeth was not as readily apparent in the minute rodent teeth, owing to the technical challenges with the procedure.

“This is one of those rare cases where it would be easier to do this work on a human,” Mooney said.

Next the team performed a series of culture-based experiments to unveil the precise molecular mechanism responsible for the regenerative effects of the laser treatment. It turns out that a ubiquitous regulatory cell protein called transforming growth factor beta-1 (TGF-β1) played a pivotal role in triggering the dental stem cells to grow into dentin. TGF-β1 exists in latent form until activated by any number of molecules.

Here is the chemical domino effect the team confirmed: In a dose-dependent manner, the laser first induced reactive oxygen species (ROS), which are chemically active molecules containing oxygen that play an important role in cellular function. The ROS activated the latent TGF-β1complex which, in turn, differentiated the stem cells into dentin.

Nailing down the mechanism was key because it places on firm scientific footing the decades-old pile of anecdotes about low-level light therapy (LLLT), also known as Photobiomodulation (PBM).

Since the dawn of medical laser use in the late 1960s, doctors have been accumulating anecdotal evidence that low-level light therapy can stimulate all kind of biological processes including rejuvenating skin and stimulating hair growth, among others. But interestingly enough, the same laser can be also be used to ablate skin and remove hair — depending on the way the clinician uses the laser. The clinical effects of low-power lasers have been subtle and largely inconsistent. The new work marks the first time that scientists have gotten to the nub of how low-level laser treatments work on a molecular level, and lays the foundation for controlled treatment protocols.

“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, M.D., Ph.D., “and Dave and his team have added an innovative, noninvasive and remarkably simple but powerful tool to the toolbox.”

Next Arany aims to take this work to human clinical trials. He is currently working with his colleagues at the National Institute of Dental and Craniofacial Research (NIDCR), which is one of the National Institutes of Health (NIH), to outline the requisite safety and efficacy parameters. “We are also excited about expanding these observations to other regenerative applications with other types of stem cells,” he said.


Journal Reference:

  1. P. R. Arany, A. Cho, T. D. Hunt, G. Sidhu, K. Shin, E. Hahm, G. X. Huang, J. Weaver, A. C.-H. Chen, B. L. Padwa, M. R. Hamblin, M. H. Barcellos-Hoff, A. B. Kulkarni, D. J. Mooney. Photoactivation of Endogenous Latent Transforming Growth Factor- 1 Directs Dental Stem Cell Differentiation for Regeneration. Science Translational Medicine, 2014; 6 (238): 238ra69 DOI: 10.1126/scitranslmed.3008234

http://www.sciencedaily.com/releases/2014/05/140528150559.htm