Urine and Regenerative Dentistry

In the quest for regenerative medicine, a Chinese research team has found a novel way of growing human teeth, from stem cells taken from urine.

Scientists around the world continue to investigate ways to regenerate teeth lost to aging and poor dental hygiene, hoping to soon find a technique to make the possible the plasticity of the human body — as Michelangelo sculpted David.

Stem cells from urine were used by researchers at the Guangzhou Institutes of Biomedicine and Health to grow a clump of cells forming a rudimentary tooth.

“The tooth-like structure contained dental pulp, dentin, enamel space and enamel organ,” the researchers wrote in Cell Regeneration Journal. “In particular, these regenerative teeth contain enamel with ameloblast-like cells of human origin and possess physical properties found in the regular human tooth.

“Thus, human [stem cells] could be a candidate source of seed cells on human tooth tissue-engineering for further drug screening or regenerative therapies.”

The findings demonstrated that stem cells from urine could potentially be used as a source of pluripotent stem cells, useful for developing many different parts of the human body. In 2011 research published the Journal of the American Society of Nephrology, a team from the South China Institute for Stem Cell Biology and Regenerative Medicine demonstrated a noninvasive method for generating induced pluripotent stem cells (iPSC) from urine.

The Chinese investigators found urine to be a potential wellspring for regenerative medicine. “There is no consensus regarding the preferred tissue from which to harvest donor cells for reprogramming into iPSCs, and some donor cell types may be more prone than others to accumulation of epigenetic imprints and somatic cell mutations,” the researchers wrote, describing their use of renal tubular cells from urine.

“This procedure eliminates many problems associated with other protocols, and the resulting [stem cells] display an excellent ability to differentiate,” they concluded. “These data suggest that urine may be a preferred source for generating” such cells.

However, others say urine is a poor choice from which to derive stem cells for regenerative medicine. “It is probably one of the worst sources, there are very few cells in the first place and the efficiency of turning them into stem cells is very low,” Chris Mason, a researcher at University College, London, told reporters. “You just wouldn’t do it in this way.”

Stem cells from urine presented a much higher risk of contamination through bacteria than with other sources, Mason said. “The big challenge here is the teeth have got a pulp with nerve and blood vessels which have to make sure they integrate to get permanent teeth.”

Still, the Chinese researchers said they had intended the study as only a preliminary step for further study “toward the final dream of total regeneration of human teeth for clinical therapy”.

The findings demonstrated the ability to use such stem cells to regenerate “patient-specific” dental tissues, or even teeth, as regenerative therapy.

 

Source: Cai J, Zhang Y, Liu P, Chen S, Wu X, Sun Y. Generation of tooth-like structures from integration-free human urine inducedpluripotent stem cells. Cell Regeneration. 2013.

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Journal ListCell Regen (Lond)v.2(1); 2013PMC4230506

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Cell Regen (Lond). 2013; 2(1): 6.

Published online 2013 Jul 30. doi:  10.1186/2045-9769-2-6

PMCID: PMC4230506

PMID: 25408878

Generation of tooth-like structures from integration-free human urine induced pluripotent stem cells

Jinglei Cai, Yanmei Zhang, Pengfei Liu, Shubin Chen, Xuan Wu, Yuhua Sun, Ang Li, Ke Huang, Rongping Luo, Lihui Wang, Ying Liu, Ting Zhou, Shicheng Wei, Guangjin Pan, and Duanqing PeipastedGraphic_1.png

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This article has been cited by other articles in PMC.

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Abstract

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Background

Tooth is vital not only for a good smile, but also good health. Yet, we lose tooth regularly due to accidents or diseases. An ideal solution to this problem is to regenerate tooth with patients’ own cells. Here we describe the generation of tooth-like structures from integration-free human urine induced pluripotent stem cells (ifhU-iPSCs).

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Results

We first differentiated ifhU-iPSCs to epithelial sheets, which were then recombined with E14.5 mouse dental mesenchymes. Tooth-like structures were recovered from these recombinants in 3 weeks with success rate up to 30% for 8 different iPSC lines, comparable to H1 hESC. We further detected that ifhU-iPSC derived epithelial sheets differentiated into enamel-secreting ameloblasts in the tooth-like structures, possessing physical properties such as elastic modulus and hardness found in the regular human tooth.

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Conclusion

Our results demonstrate that ifhU-iPSCs can be used to regenerate patient specific dental tissues or even tooth for further drug screening or regenerative therapies.

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Electronic supplementary material

The online version of this article (doi:10.1186/2045-9769-2-6) contains supplementary material, which is available to authorized users.

Keywords: Human urine, Integration-free iPSCs, Recombinant tooth, Bioengineered tooth, Dental epithelium

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Background

The goal of regenerative medicine is to regenerate fully functional tissues or organs that can replace lost or damaged ones occurred during diseases, injury and aging [1, 2]. The advent of iPSCs should speed up the application of regenerative tissues or organs such as tooth in the clinic [3]. While iPSC-derived cells have been tested in animal models [4–7], no solid organs or tissues such as tooth have been generated with human iPSCs. The tooth represents one of the best experimental models in organogenesis [8, 9], and is easily accessible for human replacement therapy [10]. Tooth is formed by reciprocal interactions between epithelium and mesenchymal cells derived from the cranial neural crest [11, 12]. Developmentally, the odontogenic potential shifts from the dental epithelium to dental mesenchyme at bud stage (Embryonic day 12, E12) [13, 14]. Then, the epithelium differentiates into ameloblasts and finally forms the enamel, while the mesenchyme differentiates into the dentin, cementum and dental pulp [15]. Tooth stem cells such as dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and gum stem cells (GSCs) have been isolated and investigated for tooth regeneration [16–18]. Recently, Arakaki and colleagues reported that mouse iPSCs (miPSCs) could be differentiated into ameloblasts via interactions with dental epithelium and these miPSCs derived epithelial cells were positive with the epithelial cell markers p63, cytokeratin-14 (K14), and ameloblast markers ameloblastin and enamelin [19]. Shortly after, another group differentiated miPSCs into neural crest-like cells to generate odontoblasts that express dental mesenchyme markers Msx1, Pax9, Lhx6, and odontoblast marker dentin sialoprotein (DSP) [20]. Recently, miPSCs were mixed

 

 

 

 

Growing Teeth and Four More Odd Uses for Urine

For those who’ve lost their teeth to accidents and decay, there may be a new way to restore your pearly whites: urine.

Scientists in China have successfully used cells found in human urine to regrow teeth. If that’s not enough of an ick factor, the scientists grew the teeth in mouse kidneys.

urine clock picture
Hirenbhai Bheda displays a wall clock that runs on cow urine in Luni, India, on June 5. Photograph by Sam Panthaky/AFP/Getty Images

The researchers, led by Duanqing Pei at the Chinese Academy of Sciences in Guangzhou, converted cells collected from urine into what’s called pluripotent stem cells, which can become any kind of cell in the body. These stem cells were then mixed with dental tissue from mouse embryos and implanted into mouse kidneys. (Read more about stem cells.)

The entire process took just a few weeks: several days to incubate the stem cells, and then three weeks to grow them in the kidneys, according to the study, published July 30 in the journal Cell Regeneration.

These were not, however, normal teeth. They were probably even less useful than George Washington’s mythical wooden dentures, given that the teeth were soft and misshapen and not actually, you know, attached to a person’s jaw.

In an interview with the BBC, University College London stem cell biologist Chris Mason said urine “is probably one of the worst sources [for teeth]—there are very few cells in the first place and the efficiency of turning them into stem cells is very low.” (Explore a human-body interactive.)

And for the teeth to work, they’d have to be integrated into the gum’s “pulp” of nerves and blood vessels, which would be a “big challenge,” Mason said.

Though human urine hasn’t yet unemployed the tooth fairy, other researchers have come up with some surprising and creative ways to reuse the liters of liquid gold each of us create every day.

Urine as Fuel

At the 2012 Maker Faire for innovators in Lagos, Nigeria, a group of three schoolgirls created a backup generator that could run on human urine. The device uses an electrolytic cell to break down the molecules found in urine and extract pure hydrogen. (Also see “Urine Battery Turns Pee Into Power.”)

The hydrogen is passed through a cylinder of borax to remove any moisture, and then delivered to the generator. The girls used one-way valves to reduce any explosion risks from the hydrogen. One liter of urine can produce up to six hours of electricity.

Other scientists from the Bristol Robotics Laboratory have also been investigating urine fuel cells, only they used microbes to break down the molecules in urine and produce the electricity.

Urine as Medication

Peeing into a cup generally yields a diagnosis, not a pharmaceutical. But when researchers analyzed the urine of menopausal women, they realized they could extract an important—and potentially lucrative—medication for infertility.

As a woman approaches menopause, her ovaries start to become deaf to the monthly siren calls of hormones. The pituitary gland responds by secreting even more hormones, such as follicle-stimulating hormone and luteinizing hormone, which stimulate eggs to mature in the ovary.

Levels of these hormones are often low in infertile women, which gave scientists the brilliant idea to gather urine from perimenopausal women to extract and purify the precious hormones. Thus was born the infertility drugs Menopur and Pergonal.

Urine as Compost

When researchers combined compost with human urine, they found they had created a fertilizer that is superior to compost alone. The trick appears to be the extra nitrogen from the urine, which helps to boost plants’ growth.

Although it isn’t as powerful as commercial fertilizers, urine is freely available and a potentially more cost-effective and environmentally friendly fertilizer. (Related: “Human Pee Added to Compost Boosts Crops.”)

Urine as Water

People have been drinking urine for millennia, often for health reasons. But NASA has developed a new filtration system to turn human wastewater like sweat and urine into potable drinking water. The Forward Osmosis Bag (FOB) was designed to give astronauts an extra source of drinking water in space. The FOB, however, can be used outside of zero gravity and, if the technology is scaled up, may help create additional drinking water around the globe.

These ideas are not, of course, the only ways urine can be used—people are inventing new things every day. Even my cat has gotten in on the game, creating inventive works of art on my rug after an inadvertent change of kitty litter brands.

What ideas do you have for using urine?