Dental Stem Cells Grow New Teeth

Scientists at the Columbia University’s Dental School have perfected a “cell-homing-based tooth regeneration” procedure that allows the use of autologous stem cells to grow teeth, including molars. In this blog-article, i will first examine the procedure (Section A) and then dig a little deeper in this technique’s modus operandi (Section B). Thereafter, i will discuss perspectives and clinical trials (Section C) and conclude with an over-all assessment.

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Section A

Human dental stem cells can be obtained from postnatal teeth, extracted wisdom teeth or exfoliated deciduous teeth. Due to their differentiation potential, these mesenchymal stem cells are promising for both teeth repair as well as the regeneration of other tissues. Therefore, the development of dental tissue regeneration represents a suitable but challenging, target for dental stem cell therapies.

How the Stem Cell Dental Procedure Works

Tooth regeneration is a stem cell based regenerative medicine procedure. It is tissue engineering via stem cell biology. Its purpose is to replace damaged or lost teeth by regrowing them from autologous stem cells. (1)

The dental bio-engineering is done via somatic stem cells that are collected and reprogrammed to induced pluripotent stem cells which can then be placed in the dental lamina directly or placed in a reabsorbable biopolymer  in the shape of the new tooth. (2)

Within 2 months, the stem cells grow into a new tooth, an exact match of the precedent tooth. As a bonus, the stem cells also produce the bone that connects the tooth to the jaw, eliminating the need for bone grafting, a procedure that can delay dental implant surgery 6 to 9 months. With regenerated teeth, there is also no risk of the implanted tooth falling out. (3)

While the dental company Odontics’ scientists have made significant advancements in stem cell tooth regeneration, the technique does not yet appear to be available in most dental clinics, let alone the official new standard of care. However, Dr. Jeremy Mao, the Edward V. Zegarelli Professor of Dental Medicine at Columbia University Medical Center, has recently made significant progress using a growth factor-covered, three-dimensional scaffold.

In this perspective, Dr. Mao has developed a way to guide stem cells to the scaffold, where a tooth then grows and attaches to the surrounding tissue in as little as 9 weeks. This was one of the last obstacles in this dental bioengineering scheme (4)

This technology, referred to as cell-homing-based tooth regeneration, alleviates the need to prepare stem cells in an external environment, such as a Petri dish. Columbia University is in the process of or already has patented this technology. (5)

Screen Shot 2016-01-25 at 1.09.27 PM
Human molar scaffolding from the lab of Dr. Jeremy Mao.
Credit: Image courtesy of Columbia University Medical Center

Section B

Mechanisms of Action: From Genes to stem Cell Differentiation

Young et al. first demonstrated in 2002 that teeth could be regenerated from cells. (6) Thereafter, scientists at the Dental Institute of King’s College London successfully used stem cells to grow new teeth in mice. A little later on, the UK based dental company Odontis developed the patented product, BioTooth¨, in 2004 and is awaiting additional clinical trials before putting this procedure on the market.

The researchers’ main difficulty was controlling the size and shape of the newly formed tooth. After 3 years of research, scientists at Odontis learned which genes were responsible for tooth type and size. This was a major breakthrough that brought them several steps closer to applying the technology to humans. Since, the scientists at Columbia have considerably perfected the technique of stem cell teeth regeneration.

“…a new technique pioneered in the Tissue Engineering and Regenerative Medicine Laboratory of Dr. Jeremy Mao, Edward V. Zegarelli Professor of Dental Medicine, and a professor of biomedical engineering at Columbia University, can orchestrate the body’s stem cells to migrate to three-dimensional scaffold that is infused with growth factor. This can yield an anatomically correct tooth in as soon as nine weeks once implanted in the mouth.“These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo,  and by cell homing without cell delivery,” Dr. Mao and his colleagues said in the paper.“The potency of cell homing is substantiated not only by cell recruitment into scaffold microchannels, but also by regeneration of a putative periodontal ligaments newly formed alveolar bone.” (7)

The Happiness Medicine Institute’s Assessment

Dr. Jeremy Mao, Co-Director at the Center for Craniofacial Regeneration and professor of dentistry at Columbia University Medical Center, is the first to succeed in using stem cells in the regrowth of adult teeth. His new device acts as a scaffold, covered in growth-factor and guiding a patient’s stem cells to form a new tooth. The resulting formation is correctly shaped and properly merged into the anatomy of the mouth. This amazing regeneration takes only nine weeks. (Cf Exhibit A)

Section C

Perspectives and Clinical Trials regarding Dental Regeneration

At present, there are just a few clinical trials related to dental stem cells, two illustrations of which are reproduced below. (Exhibit C) These trials are still  testing the feasibility of the stem cells and the tolerance of the stem cell implantation. The latest scientific journal i found describes the update as follows, in pertinent parts.

“Numerous preclinical studies have shown that dental stem cells improve bone augmentation and healing of periodontal diseases. Clinical trials are ongoing to validate the clinical feasibility of these approaches. Dental stem cells are also important for basic research. Expert opinion: Dental stem cells offer numerous advantages for tooth repair and regeneration. Data obtained from different studies are encouraging. In the next few years, investigations on dental stem cells in basic research, pre-clinical research and clinical studies will pave the way to optimizing patient-tailored treatments for repair and regeneration of dental tissues”  (Source) (8)

Thus, it looks like we have to wait a little more before our own stem cells can spur a “third” dentition. One trial in China is using stem cells from human exfoliated deciduous teeth (SHED) as the main target for investigation. Investigators from China are aiming to explore and clarify if autologous (cells or tissues obtained from the same individual) SHED stem cell transplantation can efficiently regenerate pulp (the center part of a tooth) and periodontal (connective tissue known as gum) tissue in immature permanent teeth and necrotic pulp of teeth in humans. (9)

 

Other Applications of Dental Stem Cells

Dental stem cells can differentiate into several cell types, such as neurons, adipocytes, and chondrocytes. From that, their therapeutic potential has been identified for various conditions, including neurological disorders, angiogenesis and vasculogenesis, liver disease, diabetes mellitus, and for regenerative ocular therapy, bone tissue engineering, and, of course, therapeutic applications in dentistry such as regenerative endodontic therapy, dentin regeneration, regenerative periodontal therapy, and bioengineered teeth. In this perspective, the French are using dental stem cells for bone regrowth while the Australians are experimenting dental stem cells for post stroke disability.

French Scientists are experimenting on dental stem cells for bone regrowth

One of the main limitations in bone regeneration is lack of vascularization within bone tissue. A new trial starting in France is aiming to use the dental stem cells of a simple and non-invasive tissue source such as dental pulp to develop a brand new pre-vascularized tissue-engineered bone construct. The dental pulp stem cells were isolated from the dental tissue of patients’ wisdom teeth and then used to assess their endothelial and osteoblastic differentiation to obtain pre-vascularized tissue engineered bone construct. Furthermore, one commercial differentiation medium is also used to evaluate its effect on the cell differentiation and production of a prevascularized bone construct.

Australian scientists are experimenting with dental stem cells to treat post-stroke disability

TOOTH (The Open study Of dental pulp stem cell Therapy in Humans), a clinical trial protocol, is an open study, phase 1, single-blind clinical trial being conducted by Australian researchers. The protocol is investigating the use of dental pulp stem cell therapy for stroke survivors with chronic disability, with the aims of determining the maximum tolerable dose of the cell therapy, and the safety and feasibility for patients with chronic stroke

 Is this Dental Stem Cell Teeth regeneration Technique Cost-friendly, Safe and Efficient ?

The technology behind the procedure has already been patented and Dr. Mao is now pursuing clinical trials. According to  the following source, currently, a single implant goes from 2,400 dollars all the way up 10,000 dollars depending on the complexity thereof.  (Source)Couple of years ago, these stem cell implants were expected to cost around $2500-3500. (10) I have not seen any recent price updates. Thus it would appear that this dental technique would be overall either cheaper or the same price as conventional implants. And without the ill effects of implants.

Furthermore, from the Clinical Trials that i read, this technology appears to be safe. And from the preclinical and animal studies that i examined, this technique also appears to be efficient and long lasting. In other words, there would be no need to replace the new tooth with another procedure, contrarily to most of today’s organ replacements.

How Do Stem Cell teeth Regeneration Procedures compare to Implant Procedures ?

Stem cell dental procedures would require post-op care as tooth extractions, but that does not appear to be expensive, especially if the patient uses holistic methods to make sure there is no infection (Eugenol rich clove essential oil being one of the best).

Comparatively, a stem cell implant would require only a local anesthetic only. Acupuncture or cannabis sedation could suffice. Up to the patient and the dentist to decide. Stem cell tooth implants would also be healthier and a more comfortable alternative to dentures. Unlike dentures, the newly developed teeth would move with the mouth, conserving the health of the gums. With this stem cell technique, the body’s meridian system would also be less perturbed, as would the nerves and pain receptors. In effect, drilling holes to screw implants in jaw bones can be quite invasive. The Stem cell technique would also help to avoid the patient’s mouth to experience metal galvanic effects and other inconveniences from metal implants.

When will this technology be available ?

Experimentation is still ongoing, but this teeth regeneration via dental stem cells technology is promising, perhaps operational in the US within two years and all the more so that there would not be the ethical concerns that embryonic stem cells can invoke.

We are still awaiting written response from Columbian dental school to get informed on the latest in terms of human clinical trials and clinical practice and when this technology would be available.

How can the viewer better understand this procedure

See Exhibits B for some diverse video explanations on the procedures that govern this technology. To grow a new tooth  with one’s own stem cells in one’s own tooth socket where the tooth will integrate with surrounding tissue in ways that are impossible with hard metals or other materials is indeed quite a medical revolution in the art of dentistry. It is much more holistic as a procedure than what allopathic dentistry offers, thus, the System of Things may delay clinical progress.

Discussion

Like with certain lifespan extension procedures, the effective availability of regenered teeth via stem cells is a matter of time. Preclinically, dental stem cells have been abundantly grown in petri dish from human dental stem cells. (See picture above). Rats and mice also grew back their removed teeth with this dental stem cell technology. For this technique to become the new standard of care for falling teeth, a fair amount of clinical trials usually needs to be successfully finished and then the Dentistry Industry will need to do some adjustments, all of which may take a few more years given the industry’s vested interests in implants, root canals and other inferior procedures. However, this technology may be available in less bureaucratic countries. Stem cell tooth implantation should thus be the new dental standard of care in the near future, notwithstanding the Dental Industry’s stubborn “vested interests” (ie, the dogmas and financial interests relative to mercury fillings, industrial toxic fluoride toothpaste, BPa sealants and their consternating estrogenic impact, inter alia, the issue of crowns, root canals, in particular with regard to carcinogenesis, among other non holistic procedures). (11)

What about Tooth Storage for future use ?

There are an increasing number of Teeth Banks that will cyrofreeze and harvest dental stem cells for future use, especially baby teeth, tagged at around 1800 dollars for the initiation fee and over 100 dollars yearly storage fee. So far, we don’t seem to have evidence that in 20 years, these stem cells will be viable. Cyrofreezing appears to work for the first few year, but uncertain for long durations.

What about placing a falling teeth or baby’s placenta in house freezer for future stem cell use ?

That probably would not work, as with normal freezing,  crystals would pierce the cell membrane of stem cells, so that when the cells are thawed,  the cytoplasm would leak out through the holes and the cell would die.

Furthermore, freezing cells requires may require additives to modify the structure of water so that no crystals are formed.  The most common chemicals appear to be dimethyl sulfoxide and glycerol. However,  even with the right additives, cells do not survive in an ordinary freezer very long. Storage of cells is done at -80° C or at liquid nitrogen,  -196° C. Even at -80°, the cells are viable for only about 5 years.

Lyophilozation ?

Lyophilization (or freeze-drying) is the process of drying a frozen sample, from which frozen water is removed via sublimation, by transiting ice directly to the gas phase without passing through the intermediate liquid phase.  Lyophilization has a long history of successful use in different areas of medicine and the food industry, but until recently lyophilization methods were not suitable for cell preservation. Easier to preserve DNA than cells. Nonetheless, Osiris Therapeutics, Inc. has developed a lyophilization method that preserves living cells in tissues, allowing storage at room temperature for prolonged times without loss of cell viability.  Preliminary results show that this method is reproducible, scalable, and can be applied to a variety of living cell and tissue types. The first commercial implementation of this lyotechnology will be for products containing placental cells. The full potential of lyotechnology is still under study and development. The ability of this method to preserve vascularized tissues and organs must be investigated. The optimization of cell manufacturing and cell storage with lyotechnology will take time. However, it is expected that lyotechnology will have a positive impact to expand the widespread use of cellular therapies, and may revolutionize cell and tissue banking.

Conclusion

Over 35 million Americans have lost all of their natural teeth from one or both jaws and about 178 million adults are missing at least one tooth, inter alia, according the American College of Prosthodontists. (12) These figures suggest that there is a “losing teeth” epidemic, because with proper eating and holistic living, teeth don’t normally fall out, Weston Price among others spent his adult years fixing and studying teeth all around the world and found near perfect teeth among indigenous elders who lived more holistically than today’s modern Westerner. Different studies have also shown that the absence or minimizing of teeth loss is a biomarker for longevity. (Source)

Many people with tooth loss opt for expensive implantation procedures. Commonly made of titanium, implants take as long as several months to heal and if the metal screw doesn’t fuse with the jaw over this time, it will fall out. Furthermore, titanium is not an innocent heavy metal, it can impact the body’s delicate fine-tuning. In effect, there are many problems with the implant industry, (13) all of which could disappear once this new dental stem cell technology is available to the public.

Furthermore, as we saw, human exfoliated deciduous teeth stem cells can also be used for other organs. Usually, the dental stem cells that are used for teeth regeneration come from the wisdom teeth, so it may be all the wiser to keep one’s wisdom teeth that their removal can precipitate excavation and infection problems.

What we have known for many years is that dental stem cell teeth regeneration therapy via injection consistently works with mice and rats. We also know that electro-medicine can spur the regeneration of teeth. I remember hearing in a conference the case of an elder lady who grew two new teeth as a result of getting zapped by lightning. Malignant tumors have also shrunk and even disappeared with a good zap from the Sky’s lightning.  This avenue, (but with more gentle zapping) should be better explored, including with laser and electro-acupuncture. Certain animals like sharks and crocodiles regenerate their teeth with stem cells continuously, on demand and without getting zapped by the Ocean’s thunder storms. When they get into a fight and lose teeth, new ones grow quickly back for the next round of sparring. Human boxers don’t have the DNA instructions to replicate this animal feat. So maybe they shouldn’t box, especially knowing that TBIs (traumatic brain injuries) trigger serious mental disorders. Today, despite the Industry’s inertia, inspired teeth experts have found a way to tweak a patient’s own dental stem cells to grow new teeth. Tentative conclusion: Holistically inspired human dental technology may have similar effects as Nature’s DNA with regard to crocodile and shark teeth regeneration. (*)

Ch Joubert (HMI director)

Exhibit A

Columbia University’s Teeth Regeneration Breakthrough

COLUMBIA UNIVERSITY MEDICAL CENTER, NY, USA. Human molar scaffolding is a technique that directs the body’s stem cells into scaffolding that will assist in regenerating a new tooth. This innovation can immensely alleviate the need to go through the painful, expensive and tedious process of dental implants.

Edwin S. Robinson Professor of Dentistry at Columbia University and Co-Director for the Center for Craniofacial Regeneration, Dr. Jeremy Mao has developed a growth factor-infused, three-dimensional scaffold that has the capability of regenerating an anatomically correct tooth in a span of 9 weeks from the date of implantation. He used a method that was developed in the university’s Tissue Engineering and Regenerative Medicine Laboratory. He can direct the body’s own stem cells towards the three-dimensional scaffold which is made of natural materials. Hence, the stem cells will naturally colonize the scaffold, enabling a tooth to grow in the socket and merge with the surrounding tissue.

Dr. Mao’s technique has successfully eliminated the need to grow new teeth in a Petri dish. Also, it is the first technique ever to successfully achieve the regeneration of an anatomically correct tooth with the use of the body’s innate resources. This method definitely has a faster recovery time compared to current dental implant procedures. Also, its natural process of regeneration is more appealing and enticing. Currently, Dr. Mao is testing different ways in applying his technique to make it more cost-effective in clinical therapies.(Source)

Exhibit B

On Dental Stem cell Research

Exhibits C

Clinical Trials

Ct Ending in 2020

 “This is a controlled clinical trial designed to evaluate the survival of mature permanent teeth with apical lesion treated with regenerative endodontic procedure (REP) based on encapsulated Mesenchymal Stem Cells in a biological scaffold. The REP will be compared to the conventional endodontic therapy. The REP is based on the use of umbilical cord-derived mesenchymal stem cells encapsulated in a plasma-derived biomaterial . The study group will use the disinfection protocol, indicated in the clinical considerations for regenerative procedures as recommended by the American Association of Endodontics, using a paste of calcium hydroxide prepared with double-distilled water as intracanal medication, and will be operated with REP using allogeneic stem cells in a scaffold, while the control group will be operated with conventional endodontic therapy alone. This clinical trial pretends to determine the dental survival of the tooth with mature apex and apical lesion, over a period of 2 years. (Source)

Ct Ending in 2017

“In this randomized controlled trial, 29 chronic periodontitis patients presenting one deep intrabony defect and requiring extraction of one vital tooth were consecutively enrolled. Defects were randomly assigned to test or control treatments which both consisted of the use of minimally invasive surgical technique. The dental pulp of the extracted tooth was mechanically dissociated to obtain micro-grafts rich in autologous DPSCs. Test sites (n=15) were filled with micro-grafts seeded onto collagen sponge, whereas control sites (n=14) with collagen sponge alone. Clinical and radiographic parameters were recorded at baseline, 6 and 12 months postoperatively”. (Source)

Ct that ended in 2014

The purpose of this clinical trial is to both clarify the efficiency of autologous periodontal ligament (PDL) stem cells to regenerate periodontal tissue in periodontitis patients with deep intraosseous defects (>5 mm) and to confirm the safety of using autologous stem cells in clinical periodontal regenerative medicine. This is a single-centre, randomized, placebo-controlled study. This study has been approved by the ethical committees of School of Stomatology, Fourth Military Medical University. The study will be conducted according to the Declaration of Helsinki.

Primary Outcome Measures :

  1. Periodontal bone regeneration [ Time Frame: 1 year ]
    The main outcome measures in the study protocol were: rate of increase in alveolar bone height and millimeter of clinical attachement level (CAL) regained. In addition, we examined whether and to what extent adverse events, for which causal relationships with the use of PDL cell were not ruled out, emerged. We set rate of increase in alveolar bone height as the most statistically important outcome (primary outcome).

Secondary Outcome Measures :

  1. Clinical parameters [ Time Frame: 3 months -12 months ]
    pocket depth (PD), attachment level (AL), and tooth mobility (TM) (Source)
olfactoryDog
Top: This Dog shows us his-her olfatory bulb receptors. These are connected to meridians that share similar energy pathways as teeth meridians. In biology, everything is connected to everything.
 Post Under construction

 Reference and Precision Notes

(1).  Keishi Otsu, Mika Kumakami-Sakano, Naoki Fujiwara, Kazuko Kikuchi, Laetitia Keller, Hervé Lesot, and Hidemitsu Harada (February 4, 2014). “Stem cell sources for tooth regeneration: current status and future prospects”. Frontiers in Physiology 5: 36.
(2).  Hill, David J. (2012-05-10). “Toothless no more – Researchers using stem cells to grow new teeth”. Singularity Hub. Retrieved June 16, 2014.
(3).  http://undergroundhealthreporter.com/tooth-regeneration-now-possible-with-new-stem-cell-research/#ixzz3yHaTt0UB
(4). Ibid.
(5).K. Kim, C. H. Lee, B. K. Kim, J. J. Mao. Anatomically Shaped Tooth and Periodontal Regeneration by Cell Homing. Journal of Dental Research, 2010 See also http://dental.columbia.edu/news/body-s-own-stem-cells-can-lead-tooth-regeneration. This study is published in the most recent Journal of Dental Research, a peer-reviewed scientific journal dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry, the oral cavity and associated structures in health and disease.
(6).  Young CS, Terada S, Vacanti JP, Honda M, Bartlett JD, Yelick PC (2002). “Tissue engineering of complex tooth structures on biodegradable polymer scaffolds.”. J Dent Res 81 (10): 695–700.
(7). http://www.dentistryiq.com/articles/2010/05/body-s-stem-cells.html
(8). Expert Opin Biol Ther. 2018 Feb;18(2):187-196
(9). Millions of teeth are accidentally and forcibly detached each year, especially causing losses of immature permanent teeth in children. This clinical trial is starting to recruit patients with immature permanent teeth and pulp necrosis. SHED will be used as the cell source for regenerating pulp and periodontal tissue in immature teeth.  Stem cell therapies have great potential to  cure currently untreatable diseases and to even extend lifespans. Due to their differentiating qualities, they have been used for novel regenerative protocols. Ongoing progress towards the clinical use of dental pulp stem cells has recently expanded the possibilities for clinical applications based on pulp and periodontal tissue regeneration. Dental stem cells are a kind of mesenchymal cell that reside within the dental pulp and are classified as postnatal stem cell populations.
(10). Mercury fillings have been amply shown to be toxic and carcinogenic as well as fluoride (also leading to osteosarcoma and lower I.Q.) while root canal’s anaerobic bacteria have frequently been responsible for cardio-vascular events, inter alia. The evidence, for another time.
(11). Op cit. Underground health report.
(12). The Data: “More than 35 million Americans are missing all their teeth in one or both jaws. 15 million people in the U.S. have crown and bridge replacements for missing teeth. 3 million have implants and that number is growing by 500,000 a year. 10 percent of all US dentists place implants but that is increasing. Implants performed by US dentists: The global prosthetic supplies market is projected to reach $4 billion by 2018.  The dental implant and prosthetic market in the U.S is projected to reach $6.4 billion by 2018. (Source)
(13) Dental implants is the most rapidly increasing area of dentistry, growing 15-20% every year. But just as with other dental procedures, there are major inconveniences and risks with this surgical dental procedure. It is  executed in stages and entails several procedures, many of which can be painful. Artificial implants carry many risks, from infection, to nerve damage, sinus and circulatory issues as well as the risks of general anesthesia. Furthermore, the healing process can  take up to 18 months and  the implants can refuse to align with the jawbone and end up falling out
(*). This article was written in January, 2016, but I have updated it, in particular Section C today, early 2018 .

Screen Shot 2016-01-24 at 12.25.53 PM

Copyright (c) 2016. Happiness Medecine Institute and agents. All rights reserved
Disclaimer: Nothing in this educational blog should be construed as medical advise.

Professor Joubert teaches in different parts of the world how to extend a healthy Lifespan to 120 years and beyond. Working on a Documentary and book that redefines Medicine in light of new discoveries, ancient wisdoms, innovative research and holistic science, he can be nonetheless available to coach patients back to homeostasis, wellbeing & Joie de Vivre. On occasion, Pr. Joubert can also coach health professionals to better protect their holistic practice when they must deviate from outdated and irrational mainstream “standards of care”. See links on “Contact” and “Mission” (under the “About” link) for details.

Posted in Dentistry, Oral Health & Wellbeing, Homeostasis, Self-Repair Mechanisms, Autophagy, Bio-Terrain, Microenvironment, Stem cells, Differentiation, Genomic Instability Biology
2 comments on “Dental Stem Cells Grow New Teeth
  1. David Baldwin says:

    Will they be able to grow parts of your existing teeth to replace artificial tooth fillings?

  2. Gean says:

    Hi, is this tooth regeneration procedure now available for patients in dental practices in the US?

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