Stem Cell Overview
Stem cells have been defined and discussed in
medical journals for more than a century.1 Simply
stated, stem cells are undifferentiated or non-specific
cells that not only have the capacity for selfrenewal,
but also have the ability to produce the
differentiated or specific cells needed for a variety of
tissue regeneration and therapeutic applications.
A significant amount of the media coverage of
stem cells has been devoted to the highly controversial
variety of stem cells that are harvested from
human embryos. While the potential of embryonic
stem cells is enormous, the controversy surrounding
the use of these cells has clouded the perception
of consumers and health-care professionals to
the point that the term "stem cell" is frequently
thought to be synonymous with "embryonic stem
cell." As a result, the positive developments in stem
cell research and preservation using alternative
sources that are not linked to a highly personal and
oftentimes emotional ethical debate are often lost
in the confusion.
Other less controversial sources for stem cells
research and clinical application currently in use are
bone marrow, peripheral blood stem cells, adipose
tissue, and umbilical cord blood cells. Each has its
distinct advantages and disadvantages.
Bone marrow stem cells have been primarily
used since the 1950s for treatment of leukemia and
genetic blood disorders.2 Today, an estimated
50,000 bone marrow transplants are performed
every year,3 and more than 1,500 clinical trials
regarding bone marrow stem cells are either
planned, in progress or have been completed for therapeutic applications ranging from treating
leukemia to spinal cord injuries.4
Bone marrow stem cells will continue to grow in
importance for regenerative medicine, as these new
therapeutic applications come online, but they are
not without problems; an invasive surgical procedure
is needed to harvest bone marrow stem cells
that is somewhat painful and not without risks for
the donor. In addition, donor and recipient matching
remains a challenge – especially when time is of
Over the last 20 years, peripheral blood stem
cells have become commonly used as a source of
hematopoietic stem cells for a bone marrow transplant.
Donors are given a growth factor for four or
five days to stimulate the release of stem cells into
the bloodstream, and peripheral blood stem cells are
then collected from the donors" blood by a process
called apheresis or leukapheresis. The collection of
peripheral blood stem cells is associated with some
side effects, but follow-up studies have not yet
found any significant increase in long-term health
risk for the donor.5
Adipose tissue is another source of stem cells,
which are commonly obtained from liposuction
aspirates or abdominoplasty procedures. They are
currently being researched to determine their stem
cell viability and potential for a wide range of therapeutic
applications, including diabetes, heart failure
and arthritis, to name just a few.6
In reconstructive surgery, adipose tissue stem cells
are being explored for the repair of tissue defects
resulting from traumatic injury, tumor resection and
congenital defects,7 as well as from calvarial defects
following severe head injury.8 Potential dental applications
include maxillary and mandibular repair.9
As with bone marrow stem cells, the biggest downside
of adipose tissue stem cells might be the need for
an invasive procedure to harvest the stem cells, with
the associated pain and risk of adverse events.
A convenient source of stem cells is umbilical
cord blood. Cord blood collection is a non-invasive
procedure performed at birth, and is easily integrated
into the childbirth process, but the window
of opportunity is small, as the cord blood must be
collected at the time of a child"s birth and preserved
Since the mid-1980s, the clinical applications
for cord blood stem cells have expanded to the point
where dozens of diseases can be treated with fresh or
cryopreserved cord blood. In fact, more than 9,300
patients have been treated with stem cells derived
from umbilical cord blood, with 200,000 units
being publically banked.10
The rate of consumer adoption of cord blood
banking is very impressive, with 550,000 units privately
banked to date by parents upon the birth of
their children.11 The growth in private cord blood
banking was originally driven by consumer
demand, and over time has become recognized as an
option that parents need to be fully informed of in
order to make an intelligent decision. The need for
health professionals to educate their patients led the
American College of Obstetrics and Gynecology to
issue guidelines for informing parents, noting that
some states have passed legislation requiring that
parents be informed of their options.12
One Dentist's Dental Stem Cell Discovery
Dr. Nicholas Perrotta is a general dentist who practices full-time in Medford, Massachusetts. Dr. Perrotta
became an advocate of dental stem cell preservation in his practice after conducting his own research
as a consumer and opting to preserve the stem cells of his 13-year-old daughter and 10-year-old son.
According to Dr. Perrotta, cord blood stem cell preservation was not widely discussed when his daughter
was born in 1998, but he and his wife had planned on banking his son's cord blood stem cells in 2001.
"However, because he was born prematurely, we missed the opportunity, and later regretted it."
In 2004, he read an article published by the National Institutes of Health that explained the potential of
preserving dental stem cells, and he recognized this as a possible new opportunity to preserve the stem
cells of his children. "I was also very encouraged by other emerging research regarding the use of
dental stem cells to repair damaged tissue," explained Dr. Perrotta.
From that point, he conducted his own extensive research into dental stem cells and the subject of
biobanking. "I wanted to be sure that the biobanking facility that would be storing my children's
dental pulp stem cells was reputable, financially stable and followed best practices when it came to
long-term stem cell storage," explained Dr. Perrotta.
He found the company that provided the best overall solution and the one he chose to bank his own children's
samples with was Provia Labs, which provides the Store-A-Tooth dental stem cell banking service.
Dr. Perrotta decided to offer his patients the option to bank their own dental stem cells in the very early
stages, in 2005. "First of all, I figured that if I chose this option for my own children, why not at least offer
the same option to my patients? I also see the dental business model following that of OB/GYN practitioners
and cord blood storage: These doctors were on the front lines of patient education and helped explain
in simple terms the potential benefits of banking autologous stem cells. I believe dentists like me will
serve the same educational role in the increased acceptance of dental stem cell storage," Perrotta said.
The fact that it appears the first applications for dental stem cells will be in the dental field is especially
exciting to Dr. Perrotta. "The potential for using dental stem cells to grow teeth, bone and dental
pulp is helping dentistry evolve from a restorative to a regenerative discipline. Dental stem cells
represent an enormous opportunity for the field of dentistry to provide improved care to our patients.
The implications of this I think we still do not fully appreciate yet."
How can dentists successfully introduce dental stem cell preservation into their practices? "They have
to be believers," says Dr. Perrotta. "Then they have to carefully educate the rest of the staff – especially
the hygienists." Dr. Perrotta conducted a series of lunch-and-learns with his staff, armed with
educational materials that he downloaded from www.store-a-tooth.com.
|"Our hygienists are the ones who introduce and explain the Store-A-Tooth program to our patients, especially
those with children. They give them a brochure, have them watch a video and also encourage them
to do their own online research to determine whether or not dental stem cell research is right for their
families. There is no hard sell, just alerting them of the existing option of dental stem cell preservation.
The hygienists in my practice appreciate being able to offer patients this service option."
If a patient is interested, the process is simple. They request a Store-A-Tooth collection kit from Provia
Labs, bring it to Dr. Perrotta's office for the extraction, and the tooth is sent overnight by 10 a.m. the
next day to Provia Labs' biobanking facility. "It's very simple, non-invasive and affordable, with consumer
interest in dental stem cell preservation growing every day, thanks to increasing news and scientific coverage
of dental stem cells. I can offer access to expanded services without carrying any extra inventory.
"To those who think it is too early to bank dental stem cells," Dr. Perrotta says, "science and technology
will continue to evolve quickly over the next few years. We can help the patients save these tissues today.
Researchers are looking at amazing treatments in human and animals such as treating spinal cord injury. This gives patients an opportunity to store
dental stem cells from a tooth that otherwise would be discarded. In the end, our obligation as dentists is to provide our patients with the access to the
best dental technology and services possible. Store-A-Tooth puts us in the forefront of dentistry and regenerative medicine."
Dental Stem Cells: Cord Blood 2.0?
Given this landscape acknowledging the need
for informed consumer choice, we anticipate that
dental professionals will play an instrumental role in
driving increased consumer acceptance and adoption
of dental stem cell preservation.
Leading the charge might be a subset of the dental
profession – pediatric dentists. In fact, as early as
2008, the American Academy of Pediatric Dentistry
issued the following statement:
The American Academy of Pediatric Dentistry
recognizes the emerging field of regenerative medcontinued icine and encourages dentists to follow future evidence-
based literature in order to educate parents
about the collection, storage, viability and use of
dental stem cells with respect to autologous regenerative
By following this recommendation, pediatric dentists,
general practitioners and virtually any dental
specialist can help propel the growth of regenerative
medicine, an emerging field identified by the U.S.
Department of Health and Human Services13 that is
already making us rethink the current roles of healthcare
professionals. Regenerative medicine might enable
the treatment of diseases that are incurable at the
present time, which in turn will create a new industry
with potentially strong economic impact.14
Moreover, the increased acceptance of dental
stem cell preservation will put the dental professional
at the forefront of an interdisciplinary and
more integrated healthcare industry working
towards the common goal of repairing, replacing, or
enhancing biological function compromised due to
congenital deformities, injury, disease and aging.
Why Dental Stem Cells? Why Now?
Dental stem cell research originating from the
National Institute of Dental and Craniofacial
Research and replicated worldwide has proven that
odontogenic tissues are a viable source of mesenchymal
stem cells (MSCs), especially the dental pulp of
third molars15 and exfoliating deciduous teeth.16
What"s more, the supply of these odontontic tissue
resources is enormous and generally untapped at
the present time. For example, it is estimated that
each year in the United States, there are 80 million
exfoliating deciduous teeth, 1.5 million extracted
pre-molars and 1.3 million extracted third molars.17
Most of these exfoliated and extracted teeth are
merely discarded, when they can be easily collected,
processed and cryopreserved in a quality
biobanking facility in preparation for future regenerative
The future of medical applications for dental
stem cells currently being studied is very exciting,
with the potential of helping countless number
of people afflicted with a range of conditions,
from type 1 diabetes, muscular dystrophy, stroke,
Parkinson"s disease, spinal cord injuries and
corneal injuries. Also on the horizon are prospective
regenerative applications for cranial defects,
bioengineered teeth, liver disease, myocardial
infarction and more.
While the potential medical applications
of dental stem cells are encouraging, several
dental and oral health applications have
already been evaluated, positioning the
dental professional to leapfrog other
health-care providers to be the first to introduce the
benefits of regenerative medicine to their patients.
Here are two examples of what is on the horizon:
- Alveolar bone regeneration (seeding bone cavities
with dental stem cells in a collagen matrix)
- Periodontal tissue repair (replacing diseased
gingival tissue with stem cells derived from
In a less than a decade from their discovery, dental
stem cells had been used in two human studies,
and new research and clinical developments continue
to help the potential evolve into reality.
There are many opportunities for collection of
dental stem cells during childhood: they can be collected
ancillary to routine dental procedures, and
they can be preserved in long-term storage at a relatively
affordable cost. They are suited for autologous
use, meaning the adult stem cells can be collected
from and used on the same person, so there are no
issues of immunological or genetic incompatibility.
Taking it to the (Bio)Bank
Here is how dental stem cell collection and storage
Once the dentist or hygienist collects the tooth,
it is transported from the office to the laboratory.
The tooth should always be transported via express
courier in a sterile, isotonic solution, and shipped
chilled to reduce the growth of contaminating
microbes. It should be noted that although stem cells
can be successfully recovered from teeth several days
post-extraction, the yield of viable cells can decline
significantly over time.18
Dental professionals should be certain that the
laboratory they use for dental stem cell storage has
validated processes with appropriate quality control
metrics in place, in order to verify its ability to
remove contaminating oral flora from the tooth and
to recover viable tissue.
Ideally, the laboratory should also have the ability
to grow these cells in culture and verify that the
cultured cells exhibit the baseline set of cell surface
markers required for mesenchymal stem cells.
The cryopreservation of stem cells typically
involves equilibrating the cells with a cryoprotectant
solution – a solvent that protects the cells from the
formation of ice crystals and also helps preserve the
integrity of cell membranes during the freezing and
The temperature is typically slowly brought
down to freezing using programmable controlledrate
freezers. Frozen stem cells are then transferred to
vapor-phase liquid nitrogen freezers for long-term
storage at ultra-low, stable temperatures at -150
degrees Celcius or lower.
The clinical use of cryopreserved tissues is currently
regulated at the state and federal levels.
Laboratories storing or expanding human cells for future clinical use must be registered with the FDA19
and often must be licensed by the department of
health of the state in which the laboratory operates.
A good sign of quality is if the laboratory is accredited
by the American Association of Blood Banks
and/or the American Association of Tissue Banks.
It is extremely important that dentists inquire
about the tooth transport system and the biobanking
facility used by any dental stem cell service provider
they are considering working with.
Teeth are clinically proven to be a source of
viable stem cells that may be used for the regenerative
treatment of a wide variety of medical and dental
Therefore, dentists are well positioned to
become one of the key providers of stem cells and
foster closer collaboration and convergence with the
The high-quality dental stem cell preservation
process begins with the dentist or oral surgeon, who
can be involved in the extraction, collection and
storage of the stem cells from their patients" teeth.
Ongoing research suggests that these stem cells will
be used first for dental applications, such as replacing
bone, periodontal ligaments, or dental pulp, and
to treat periodontal disease.
In order for dentists to fully participate in this
new role, which includes responsibility for providing
their patients with information regarding the option
of dental stem cell banking, they should utilize existing
information, including emerging research, to
become knowledgeable and conversant regarding the
applications, clinical use and banking of dental stem
cells. Ultimately, dental stem cell banking is an
option every eligible patient should know about.
- Ramalho-Santos M, Willenbring H. On the origin of the term "stem cell." Cell Stem Cell. 2007 Jun 7;1(1):35-8.
- Thomas ED, et al. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957;257:491-496.
- Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. 2007 Oct 11;357(15):1472-5.
- http://www.clinicaltrials.gov/ct2/results?term=bone+marrow+transplant. Accessed September 24, 2010.
- Hölig K, et al. Safety and efficacy of hematopoietic stem cell collection from mobilized peripheral blood in unrelated volunteers: 12 years of single-center experience in 3928 donors. Blood. 2009 114:3757-3763.
- Gomillion CT, Burg KJ. Stem cells and adipose tissue engineering. Biomaterials. 2006 Dec;27(36):6052-63.
- Lendeckel S, Jödicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, Hedrick MH, Berthold L, Howaldt HP. Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Craniomaxillofac Surg. 2004 Dec;32(6):370-3.
- Mesimäki K, Lindroos B, Törnwall J, Mauno J, Lindqvist C, Kontio R, Miettinen S, Suuronen R. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg. 2009 Mar;38(3):201-9.
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2801068/table/T2/. Accessed September 23, 2010.
- http://www.cordblood.com and http://www.viacord.com/general-faq.htm. Accessed September 23, 2010.
- Umbilical Cord Blood Banking. ACOG Committee Opinion No. 399. American College of Obstetricians and Gynecologists. Obstet Gynecol. 2008 111:475-7.
- Regenerative Medicine. Department of Health and Human Services. August 2006. http://stemcells.nih.gov/info/2006report/
- Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000 Dec
- Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, Shi S. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003 May
- American Dental Association. 2005-06 survey of dental services rendered. Chicago (Ill.): ADA; 2007.
- Perry BC, et al. Collection, cryopreservation, and characterization of human dental pulp-derived mesenchymal stem cells for banking and clinical use. Tissue Engineering. 2008
- Dominici, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006 8(4):315-17.
- http://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/QuestionsaboutTissues/ucm136323.htm. Accessed April 13, 2012.14(2):149-156.