|Year : 2019 | Volume
| Issue : 1 | Page : 1-6
Dental stem cells – Sources and identification methods
Anjali Narwal1, Shruti Gupta2, Anita Hooda2
1 Department of Oral Pathology, Pt. B. D Sharma University of Health Sciences Post Graduate Institute of Dental Sciences, Rohtak, Haryana, India
2 Department of Oral Anatomy, Pt. B. D Sharma University of Health Sciences Post Graduate Institute of Dental Sciences, Rohtak, Haryana, India
|Date of Submission||15-Jul-2018|
|Date of Decision||23-Aug-2018|
|Date of Acceptance||11-Nov-2018|
|Date of Web Publication||14-Feb-2019|
H. No. 166, Old PLA Sector, Hisar - 125 001, Haryana
Source of Support: None, Conflict of Interest: None
The banking of mesenchymal cells from the umbilical cord and harvesting them for future use is the current trend in medical science. Such sources are reservoirs of stem cells. Over the past decade, the field of dentistry has embossed its presence by taking major lead in the field of regenerative medicine and more precisely in the field of stem cells. These stem cells have the capacity for regeneration and repair by converting into any other cell type. However, these cells require signals for differentiation in a timely manner. Tooth and its associated structures have been discovered as the latest reservoirs of stem cells. In this review, a light has been thrown on such sources and their identification has been emphasized.
Keywords: Pluripotent, reservoir, stem cells
|How to cite this article:|
Narwal A, Gupta S, Hooda A. Dental stem cells – Sources and identification methods. CHRISMED J Health Res 2019;6:1-6
|How to cite this URL:|
Narwal A, Gupta S, Hooda A. Dental stem cells – Sources and identification methods. CHRISMED J Health Res [serial online] 2019 [cited 2020 Jun 5];6:1-6. Available from: http://www.cjhr.org/text.asp?2019/6/1/1/252282
| Introduction|| |
Every year, billions of monies are spent for reconstruction of defects due to tissue loss or end-stage organ failure. Regeneration of tissues holds a promising alternative for the reconstruction of defects in the head-and-neck regions. Trauma, infectious diseases, inherited disorders, and neoplasms are the major etiological factor for the tissue loss in the craniofacial region. Various approaches have been considered in regenerative medicine, but currently, the most common is to use a “biodegradable scaffold in the shape of new tissue that is seeded with either stem cells or autologous cells from biopsies of damaged tissues.” These seeded autologous or stem cells are pluripotent in nature, and under appropriate microenvironment, they differentiate into any cell type.
Due to developmental similarities with other organs such as the hair, kidney, and lungs, teeth are considered to be excellent models for studying organ regeneration and also they are clinically accessible and convenient for experimental research. Within the next 25 years, advances are going to take place in regenerative medicine, and dentist will have a pivotal role in providing stem cells from dental tissues which will not only generate a new tooth but also hold the potential for the regeneration of many other tissues also.
Stem cells are the unspecialized cells which have the potential of self-renewal and differentiation into many other cell types. “Stemness is the ability of undifferentiated cells to undergo an indefinite number of replications and ability to give rise to any kind of specialized cells.” Differentiation can be appreciated microscopically by alteration in the morphology of cell as well as the presence of tissue-specific protein in its cytoplasm. Stem cells may remain dormant or silent over long periods of time until there is a physiological need for more cells to maintain tissues or they are activated by disease or tissue injury. Such self-renewal or actively dividing and differentiating sites of tissue are known by the name “stem-cell niches.” Such sites have been identified in the skin, adipose tissues, peripheral blood,, hair follicle, bone marrow, brain, intestine, pancreas, and teeth., Thus, the primary role of adult stem cells is to maintain and repair the tissue in which they are found. The branch of health sciences in which stem cells are retrieved from their niches, cultured, and harvested at the required site is known as stem cell science. It has led to introduction and establishment of translational techniques such as artificial skin therapies, target cell-based therapies in diabetes, atherosclerosis, and neurodegenerative diseases in which stem cells are grown at the diseased site. Stem cells are present in different tissues, but stem cells from bone marrow have always been a surgeon's favorite choice because of their pluripotentiality. The need for an alternative to conventional mesenchymal stem cells (MSCs) to more accessible cells has propelled the research toward dental tissues, which are a rich source for stem cells. The purpose of this article is to discuss the source, nature, and phenotype of dental stem cells.
| Basic Properties of Stem Cells|| |
- They are undifferentiated cells, that is, they have not developed into a specialized cell types
- They have the capability to undergo multiple cycles of cell division while maintaining their undifferentiated state
- They have the ability to differentiate into specialized cell types.
| Types Of Stem Cells|| |
Stem cells are basically divided into three categories:
- Embryonic stem cells (ES cells) are derived from the blastocyst during embryonic development and are either totipotent or pluripotent in nature. They can give rise to all the three primary germ layers: ectoderm, endoderm, and mesoderm. In contrast to adult stem cells, ES cells have the ability to divide actively for self-renewal without any differentiation for longer time period. ES cells attain epigenetic marks in their DNA on meeting a suitable environment, so they can differentiate into specialized cells of the eye, liver, muscle, nerve, and bone, for example [Figure 1]
- Somatic or adult stem cells exist throughout the body in different tissues including the bone marrow, skin, peripheral blood, liver, retina, brain, blood vessels, pancreas, muscle, adipose tissue, and dental tissues. They can divide and give rise to another cell like itself but have a limited differentiation potential to other cell types. Their detection can pose a difficulty as they reside in specific heterogeneous sites with other supporting cells. Slow cell division of stem cells prove to be a boon in their separation from the other neighboring cells [Figure 2]
- “Induced pluripotent stem cell (iPS) is an evolving concept in which 3–4 genes found in the stem cells are transfected into the donor cells using appropriate vectors. The stem cells thus derived by culturing will have properties almost like ES cells.” They are pluripotent in nature. Yamanaka and Takahashi in 2006 cultivated first iPSs from adult mouse cells in their research laboratory. They succeeded in growing the iPS from human adult cells in 2007. iPS cells have similar properties of ES cells, that is, they have a capacity to divide indefinitely without losing the potential of differentiation into any cells of three germ layers., [Figure 3].
Stem cell identification
The common techniques used for easy identification of stem cells are as follows:
- Flow cytometer with specific stem cell antibody marker (fluorescent antibody cell sorting) – In this process, stem cells are identified by staining the stem cells with specific antibody markers and using flow cytometry
- Immunohistochemical staining
- Physiological and histological criteria including phenotype, chemotaxis, mineralizing activity, proliferation, and differentiation,
- Immunomagnetic bead selection – This method sort cells based on a highly expressed single surface marker using antibody-coated magnetic bead and magnetic field. This method have the combined advantage of high specificity of immunoassays and minimal invasiveness of magnetic force.
Stem cells express different protein markers on their surface and hence cannot be identified by a single protein marker. CD34 protein is well expressed by stem cells in the peripheral blood and umbilical cord, and hence, it can be used for their identification. Apart from CD34, hematopoietic stem cells express CD133, ABCG2, and Sca-1 which are used for identification. Markers which are helpful in identification of ES cells are Oct-3/4 and SSEMAs. MSCs are identified by their positive expression of CD105, CD13, and CD 73 genes and are negative for the hematopoietic markers such as CD34 and CD45.
| Stem Cells of Dental Origin|| |
The teeth act as an alternate source for stem cells as they have similar potency as that of bone marrow-derived mesenchymal cells. Potential sources of dental stem cells are as follows: dental pulp stem cells (DPSC), dental follicle stem cells (DFSC), stem cells from human exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), periodontal ligament stem cells (PDLSCs), and gingival stem cells (GING SCs) [Figure 4], [Figure 5], [Figure 6]. In spite of a common developmental pathway of dental tissues, it is still not fully understood whether these closely related tissues are programmed differently or not.
Dental pulp stem cells
Cells derived from dental pulp consist of heterogeneous population of progenitor cells that are also called odontoblastoid cells as these cells synthesize and secrete dentin matrix like the odontoblast cells of dentin., The source of odontoblastoid cells that replace the odontoblasts and secrete reparative dentin bridges is controversial. It has been suggested that odontoblastoids differentiate from the zone of Hohl cells which is a subodontoblstic cell-rich zone. A great deal of effort has been made in the past to isolate and identify the progenitor cells among them. DPSCs are lineage restricted with limited self-renewal and multilineage differentiation capability and stem cell count is comparatively low. Hence, there is a great challenge for them to become a practical stem cell resource for clinical application. They express positivity for CD9, CD10, CD13, CD29, CD44, CD49d, CD59, and CD73. Furthermore, they express CD90, CD105, CD106, CD146, CD166, STRO-1, Oct-4, Nanog, SSEA-4, and Vimentin.,,,,,,,, They have the in vivo capacity to form dental tissues (dentin and pulp) and mesenchymal tissues such as adipose and muscle. In vitro, they can differentiate into odontoblast, osteoblast, chondrocyte, adipocyte, myocyte, and neuronal cells., It has also been recognized that DPSCs play an important role in balancing inflammation and repair during invasive carious lesions or pulp exposures. This concept of balance has been investigated in vitro where it was seen that these cells migrate from perivasculature toward the dentin surface following injury to dentin matrix. DPSCs also express toll-like receptors 2 (TLR2) and TLR4 and vascular endothelial growth factor in response to lipopolysaccharide which is a product of Gram-negative bacteria.
Dental follicle stem cells
Dental follicle tissue acts as a source of DFSCs which have the ability to differentiate and form bone and cementum, and hence, they are used in periodontal and bone regeneration therapies. Human third molar teeth serve as a vital niche for DFSCs, and they have higher proliferation rate than that of DPSCs. They are easily available for cell culture and adhere well to the culture plates.
Stem cell markers such as Nestin, Notch-1, and STRO-1 are positively expressed in DFSCs. They also express positivity for cementum attachment protein and cementum protein-23 (cementoblast marker) as well as for bone morphogenetic protein 1 (BMP-1) and BMP-7. They express positivity for CD9, CD29, CD10, CD13, CD44, and CD49d. The positive expression for CD59, CD73, CD90, CD105, CD106, CD166, and HLA-Class I is definitely seen in DFSCs.,,,
Stem cells from human exfoliated deciduous teeth
This type of stem cells can be isolated from exfoliated deciduous teeth and have high proliferation capacity. They can differentiate into various cell types such as osteoblasts, neural cells, adipocytes, odontoblasts, endothelial cells, myoblast and chondrocyte,, and induce dentin and bone formation., They show positivity for CD13, CD44, CD73, CD90, CD105, CD146, Nanog, STRO-1, Oct-4, fibroblast growth factor 2 (FGF-2), Nestin, SSEA-3, SSEA-4, transforming growth factor-β (TGF-β), TGF-β2, collagen I (Col I), and Col III.,, SHED cells have higher proliferative index than DPSCs highlighting more immature population of multipotent stem cells. TGF-β1 and β2, FGF-2, and Col I and III are highly expressed in SHED as compared to DPSCs.
Stem cells from apical papilla
The dental papilla differentiates and matures into dental pulp during the early stages of odontogenesis. During root development, apical part of the papilla gets separated from pulp by cell-rich zone. This cell-rich zone constitutes SCAP cells. They are clonal cousins of fibroblast-like cells and have higher proliferation potential than DPSCs. SCAP cells express early mesenchymal surface markers, STRO-1, CD146, and CD24.
Periodontal ligament stem cells
Around 20 years ago, Melcher first proposed the concept of PDLSCs. These PDLSCs are the pool of progenitor cells such as fibroblasts, cementoblasts, odontoblasts, and osteoblasts. These cells exhibit 30% higher proliferative index as compared to bone marrow stem cells. They exhibit markers such as STRO-1, scleraxis, and also positivity for CD9, CD10, CD13, CD29, CD44, and CD49d. They also exhibit expression for CD59, CD73, CD90, CD105, CD106, CD146, and CD166.,, PDLSCs are the array of osteogenic markers such as bone sialoprotein, alkaline phosphatase, osteocalcin, and matrix extracellular phosphoglycoprotein and mesenchymal markers such as tendon marker scleraxis and STRO-1.
Gingival stem cells
On extensive literature search, two different types of adult stem cells have been identified in the oral mucosa. One of them is oral epithelial progenitor cells and other type is derived from the lamina propria of gingiva.,,
The cells derived from the lamina propria of gingiva are called gingival MSCs, gingival tissue-derived stem cells, gingival multipotent progenitor cells, and gingival margin-derived stem/proginetor cells, human oral mucosa stem cells, and oral mucosa lamina propria proginetor cells.,,, They have retained the capacity for multilineage differentiation and its related gene expression. They also have the capacity to differentiate into osteoblasts, chrondoblasts, adipocyte, endothelial, and neural cells. GING SCs proliferate faster than bone marrow-derived stem cells. They exhibit positivity for STRO-1, Oct-4, Sox-2, SSEA-4, Nanog, HLA-ABC, Nestin, Tra2-49, and Tra2-54. They also exhibit markers such as CD29, CD44, CD73, CD90, CD105, CD106, CD146, and CD166.,,,,
Aging of stem cell
After 120 days, MSCs start losing their proliferative potential in vitro expansion. Various changes occur in stem cells during culturing which including.
- Gradual decrease in proliferation index
- Shortening of telomere
- Functional impairment
- Typical Hayflick phenomenon of cellular aging.
“The Hayflick phenomenon is the number of times a normal human cell population will divide until cell division stops. Leonard Hayflick discovered 40 years ago that cultured normal human cells have limited capacity to divide, after which they become senescent, a phenomenon now known as the Hayflick limit.”,
Storage of stem cells
Adult stem cells are ideal source of autologous transplants, and they can be obtained from individuals at any age in life. Hence, to carry out such procedures, there is a need to store these stem cells which can be done by cryopreservation in liquid nitrogen (−196°C). These cells will survive at such low temperatures only if they are suspended in cryopreservatives/cryoprotectants. Cryopreservatives are necessary additives to stem cell concentrates, since they stop cell death by inhibiting the formation of intra- and extracellular crystals. Dimethyl sulfoxide is the standard cryoprotectant used in laboratories as it prevents freezing damage to living cells. Rapid freezing of stem cells prevent the ice formation in or around the cells and also plays a role in prevention of dehydration of cells.
| Conclusion|| |
In the recent years, the field of dentistry has embellished its presence by taking major hikes in research and bringing them into practice. The current focus of research in regenerative dentistry is on the isolation of stem cells from dental tissues, and these researches have provided a good deal of evidence that oral and maxillofacial regions are the good sources of stem cells. In the present time, stem cell banks have gain excessive popularity and stem cells from the umbilical cord are mainly preserved in these banks for future use. Thus, the dental professionals should recognize the importance of obtaining stem cells during routine procedures as they can be stored for regeneration therapies in the future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative endodontics: A review of current status and a call for action. J Endod 2007;33:377-90.
Potdar PD, Deshpande S. Mesenchymal stem cell transplantation: New, avenues for stem cell therapies. J Transplant Technol Res 2013;3:1-16.
Weissman IL. Stem cells – Scientific, medical, and political issues. N Engl J Med 2002;346:1576-9.
Scadden DT. The stem-cell niche as an entity of action. Nature 2006;441:1075-9.
Potdar P, Sutar J. Establishment and molecular characterization of mesenchymal stem cell lines derived from human visceral & subcutaneous adipose tissues. J Stem Cells Regen Med 2010;6:26-35.
Potdar PD, D'souza SB. Isolation of Oct4+, Nanog+and SOX2- mesenchymal cells from peripheral blood of a diabetes mellitus patient. Hum Cell 2011;24:51-5.
Potdar P, Subedi R. Defining molecular phenotypes of mesenchymal and hematopoietic stem cells derived from peripheral blood of acute lymphocytic leukemia patients for regenerative stem cell therapy. J Stem Cells Regen Med 2011;7:29-40.
Sedgley CM, Botero TM. Dental stem cells and their sources. Dent Clin North Am 2012;56:549-61.
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, et al.
Embryonic stem cell lines derived from human blastocysts. Science 1998;282:1145-7.
Fuchs E. The tortoise and the hair: Slow-cycling cells in the stem cell race. Cell 2009;137:811-9.
Chandra Mouli PE, Kumar SM, Senthil B, Partibhan S, Priya R, Subha R. Stem cells in dentistry – A review. J Pharm Sci Res 2012;4:1872-6.
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006;126:663-76.
Bansal R, Jain A. Current overview on dental stem cells applications in regenerative dentistry. J Nat Sci Biol Med 2015;6:29-34.
Sun C, Hsieh YP, Ma S, Geng S, Cao Z, Li L, et al.
Immunomagnetic separation of tumor initiating cells by screening two surface markers. Sci Rep 2017;7:40632.
Gajkowska A, Oldak T, Jastrzewska M, Machaj EK, Walewski J, Kraszewska E, et al.
Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells in leukapheresis product and bone marrow for clinical transplantation: A comparison of three methods. Folia Histochem Cytobiol 2006;44:53-60.
Park KS, Shin SW, Choi JW, Um SH. Specific protein markers for stem cell cross-talk with neighboring cells in the environment. Int J Stem Cells 2013;6:75-86.
Potdar PD, Jethmalani YD. Human dental pulp stem cells: Applications in future regenerative medicine. World J Stem Cells 2015;7:839-51.
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;97:13625-30.
Morsczeck C, Götz W, Schierholz J, Zeilhofer F, Kühn U, Möhl C, et al.
Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol 2005;24:155-65.
Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG, et al.
SHED: Stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A 2003;100:5807-12.
Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, et al.
Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 2006;1:e79.
Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al.
Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004;364:149-55.
Mitrano TI, Grob MS, Carrión F, Nova-Lamperti E, Luz PA, Fierro FS, et al.
Culture and characterization of mesenchymal stem cells from human gingival tissue. J Periodontol 2010;81:917-25.
Ponnaiyan D. Do dental stem cells depict distinct characteristics? – Establishing their “phenotypic fingerprint”. Dent Res J (Isfahan) 2014;11:163-72.
Wei X, Ling J, Wu L, Liu L, Xiao Y. Expression of mineralization markers in dental pulp cells. J Endod 2007;33:703-8.
Kitasako Y, Shibata S, Pereira PN, Tagami J. Short-term dentin bridging of mechanically-exposed pulps capped with adhesive resin systems. Oper Dent 2000;25:155-62.
Murray PE, About I, Lumley PJ, Franquin JC, Remusat M, Smith AJ. Cavity remaining dentin thickness and pulpal activity. Am J Dent 2002;15:41-6.
Iohara K, Zheng L, Ito M, Tomokiyo A, Matsushita K, Nakashima M. Side population cells isolated from porcine dental pulp tissue with self-renewal and multipotency for dentinogenesis, chondrogenesis, adipogenesis, and neurogenesis. Stem Cells 2006;24:2493-503.
Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, et al.
Stem cell properties of human dental pulp stem cells. J Dent Res 2002;81:531-5.
Lindroos B, Mäenpää K, Ylikomi T, Oja H, Suuronen R, Miettinen S. Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun 2008;368:329-35.
Zhang W, Walboomers XF, Shi S, Fan M, Jansen JA. Multilineage differentiation potential of stem cells derived from human dental pulp after cryopreservation. Tissue Eng 2006;12:2813-23.
Zhang W, Walboomers XF, Van Kuppevelt TH, Daamen WF, Van Damme PA, Bian Z, et al. In vivo
evaluation of human dental pulp stem cells differentiated towards multiple lineages. J Tissue Eng Regen Med 2008;2:117-25.
Ponnaiyan D, Bhat KM, Bhat GS. Comparison of immuno-phenotypes of stem cells from human dental pulp and periodontal ligament. Int J Immunopathol Pharmacol 2012;25:127-34.
Kawanabe N, Murata S, Fukushima H, Ishihara Y, Yanagita T, Yanagita E, et al.
Stage-specific embryonic antigen-4 identifies human dental pulp stem cells. Exp Cell Res 2012;318:453-63.
Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K. Stem cells in dentistry – Part I: Stem cell sources. J Prosthodont Res 2012;56:151-65.
Arthur A, Koblar S, Shi S, Gronthos S. Eph/ephrinB mediate dental pulp stem cell mobilization and function. J Dent Res 2009;88:829-34.
Yamagishi VT, Torneck CD, Friedman S, Huang GT, Glogauer M. Blockade of TLR2 inhibits porphyromonas gingivalis suppression of mineralized matrix formation by human dental pulp stem cells. J Endod 2011;37:812-8.
Lizier NF, Kerkis I, Wenceslau CV. Generation of induced pluripotent stem cells from dental pulp somatic cells. In: Bhartiya D, Lenka N, editors. Pluripotent Stem Cells. America: In Tech; 2013.
Shoi K, Aoki K, Ohya K, Takagi Y, Shimokawa H. Characterization of pulp and follicle stem cells from impacted supernumerary maxillary incisors. Pediatr Dent 2014;36:79-84.
Lindroos B, Mäenpää K, Ylikomi T, Oja H, Suuronen R, Miettinen S, et al.
Characterisation of human dental stem cells and buccal mucosa fibroblasts. Biochem Biophys Res Commun 2008;368:329-35.
Kémoun P, Laurencin-Dalicieux S, Rue J, Farges JC, Gennero I, Conte-Auriol F, et al.
Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro
. Cell Tissue Res 2007;329:283-94.
Völlner F, Ernst W, Driemel O, Morsczeck C. A two-step strategy for neuronal differentiation in vitro
of human dental follicle cells. Differentiation 2009;77:433-41.
Yalvac ME, Ramazanoglu M, Gumru OZ, Sahin F, Palotás A, Rizvanov AA. Comparison and optimisation of transfection of human dental follicle cells, a novel source of stem cells, with different chemical methods and electro-poration. Neurochem Res 2009;34:1272-7.
Nakamura S, Yamada Y, Katagiri W, Sugito T, Ito K, Ueda M, et al.
Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. J Endod 2009;35:1536-42.
Narang S, Sehgal N. Stem cells: A potential regenerative future in dentistry. Indian J Hum Genet 2012;18:150-4.
] [Full text]
Gay IC, Chen S, MacDougall M. Isolation and characterization of multipotent human periodontal ligament stem cells. Orthod Craniofac Res 2007;10:149-60.
Shi S, Bartold PM, Miura M, Seo BM, Robey PG, Gronthos S. The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res 2005;8:191-9.
Izumi K, Tobita T, Feinberg SE. Isolation of human oral keratinocyte progenitor/stem cells. J Dent Res 2007;86:341-6.
Venkatesh D, Kumar KPM, Alur JB. Gingival mesenchymal stem cells. J Oral Maxillofac Pathol 2017;21:296-8.
] [Full text]
Zhang Q, Shi S, Liu Y, Uyanne J, Shi Y, Shi S, et al.
Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol 2009;183:7787-98.
Tomar GB, Srivastava RK, Gupta N, Barhanpurkar AP, Pote ST, Jhaveri HM, et al.
Human gingiva-derived mesenchymal stem cells are superior to bone marrow-derived mesenchymal stem cells for cell therapy in regenerative medicine. Biochem Biophys Res Commun 2010;393:377-83.
Zhang QZ, Nguyen AL, Yu WH, Le AD. Human oral mucosa and gingiva: A unique reservoir for mesenchymal stem cells. J Dent Res 2012;91:1011-8.
Fawzy El-Sayed KM, Dörfer CE. Gingival mesenchymal stem/Progenitor cells: A Unique tissue engineering gem. Stem Cells Int 2016;2016:7154327.
Marynka-Kalmani K, Treves S, Yafee M, Rachima H, Gafni Y, Cohen MA, et al.
The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells 2010;28:984-95.
Tang L, Li N, Xie H, Jin Y. Characterization of mesenchymal stem cells from human normal and hyperplastic gingiva. J Cell Physiol 2011;226:832-42.
Wang F, Yu M, Yan X, Wen Y, Zeng Q, Yue W, et al.
Gingiva-derived mesenchymal stem cell-mediated therapeutic approach for bone tissue regeneration. Stem Cells Dev 2011;20:2093-102.
Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res 1961;25:585-621.
Lin NH, Gronthos S, Bartold PM. Stem cells and future periodontal regeneration. Periodontol 2000 2009;51:239-51.
Berz D, McCormack EM, Winer ES, Colvin GA, Quesenberry PJ. Cryopreservation of hematopoietic stem cells. Am J Hematol 2007;82:463-72.
Singh H, Bhaskar DJ, Rehman R, Jain CD, Khan M. Stem cells: An emerging future in dentistry. Int J Adv Health Sci 2014;1:17-23.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]