23 minute read
Stem Cells and Dentofacial Orthodontic Treatment Potential
Phimon Atsawasuwan, DDS, MSc, MSc, MS, PhD, is a tenured associate professor in the department of orthodontics at the University of Illinois Chicago and a diplomate of the American Board of Orthodontics. His research interest is focused on accelerated tooth movement, craniofacial/ bone biology, microRNA and advances in orthodontic treatment. Dr. Atsawasuwan’s research involves clinical research, bench-top molecular biology research, cell culture and animal research. Conflict of Interest Disclosure: None reported.Dentofacial orthodontic
__________
Advertisement
ABSTRACT
Background: In recent years, stem cell therapy has become a very promising and advanced scientific research topic. With advanced technology in tissue engineering, the development of this approach has evolved with great expectations.
Methods: This article is focused on the discovery of stem cells and their potential application in dentofacial orthodontic treatment. For craniofacial deformities, stem cell-based therapy has been applied as a part of a tissue engineering approach to regenerate bone and tissues to reconstruct the deformities. With a limitation of tissue defects, several stem cells could be great candidates for the treatment.
Conclusions: Stem cell-based therapy could be applied for TMJ regeneration with great potential for the development of scaffold regenerative materials. Current evidence demonstrates the potential of stem cellbased therapy for regenerate cementum, collagen and alveolar bone for the benefit of accelerated tooth movement, increased envelope of discrepancy and improved posttreatment stability.
Practical implications: However, there is a need for more in vivo and clinical trials for stem cell-based therapy to be used as a standard treatment.
Keywords: Stem cells, dentofacial, orthodontic, tissue engineering
––––––––––
Dentofacial orthodontic treatment involves treatment of dental malocclusion, dentofacial deformities and developmental anomaly. Orthodontic problems can affect several oral functions such as chewing, biting, swallowing and speaking and create abnormal habits such as tongue thrust and mouth breathing. [1] On several occasions, the problems are coincident with several developmental deformities and impact dentofacial aesthetics, psychosocial self-confidence and quality of life. [2–5] The worldwide prevalence of malocclusion is 56% without difference in sex, with varying severity in different parts of the world. [6] The prevalence of malocclusion was found to be higher and more severe in individuals with intellectual disabilities. [7] The prevalence of craniofacial anomalies and jaw deformities is less frequent compared to dental malocclusion, but the treatment is more challenging and needs multi- and interdisciplinary approaches. [8] Many approaches to these conditions involve regenerative medicine and stem cell therapy. This review article describes the applications of stem cells in the treatment of dentofacial orthodontic treatment.
Stem cells are undifferentiated cells of a multicellular organism that can differentiate into various types of cells under suitable conditions and have the ability of self-renewal. [9,10] Stem cells exist in embryonic, fetal and adult (somatic) stem cells. Developmental potency is very high in embryonic stem cells and is reduced with each step during the development. Stem cells can be classified in the following ways. [11]
Totipotent stem cells are able to proliferate and differentiate into cells of the whole organism. They have the highest differentiation potential for the cells to form both embryo and extraembryonic structures. Pluripotent stem cells (PSCs) form cells of all germ layers but not embryonic structures. The pluripotency starts from completely pluripotent cells and ends on representatives with less potency as multi-, oligo- or unipotent cells. PSCs can be derived from embryonic or fetal stem cells; however, in certain conditions, it could be derived from adult cells via the introduction of specific genes. [12] Multipotent stem cells have a narrower spectrum of differentiation than PSCs, but they can be driven to differentiate into specific cell lineages. These cells can become oligopotent cells and later differentiate into unipotent cells. Oligopotent stem cells can differentiate to several cell types while unipotent stem cells have limited differentiation capabilities and a unique capability to divide themselves continuously (FIGURE 1)
Somatic or adult stem cells are undifferentiated and are located among differentiated cells in the whole organism during development. These cells have limited ranges of differentiation and their functions are to replace the dying cells and promote regeneration, healing and growth of tissues. The stem cells derived from somatic stem cells have limited differentiation potential and tend to be unipotent stem cells and differentiate to a specific type of tissue such as skin, nerve or bone marrow (FIGURE 2). Induced pluripotent stem cells (iPSCs) are the somatic cells that achieve reverse pluripotency by forcing the expression of octamer-binding transcription factor (Oct4), sex-determining region Y (SOX2), Krüppel-like factor 4 (KLF4) and Myc genes encoding transcriptional factor. These processes convert somatic cells into pluripotent stem cells. [12]
The application of stem cells for dentofacial orthodontic treatment emphasized the regenerative potential aspect of stem cells. Several stem cells such as mesenchymal stem cells have been used in combination with grafting material for regenerative tissue engineering in several treatments such as cleft lip/palate augmentation, distraction osteogenesis, rapid palatal expansion and temporomandibular disorders. [13] Many procedures involve bone grafting to enhance the posttreatment stability and provide a scaffold for regenerative cells and new vascularity in the surgical or treatment area. Until now, adult stem cells from postnatal tissues have great potentials for clinical application due to several restrictions on embryonic stem cells including legal issues. Adult stem cells can be isolated from several tissues including the gastrointestinal tract, [14] skeletal muscle, [15] central nervous system, [16] adipose tissue [17] and neural crest derived tissues such as dental/periodontal tissues. [18,19] The adult bone marrow shelters various stem cells including hematopoietic (HSCs) [20] and mesenchymal stem cells (MSCs). [21] The process of stem cells-based therapy includes isolation, selection, testing and delivery of the stem cells to the surgical sites with a bioresorbable carrier or injection as shown in FIGURE 3.
Currently in the United States, the only stem cell-based products approved by the U.S. Food and Drug Administration (FDA) are hematopoietic progenitor cells (HPC) derived from cord blood. [22] However, several cell-based therapies have been approved by the FDA such as autologous CAR-positive viable T cells (Breyanzi, Kymriah, Tecartus and Yescarta) for treatment of B-cell lymphoma, autologous fibroblast intradermal injection (laViv) for treatment of nasolabial fold wrinkles, autologous cultured chondrocytes on porcine collagen membrane (Maci) for regeneration of knee cartilage defects and autologous CD54+ cells activated with PAP GM-CSF (Provenge) for treatment of certain types of prostate cancers. The cell-based therapy for intraoral use is Gintuit, the allogeneic cultured human keratinocytes and dermal fibroblasts in bovine Type I collagen for the treatment of mucogingival conditions such as gaining gingival keratinized tissue. [22] These cell-based therapies will provide a navigation for the development of stem cells-based therapy in the future.
Application in Treatment of Dentofacial/Craniofacial Deformities
These conditions encompass many different defective developmental conditions that cause the malformation of complete structures of the face and head. The most common conditions include cleft lip/palate (CLP) and craniosynostosis syndromes. These conditions require multi- and interdisciplinary treatment approaches that involve pediatricians, genetic physicians, geneticists/genetic counselors, plastic/craniofacial surgeons, orthodontists, pediatric dentists, prosthodontists, speech therapists, nurses, psychologists and social workers.
CLP is one of the most prevalent congenital craniofacial deformities. CLP occurs in approximately 1 per 940 births, [23] and 80% of the orofacial cleft are nonsyndromic and of multifactorial genetic and environmental origin. Craniosynostosis syndromes occur when one or more of the sutures in a baby’s skull closes too early. Children who have this condition might have an abnormal skull shape, forehead shape and asymmetrical eyes and/or ears. This condition occurs in approximately 1 per 2,000 births. Many cases of these conditions are of syndromic involvement while some cases are nonsyndromic.
The treatment of these craniofacial deformities involves reconstruction of the craniofacial defects including autogenous bone grafts, allogeneic material and prosthetic compounds such as metals and polymers. [24–26] Distraction osteogenesis has been widely applied in orthopedic surgery for correction in the treatment of several craniofacial deformities. [27] While increasingly utilized as endogenous bone tissue engineering, distraction osteogenesis could involve postoperative complications such as infection, scarring device failure and nonunion healing in up to 35% of cases. [28,29] The combination of stem cells with bone grafting for craniofacial reconstruction may alleviate these limitations due to its potential for regeneration for the tissues. The need for biocompatible scaffolds for the cells is under investigation due to the size of deformities such as palatal fissures. [30] Another concern is the number of stem cells for a large defect such as alveolar or palatal cleft. The bone marrow MSCs have been used in animal models, such as the dog model, and have demonstrated promising outcomes. [31,32] Bone marrow MSCs have been evaluated in a case report using a patient-specific, 3D printed bioresorbable polycaprolactone scaffold with autogenous bone marrow stromal cells collected from the iliac crest. The report showed 45% defect regeneration six months after transplantation, with a 75% bone mineral density compared to the surrounding bone. [33] Adipose-derived MSCs are another good candidate for stem cell-based therapy for CLP reconstruction due to their availability and easy handling. Stem cells from human exfoliated deciduous teeth are also good candidates for CLP reconstruction because they are less invasive to obtain and have higher accessibility; however, the number of stem cells could be a concern. Animal studies showed that these stem cells have the ability to repair the cleft site effectively and could be a good alternative for bone regeneration. [34–36] A recent elegant study from the University of Southern California reported the approach using a combination of biodegradable grafting material with MSCs to reverse craniosynostosis phenotypes and sustain calvarial bones and suture homeostasis of Twist1+/– mice. [37]
A human-based report discussed how stem cell-based therapy using stem cells and blood from an umbilical cord and placenta injection into the surgical sites was used during a rhinocheiloplasty procedure. All CLP patients were followed up for two years, and the outcome showed a smaller alveolar cleft and improved maxillary alignment; however, there was no evidence of osseous development. [38] A clinical trial evaluated mandibular regeneration using bone-derived MSCs for a patient with severe posterior mandibular ridge atrophy. The MSCs and biphasic calcium phosphate granules were used as scaffolds and were inserted subperiosteally onto the resorbed alveolar ridge. The results were assessed 12 months after the procedure; the bone augmentation of the posterior mandibular was successful for all patients. [39] A randomized controlled feasibility trial was performed to investigate the treatment of jaw bone defects using a mixture of CD90+ MSCs and CD14+ monocytes/macrophages and mononuclear cells from bone marrow. The treatment with MSCs accelerated alveolar bone regeneration and reduced the need for secondary bone grafting compared to conventional treatment. [40] The same group of authors further studied the potential of the mixture of CD90+ MSC cells and CD14+ monocyte/macrophages in maxillary sinus bone regeneration and found greater regenerative effects in these cells. [41] A study reported how autologous MSCs that were expanded in the laboratory were injected back into the patients’ mandibular surgical sites during the consolidation phase after distraction osteogenesis surgery that demonstrated favorable treatment outcomes. [42] Another study showed that grafting a combination of autologous deciduous dental pulp stem cells (DDPSC) and a hydroxyapatite-collagen sponge in alveolar bone defects in a group of CLP patients revealed satisfactory bone healing without significant complication after a six-month follow-up. [43]
Application in Treatment of Temporomandibular Disorders
Temporomandibular disorders (TMD) manifest their symptoms as pain, myalgia, headaches and structural destruction, collectively known as degenerative joint disease. [44] The prevalence of TMD in the U.S. is about 5%. [45] The temporomandibular joint (TMJ) comprises both osseous and cartilaginous structures and, like other synovial joints, is also prone to rheumatoid arthritis, injuries and congenital anomalies. [44] The severe form of TMD necessitates surgical replacement of the TMJ. [46] The complications of a surgical replacement of the TMJ include infection, implant wear, dislocation, donor site limitation and morbidity. [47] The application of stem cells for the treatment of TMJ replacement, including the delivery of stem cells in the existing defective TMJ structure, is used to promote tissue regeneration, [48–53] to introduce stem cells growth factors and biomolecules into the degenerative sites [54–57] and to incorporate stem cells with injectable polymers to form a scaffold with the cells. [58–60] The first human case reported was performed by injecting in vitro expanded autologous MSC cells from nasal septum into the patient’s degenerative TMJ by arthrocentesis. After six months, computed tomography images showed new cortical bone formation and partial repair of condylar and temporal bones. [61]
Application in Orthodontic Treatment Rapid Maxillary Expansion
Rapid maxillary expansion is an approach used to correct the constricted maxilla in certain patients. The action on the maxilla is similar to distraction osteogenesis either with or without surgical interventions. A preclinical study in rats showed that local injection of MSCs labeled with green fluorescent dye into an intermaxillary suture after activation of an expansion screw resulted in increased new bone formation in the suture by increasing the number of osteoclasts and new blood vessels compared to the control group. [62] In turn, the cells isolated from midpalatal sutures of mice could exhibit MSC markers, CD73, CD90, CD105 and Sca-1 after exposure to cyclic tensile force for two hours. [63] This implicates that the stem cell-based therapeutic approach could potentially benefit the rapid maxillary expansion and may help the posttreatment stability for bone regeneration after the expansion.
Surgically Facilitated Orthodontic Therapy
In 1994, Proffit and Ackerman first highlighted the importance of “the envelope of discrepancy” and how it portrays the range limitations of the maxillary and mandibular teeth during orthodontic treatment (inner envelope), orthodontic treatment combined with growth modification (middle envelope) and orthognathic surgery (outer envelope). [64] If the movement violates beyond the envelope of discrepancy, the dental and periodontal health of the patient may be compromised. With a shallow osteotomy, with shallow perforations or cuts made on the cortical alveolar bone only, the trabecular bone is left intact; with bone grafting, the envelope of discrepancy could be expanded for the orthodontic treatment and the rate of tooth movement could be accelerated. [65] As stated previously, MSCs could be used in combination with grafting materials to enhance bone regeneration as well as trophic mediator secretion to promote tissue regeneration around the tooth after movement. In addition to the rate of tooth movement being accelerated, this implicates the increased stability after surgically facilitated orthodontic therapy as well. [66]
Regeneration of Periodontal Tissue
Gingival recession or bony dehiscence could be unwanted consequences after orthodontic treatment. Interdental papilla recession after alignment of the crowded teeth is a major posttreatment concern. The solution to improve the “black triangle” is to remove the enamel thickness to squeeze the soft tissue between the teeth. This approach has limitations due to the thickness of enamel on the tooth, and it could harm the intact structure of enamel if the interdental papilla loss is excessive or the thickness of the enamel is limited. If periodontal ligament derived stem cells (PDSCs) could be used to regenerate cementum or periodontal bone, the alternative approach to gain the interdental papilla could be used. Several studies evaluated the potential of human PDSCs to induce cementum regeneration by transplanting PDSCs into athymic rat models. Human PDSCs demonstrated their capability to regenerate cementum, [67] bone and collagen fibers. [68,69]
Conclusion
The current literature revealed potential applications of stem cells in tissue engineering therapy for dentofacial orthodontic treatment. These stem cellbased therapies could be stem cells alone as cells and trophic factors for regeneration or in combination with regenerative scaffolds in the defect of the deformities. In addition, stem cell-based therapy could improve the treatment outcomes and duration as well as posttreatment stability. However, most of the evidence has shown in vitro and stem cell-based therapy to be expensive. In addition, the stem cell niche will be an important factor to consider when delivering stem cellbased therapies. More in vivo or clinical trials are required to assess the possibility of these innovative interventions.
__________
ACKNOWLEDGMENT This work was supported by the University of Illinois Chicago, Brodie Craniofacial Endowment fund and Biomedical Research Awards from the American Association of Orthodontists Foundation and DE024531, the National Institute of Dental and Craniofacial Research, National Institute of Health.
REFERENCES
1. Grippaudo C, Paolantonio EG, Antonini G, et al. Association between oral habits, mouth breathing and malocclusion. Acta Otorhinolaryngol Ital 2016 Oct;36(5):386–394. doi: 10.14639/0392-100X-770.
2. Dos Santos PR, Meneghim MC, Ambrosano GM, Filho MV, Vedovello SA. Influence of quality of life, self-perception and self-esteem on orthodontic treatment need. Am J Orthod Dentofacial Orthop 2017 Jan;151(1):143–147. doi: 10.1016/j.ajodo.2016.06.028.
3. Kiyak HA. Does orthodontic treatment affect patients’ quality of life? J Dent Educ 2008 Aug;72(8):886–94.
4. Silvola AS, Varimo M, Tolvanen M, et al. Dental esthetics and quality of life in adults with severe malocclusion before and after treatment. Angle Orthod 2014 Jul;84(4):594–9. doi: 10.2319/060213-417.1. Epub 2013 Dec 5.
5. Dalle H, Vedovello SAS, Degan VV, et al. Malocclusion, facial and psychological predictors of quality of life in adolescents. Community Dent Health 2019 Nov 28;36(4):298–302. doi: 10.1922/CDH_4633Dalle05.
6. Lombardo G, Vena F, Negri P, et al. Worldwide prevalence of malocclusion in the different stages of dentition: A systematic review and meta-analysis. Eur J Paediatr Dent 2020 Jun;21(2):115–122. doi: 10.23804/ejpd.2020.21.02.05.
7. Cabrita JP, Bizarra MF, Graca SR. Prevalence of malocclusion in individuals with and without intellectual disability: A comparative study. Spec Care Dentist 2017 Jul;37(4):181–186. doi: 10.1111/scd.12224. Epub 2017 Jun 9.
8. Salzmann JA. Editorial: Seriously handicapping orthodontic conditions. Am J Orthod 1976 Sep;70(3):329–30. doi: 10.1016/0002-9416(76)90340-7.
9. Atala AL, et al. Handbook of Stem Cells. 2nd ed. San Diego: Academic Press; 2013.
10. Parker GC, Anastassova-Kristeva M, Broxmeyer HE, et al. Stem cells: Shibboleths of development. Stem Cells Dev 2004 Dec;13(6):579–84. doi: 10.1089/scd.2004.13.579.
11. Zakrzewski W, Dobrzynski M, Szymonowicz M, Rybak Z. Stem cells: Past, present and future. Stem Cell Res Ther 2019 Feb 26;10(1):68. doi: 10.1186/s13287-019-1165-5.
12. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006 Aug 25;126(4):663–76. doi: 10.1016/j.cell.2006.07.024. Epub 2006 Aug 10.
13. Safari S, Mahdian A, Motamedian SR. Applications of stem cells in orthodontics and dentofacial orthopedics: Current trends and future perspectives. World J Stem Cells 2018 Jun 26;10(6):66–77. doi: 10.4252/wjsc.v10.i6.66.
14. Slack JM. Stem cells in epithelial tissues. Science 2000 Feb 25;287(5457):1431–3. doi: 10.1126/ science.287.5457.1431.
15. Charge SB, Rudnicki MA. Cellular and molecular regulation of muscle regeneration. Physiol Rev 2004 Jan;84(1):209–38. doi: 10.1152/physrev.00019.2003.
16. Daniela F, Vescovi AL, Bottai D. The stem cells as a potential treatment for neurodegeneration. Methods Mol Biol 2007;399:199–213. doi: 10.1007/978-1-59745-504-6_14.
17. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002 Dec;13(12):4279–95. doi: 10.1091/mbc.e02-02-0105.
18. Mitsiadis TA, Feki A, Papaccio G, Caton J. Dental pulp stem cells, niches and notch signaling in tooth injury. Adv Dent Res 2011 Jul;23(3):275–9. doi: 10.1177/0022034511405386.
19. Tomokiyo A, Wada N, Maeda H. Periodontal ligament stem cells: Regenerative potency in periodontium. Stem Cells Dev 2019 Aug 1;28(15):974–985. doi: 10.1089/ scd.2019.0031.
20. Spangrude GJ, Smith L, Uchida N, et al. Mouse hematopoietic stem cells. Blood 1991 Sep 15;78(6):1395– 402.
21. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997 Apr 4;276(5309):71–4. doi: 10.1126/science.276.5309.71.
22. U.S. Food and Drug Administration. Approved cellular and gene therapy products. March 02, 2021 ed. www.fda. gov/vaccines-blood-biologics/cellular-gene-therapy-products. Accessed March 12, 2021.
23. Parker SE, Mai CT, Canfield MA, et al. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol 2010 Dec;88(12):1008–16. doi: 10.1002/ bdra.20735. Epub 2010 Sep 28.
24. Rah DK. Art of replacing craniofacial bone defects. Yonsei Med J 2000 Dec;41(6):756–65. doi: 10.3349/ ymj.2000.41.6.756.
25. Bruens ML, Pieterman H, de Wijn JR, Vaandrager JM. Porous polymethylmethacrylate as bone substitute in the craniofacial area. J Craniofac Surg 2003 Jan;14(1):63–8. doi: 10.1097/00001665-200301000-00011.
26. Shenaq SM. Reconstruction of complex cranial and craniofacial defects utilizing iliac crest-internal oblique microsurgical free flap. Microsurgery 1988;9(2):154–8. doi: 10.1002/micr.1920090218.
27. McCarthy JG, Stelnicki EJ, Mehrara BJ, Longaker MT. Distraction osteogenesis of the craniofacial skeleton. Plast Reconstr Surg 2001 Jun;107(7):1812–27. doi: 10.1097/00006534-200106000-00029.
28. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH. Lengthening the human mandible by gradual distraction. Plast Reconstr Surg 1992 Jan;89(1):1–8; discussion 9–10.
29. Mofid MM, Manson PN, Robertson BC, et al. Craniofacial distraction osteogenesis: A review of 3278 cases. Plast Reconstr Surg 2001 Oct;108(5):1103–14; discussion 1115- 7. doi: 10.1097/00006534-200110000-00001.
30. Nyberg EL, Farris AL, Hung BP, et al. 3D-printing technologies for craniofacial rehabilitation, reconstruction and regeneration. Ann Biomed Eng 2017 Jan;45(1):45–57. doi: 10.1007/s10439-016-1668-5. Epub 2016 Jun 13.
31. Yoshioka M, Tanimoto K, Tanne Y, et al. Bone regeneration in artificial jaw cleft by use of carbonated hydroxyapatite particles and mesenchymal stem cells derived from iliac bone. Int J Dent 2012;2012:352510. doi: 10.1155/2012/352510. Epub 2012 Mar 26.
32. Tanimoto K, Sumi K, Yoshioka M, et al. Experimental tooth movement into new bone area regenerated by use of bone marrow-derived mesenchymal stem cells. Cleft Palate Craniofac J 2015 Jul;52(4):386–94. doi: 10.1597/12-232. Epub 2013 Jun 19.
33. Ahn G, Lee JS, Yun WS, Shim JH, Lee UL. Cleft alveolus reconstruction using a three-dimensional printed bioresorbable scaffold with human bone marrow cells. J Craniofac Surg 2018 Oct;29(7):1880–1883. doi: 10.1097/ SCS.0000000000004747.
34. Pourebrahim N, Hashemibeni B, Shahnaseri S, et al. A comparison of tissue-engineered bone from adipose-derived stem cell with autogenous bone repair in maxillary alveolar cleft model in dogs. Int J Oral Maxillofac Surg 2013 May;42(5):562–8. doi: 10.1016/j.ijom.2012.10.012. Epub 2012 Dec 7.
35. Lee JM, Kim HY, Park JS, et al. Developing palatal bone using human mesenchymal stem cell and stem cells from exfoliated deciduous teeth cell sheets. J Tissue Eng Regen Med 2019 Feb;13(2):319–327. doi: 10.1002/term.2811. Epub 2019 Jan 30.
36. Nakajima K, Kunimatsu R, Ando K, et al. Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells. Biochem Biophys Res Commun 2018 Mar 11;497(3):876–882. doi: 10.1016/j.bbrc.2018.02.156.
37. Yu M, Ma L, Yuan Y, et al. Cranial suture regeneration mitigates skull and neurocognitive defects in craniosynostosis. Cell 2021 Jan 7;184(1):243–256.e18. doi: 10.1016/j. cell.2020.11.037.
38. Mazzetti MPV, Alonso N, Brock RS, et al. Importance of stem cell transplantation in cleft lip and palate surgical treatment protocol. J Craniofac Surg 2018 Sep;29(6):1445– 1451. doi: 10.1097/SCS.0000000000004766.
39. Gjerde C, Mustafa K, Hellem S, et al. Cell therapy induced regeneration of severely atrophied mandibular bone in a clinical trial. Stem Cell Res Ther 2018;9(1):213. doi. org/10.1186/s13287-018-0951-9.
40. Kaigler D, Pagni G, Park CH, et al. Stem cell therapy for craniofacial bone regeneration: A randomized, controlled feasibility trial. Cell Transplant 2013;22(5):767–77. doi: 10.3727/096368912X652968.
41. Kaigler D, Avila-Ortiz G, Travan S, et al. Bone engineering of maxillary sinus bone deficiencies using enriched CD90+ stem cell therapy: A randomized clinical trial. J Bone Miner Res 2015 Jul;30(7):1206–16. doi: 10.1002/jbmr.2464.
42. Lim HJ, Lee EM, Kim WK, et al. Application of autologous human bone marrow-derived mesenchymal stem cells in distraction osteogenesis for the treatment of bilateral mandibular hypoplasia. J Craniofac Surg 2018 Sep;29(6):1629–1632. doi: 10.1097/ SCS.0000000000004614.
43. Tanikawa DYS, Pinheiro CCG, Almeida MCA, et al. Deciduous dental pulp stem cells for maxillary alveolar reconstruction in cleft lip and palate patients. Stem Cells Int 2020 Mar 12;2020:6234167. doi: 10.1155/2020/6234167. eCollection 2020.
44. Okeson JP. Evolution of occlusion and temporomandibular disorder in orthodontics: Past, present and future. Am J Orthod Dentofacial Orthop 2015 May;147(5 Suppl):S216–23. doi: 10.1016/j.ajodo.2015.02.007.
45. Lipton JA, Ship JA, Larach-Robinson D. Estimated prevalence and distribution of reported orofacial pain in the United States. J Am Dent Assoc 1993 Oct;124(10):115–21. doi: 10.14219/jada.archive.1993.0200.
46. Laskin DM, Renapurkar SK. Current Controversies in the Management of Temporomandibular Disorders. Oral Maxillofac Surg Clin North Am 2018 Aug;30(3):xiii. doi: 10.1016/j.coms.2018.05.005. Epub 2018 Jul 5.
47. Jacobs JJ, Gilbert JL, Urban RM. Corrosion of metal orthopaedic implants. J Bone Joint Surg Am 1998 Feb;80(2):268–82. doi: 10.2106/00004623-199802000- 00015.
48. Brady MA, Sivananthan S, Mudera V, et al. The primordium of a biological joint replacement: Coupling of two stem cell pathways in biphasic ultrarapid compressed gel niches. J Craniomaxillofac Surg 2011 Jul;39(5):380–6. doi: 10.1016/j.jcms.2010.07.002. Epub 2010 Aug 31.
49. Chen K, Man C, Zhang B, Hu J, Zhu SS. Effect of in vitro chondrogenic differentiation of autologous mesenchymal stem cells on cartilage and subchondral cancellous bone repair in osteoarthritis of temporomandibular joint. Int J Oral Maxillofac Surg 2013 Feb;42(2):240–8. doi: 10.1016/j. ijom.2012.05.030. Epub 2012 Jul 2.
50. Yoshimura H, Muneta T, Nimura A, et al. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue and muscle. Cell Tissue Res 2007 Mar;327(3):449–62. doi: 10.1007/s00441-006-0308-z. Epub 2006 Oct 13.
51. Koga H, Muneta T, Nagase T, et al. Comparison of mesenchymal tissues-derived stem cells for in vivo chondrogenesis: Suitable conditions for cell therapy of cartilage defects in rabbit. Cell Tissue Res 2008 Aug;333(2):207–15. doi: 10.1007/s00441-008-0633-5. Epub 2008 Jun 17.
52. Wu Y, Gong Z, Li J, et al. The pilot study of fibrin with temporomandibular joint derived synovial stem cells in repairing TMJ disc perforation. Biomed Res Int 2014;2014:454021. doi: 10.1155/2014/454021. Epub 2014 Apr 15.
53. Okano T, Yamada N, Sakai H, Sakurai Y. A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide). J Biomed Mater Res 1993 Oct;27(10):1243–51. doi: 10.1002/ jbm.820271005.
54. MacFarlane RJ, Graham SM, Davies PS, et al. Antiinflammatory role and immunomodulation of mesenchymal stem cells in systemic joint diseases: Potential for treatment. Expert Opin Ther Targets 2013 Mar;17(3):243–54. doi: 10.1517/14728222.2013.746954. Epub 2013 Jan 8.
55. Zhang J, Guo F, Mi J, Zhang Z. Periodontal ligament mesenchymal stromal cells increase proliferation and glycosaminoglycans formation of temporomandibular joint derived fibrochondrocytes. Biomed Res Int 2014;2014:410167. doi: 10.1155/2014/410167. Epub 2014 Nov 10.
56. Kato T, Miyaki S, Ishitobi H, et al. Exosomes from IL-1beta stimulated synovial fibroblasts induce osteoarthritic changes in articular chondrocytes. Arthritis Res Ther 2014 Aug 4;16(4):R163. doi: 10.1186/ar4679.
57. Wang Y, Yu D, Liu Z, et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther 2017 Aug 14;8(1):189. doi: 10.1186/s13287-017-0632-0.
58. Lim EH, Sardinha JP, Myers S. Nanotechnology biomimetic cartilage regenerative scaffolds. Arch Plast Surg 2014 May;41(3):231–40. doi: 10.5999/aps.2014.41.3.231. Epub 2014 May 12.
59. Liu M, Zeng X, Ma C, et al. Injectable hydrogels for cartilage and bone tissue engineering. Bone Res 2017 May 30;5:17014. doi: 10.1038/boneres.2017.14. eCollection 2017.
60. Wang LS, Du C, Toh WS, et al. Modulation of chondrocyte functions and stiffness-dependent cartilage repair using an injectable enzymatically crosslinked hydrogel with tunable mechanical properties. Biomaterials 2014 Feb;35(7):2207– 17. doi: 10.1016/j.biomaterials.2013.11.070. Epub 2013 Dec 12.
61. de Souza Tesch R, Takamori ER, Menezes K, et al. Temporomandibular joint regeneration: Proposal of a novel treatment for condylar resorption after orthognathic surgery using transplantation of autologous nasal septum chondrocytes and the first human case report. Stem Cell Res Ther 2018;9(1):94. doi: 10.1186/s13287-018-0806-4.
62. Ekizer A, Yalvac ME, Uysal T, Sonmez MF, Sahin F. Bone marrow mesenchymal stem cells enhance bone formation in orthodontically expanded maxillae in rats. Angle Orthod 2015 May;85(3):394–9. doi: 10.2319/031114-177.1. Epub 2014 Jul 23.
63. Mojarrad S. Effect of Expansive Force on Mesenchymal Stem Cells Isolated From the Mid-Palatal Suture of Mice. University of Pennsylvania Scholarly Commons: University of Pennsylvania; 2018.
64. Proffit W, et al. Diagnosis and Treatment Planning in Orthodontics. In: Graber LW, Vig KW, Vanarsdall RL, Huang GJ, eds. Orthodontics: Current Principles and Techniques. St. Louis: Mosby; 1994:3–95.
65. Hoogeveen EJ, Jansma J, Ren Y. Surgically facilitated orthodontic treatment: A systematic review. Am J Orthod Dentofacial Orthop 2014 Apr;145(4 Suppl):S51–64. doi: 10.1016/j.ajodo.2013.11.019.
66. Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006 Aug 1;98(5):1076–84. doi: 10.1002/jcb.20886.
67. Yamato M, Okano T. Cell sheet engineering. Mater Today 2004 7(5)42–7. doi.org/10.1016/S1369- 7021(04)00234-2.
68. Grimm WD, Dannan A, Becher S, et al. The ability of human periodontium-derived stem cells to regenerate periodontal tissues: A preliminary in vivo investigation. Int J Periodontics Restorative Dent Nov–Dec 2011;31(6):e94–e101.
69. Seo BM, Miura M, Gronthos S, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 2004 Jul 10–16;364(9429):149–55. doi: 10.1016/S0140-6736(04)16627-0.
THE AUTHOR, Phimon Atsawasuwan, DDS, MSc, MSc, MS, PhD, can be reached at patsawas@uic.edu.
