| Periodontal tissue breakdown around natural teeth due to periodontitis, aworldwide medical concern and a leading cause for tooth loss, poses a criticalchallenge for regenerative dentistry. The restoration of tooth-supportingapparatus is an extremely complex process because of the involvement of theregeneration of three unique tissue types, namely cementum, periodontalligament (PDL), and alveolar bone, and the re-sestablishment of their intricatestructures. Stem cells are the most fascinating area of biology today and havebeen used clinically in the field of regenerative medicine to treat manydegradative diseases including periodontitis. Of note, various human and animalstudies have confirmed the presence of stem cells in dental tissues in and arounda tooth. This has opened new avenues that aim toward the use of stem cells inreconstructive dentistry for the treatment of periodontal disease. Before the identification stem cell populations in the PDL tissue, there ismounting evidence that PDL cells exhibit osteoblastic characteristics, becausethey are capable of producing mineral-like nodules, and express bone-associatedgenes, osteocalcin, osteopontin, bone sialoprotein, bone morphogenic proteins(BMP)-2and-4, and alkaline phosphatase (ALP). In2004, a pioneer studydemonstrated that PDL contains stem cells (generally termed PDL stem cells orPDLSCs) that have the potential to differentiate into cementoblast-like cells,adipocytes, and collagen-forming cells in vitro, and to generate newcementum/PDL-like compartments in vivo. In addition, they exhibit afibroblast-like morphology and express CD90, CD29, CD44, CD166, CD105,and CD13antigens that have also been identified as stromal precursors of thebone marrow. Interestingly, recent data suggest that PDLSCs could be isolatedfrom both healthy and inflamed PDL tissue; the inflamed PDLSCs retain theirregenerative potential for cementum and related PDL tissues, offering analternative source of mesenchymal stem cells (MSCs) for therapeutic use.Clearly, the use of PDLSCs involves less religious and ethical concerns becausethey are easily obtainable from medical waste, i.e., the extracted teeth fororthodontic, impaction, or irreversible periodontits reasons. Therefore, PDLSCsrepresent a unique population of MSCs that may facilitate translational researchand indeed, future clinical application.The ability to identify and manipulate human PDLSCs has been asignificant advancement in regenerative dentistry and has contributed to asignificant development in the progress toward predictable periodontalregeneration. One of the critical requirements for cell-based approach is thedelivery of ex vivo expanded progenitor populations or the mobilization ofendogenous progenitor cells capable of proliferating and differentiating into the required tissues. The latter strategy unfortunately does not offer a universalregenerative solution because innate powers of regeneration may be restrictedby an age-related decline in progenitor populations that can be moblized or bythe intrinsically low regenerative potential of certain tissues. In these cases, orwhere the original tissue has been completely destroyed, biomaterialsinterventions that include an external source of cells may be required. Today, themethods to isolate, purify, and characterize multipotent stem cells in human PDLhave been delineated, and large-scale expansion of stem cells to cater for theneed for clinical quantity without using animal sera as nutritional supplements isbecoming possible. Nevertheless, considering the complexity of the PDLattachment apparatus and the heterogeneity of its cell populations, thestandardization of the appropriate cell populations necessary for completeregeneration remains one of the key factors in implementing optimal approachesto periodontal regeneration. Although there have already feasible studies that usePDLSCs in periodontal wound healing and regeneration, the influences of agingon the MSC properties of PDLSCs remain unidentified, which, however, mayhave significant effects on final clinical outcomes because tissue regenerativepotential may be negatively regulated by aging. In fact, age-related effects ofstem cells have been notified in different tissues, but little is known aboutwhether PDLSCs exhibit different features, when extracted from young andaged donors. The aims of this study were to isolate and characterize the PDLSCsderived from human impacted third molars of different aged donors, and tocompare their pluripotential capacity and regenerative potential, thus providingdata that may help for case or cell source selection in future clinical trials onstem cell-based periodontal therapeutics. Objectives: Multipotent postnatal stem cells could be isolated from humanperiodontal ligaments and promise to large-scare expansion, offering a reliablecell source for clinical use in periodontal regeneration. However, the effects ofaging on their mesenchymal stem cell (MSC) properties remain undefined. Theaims of this study were to isolate and characterize the PDLSCs derived fromhuman impacted third molars of different aged donors, and to compare theirpluripotential capacity and regenerative potential.Materials and Methods: PDL tissues were obtained from90surgicallyextracted third molars and divided into four groups according to the donor’s age.A group (16-30years), B group (31-40years), C group (41-55years), and Dgroup (55-75years) For each group, the colony-forming ability, proliferativecapacity, the cell surface antigens, differentiation ability of PDLSCs werecontrastively evaluated and quantified for statistical analysis. Regenerativepotential was assessed by an in vivo ectopic transplantation model.Results: Group information was: A group (age range22.3±7.7, male8,female7), B group (age range35.6±4.3, male7, female7), C group (age range48.2±6.1, male6, female6), and D group (age range62.6±6.8, male7, female6). Human PDLSCs were successfully isolated and characterized as MSCs in all90teeth. PDLSCs derived from different aged donors were successfullydifferentiated under osteogenic and adipogenic microenvironment. Theproliferative and migratory potential as well as the differentive capacity ofPDLSCs decreased along with increasing age (P<0.05). PDLSCs derived from donors whose age is62.6±6.8have a statistically significant decrease inpluripotential capacity as compared to those derived from relatively youngdonors (P<0.01). In vivo data have not been finalized.Conclusion: Human PDLSCs could be successfully isolated from PDL tissuederived from different aged donors, but age-related changes of the MSCproperties should be taken into account whenever they are intended to be usedfor investigations.Part2Case presentations: we provided three cases on the proposal “PeriodontalTissue Regeneration Using Periodontal Ligament Stem Cells: A RandomizedControlled Phase I/II Clinical Trial”. The purpose of this clinical trial is to bothclarify the efficiency of autologous periodontal ligament (PDL) stem cells in theforms of cell sheets to regenerate periodontal tissue in periodontitis patients withdeep intraosseous defects (>5mm) and to confirm the safety of using autologousstem cells in clinicial periodontal regenerative medicine. This is a single-centre,randomized, placebo-controlled study. This study has been approved by theethical committees of School of Stomatology, Fourth Military MedicalUniversity (2011-02) and is registered with ClinicalTrials.gov database(reference no. NCT01357785). The study will be conducted according to theDeclaration of Helsinki. |
PDF Full Text Request