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ABSTRACT: Multipotent postnatal stem cells can be isolated from human periodontal ligaments (PDLs) and have the potential for large-scale expansion, offering a reliable cell source for clinical use in periodontal regenerative therapies. However, the effects of aging on the mesenchymal stem cell (MSC) properties of these cells remain undefined. The aims of this study were to isolate and characterize the periodontal ligament stem cells (PDLSCs) derived from human impacted third molars of donors of different ages and to compare their pluripotential capacity and regenerative potential. PDL tissues were obtained from 90 surgically extracted third molars and divided into four groups according to the donor's age. For each group, the colony-forming ability, proliferative capacity, migratory potential, cell surface antigens, differentiation ability, alkaline phosphatase activity, and gene expression of the PDLSCs were contrastively evaluated and quantified for statistical analysis. The in vivo tissue regenerative potential of PDLSCs was assessed by an in vivo ectopic transplantation model. It was found that human PDLSCs were successfully isolated and characterized as MSCs in all 90 teeth. PDLSCs derived from donors of different ages were successfully differentiated under an osteogenic and adipogenic microenvironment. The proliferative and migratory potential and the differentiation capacity of PDLSCs decreased as age increased (p < 0.05). PDLSCs derived from donors whose age is 62.6 ± 6.8 have a statistically significant decrease in pluripotential capacity compared with those derived from relatively young donors (p < 0.01). There is no identified cementum and PDL-like tissue formation in vivo among the two aging groups. We conclude that human PDLSCs could be successfully isolated from PDL tissue derived from donors of different ages, but the age-related changes of the MSC properties should be taken into account whenever they are intended for use in research or cytotherapy.
Biomaterials 07/2012; 33(29):6974-86. · 7.40 Impact Factor
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ABSTRACT: Periodontitis is a globally prevalent inflammatory disease that causes the destruction of the tooth-supporting apparatus and potentially leads to tooth loss. Currently, the methods to reconstitute lost periodontal structures (i.e. alveolar bone, periodontal ligament, and root cementum) have relied on conventional mechanical, anti-infective modalities followed by a range of regenerative procedures such as guided tissue regeneration, the use of bone replacement grafts and exogenous growth factors (GFs), and recently developed tissue engineering technologies. However, all current or emerging paradigms have either been shown to have limited and variable outcomes or have yet to be developed for clinical use. To accelerate clinical translation, there is an ongoing need to develop therapeutics based on endogenous regenerative technology (ERT), which can stimulate latent self-repair mechanisms in patients and harness the host's innate capacity for regeneration. ERT in periodontics applies the patient's own regenerative 'tools', i.e. patient-derived GFs and fibrin scaffolds, sometimes in association with commercialized products (e.g. Emdogain and Bio-Oss), to create a material niche in an injured site where the progenitor/stem cells from neighboring tissues can be recruited for in situ periodontal regeneration. The choice of materials and the design of implantable devices influence therapeutic potential and the number and invasiveness of the associated clinical procedures. The interplay and optimization of each niche component involved in ERT are particularly important to comprehend how to make the desired cell response safe and effective for therapeutics. In this review, the emerging opportunities and challenges of ERT that avoid the ex vivo culture of autologous cells are addressed in the context of new approaches for engineering or regeneration of functional periodontal tissues by exploiting the use of platelet-rich products and its associated formulations as key endogenous resources for future clinical management of periodontal tissue defects.
Biomaterials 11/2010; 31(31):7892-927. · 7.40 Impact Factor
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ABSTRACT: Periodontitis, an almost ubiquitous disorder in the adult population, induces the breakdown of tooth-supporting apparatus which, unfortunately, has an extremely limited capacity for self-repair and regeneration. The recent discovery of progenitor/stem cells residing in the periodontium, however, raises the possibility of restoring damaged periodontal tissues by recruiting their latent regenerative potential. Within the reparative process, stem cell fates may be influenced by a number of signaling molecules, such as growth factors (GFs), that require robust control for safe and effective regeneration of functional tissues. Numerous GFs with the ability to promote the regeneration of periodontal tissues have been identified thus far, but their clinical use is often hindered by delivery problems. Regulation of cell activity within a complex in vivo milieu requires the incorporation of multifaceted release technologies that offer physiological levels of GFs, mimicking the natural wound healing cascade by using tools of tissue engineering and protein/gene delivery. This should not be limited to the provision of a single GF but should instead release multiple essential GFs at an optimized ratio in a specific spatiotemporal mode. This article summarizes current limitations and new opportunities related to release technology in periodontal regenerative medicine, highlighting the importance as well as challenges with respect to delivering multiple GFs in an orderly temporal and spatial sequence to mimic their natural expression patterns. Recent progress highlights the importance of releasing endogenous GFs and developing commercially available products that may facilitate clinical translation.
Journal of Controlled Release 10/2010; 149(2):92-110. · 5.73 Impact Factor
