Papers by Prof.Gianpaolo Papaccio
Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour ... more Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable. Noteworthy, SAOS2 and MCF7 cells induced in hASCs an upregulation of CD34 expression and stemness genes, including OCT3/4, Nanog, Sox2 and leptin, and a decrease in angiogenic factors, including CD31, PDGFα, PDGFRα, PDGFRβ and VEGF. SMAD and pSMAD2/3 increased only in hASCs alone. After 21 days of co-culture, hASCs differentiated both in adipocytes and endothelial cells. Moreover, co-injection of MCF7 cells with hASCs led to the formation of a highly vascularized tumour. Taken together our findings suggest that mesenchymal stem cells, under tumour cell induction, do not differentiate in vitro or facilitate the angiogenesis of the tumour in vivo, thus opening interesting new scenarios in the relationship between cancer and stem cells. These findings may also lead to greater caution, when managing autologous fat grafts in cancer patients.
Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunom... more Fusidic acid and sodium fusidate (fusidin) are antibiotics with low toxicity and powerful immunomodulatory activities in vitro and in vivo. In this study we have evaluated the effect of fusidin on the development of dinitrobenzenesulfonic acid (DNB)-induced colitis in rats that serves as a preclinical model of human inflammatory bowel disease (IBD). The data show that when administered orally at the dose of 80 (but not 40) mg/kg body wt under a " therapeutic " regimen soon after DNB application, fusidin significantly ameliorates clinical, histological, and seroimmunological signs of disease. These entailed a significant reduction in body weight loss, smaller increase in colon weights, milder macroscopic damage, and lower histological scores. In addition, when sacrificed at the end of the study, fusidin-treated rats had significantly lower blood levels of tumor necrosis factor and interferon-compared with untreated controls. The present findings concur with the beneficial actions of fusidin in a pilot study conducted in patients with Crohn's disease and warrant controlled studies in humans with IBD.
Interleukin (IL)-1b-treated rat islets of Langerhans were exposed in vitro either to the imidazol... more Interleukin (IL)-1b-treated rat islets of Langerhans were exposed in vitro either to the imidazoline compound, Efaroxan, or to the selective inducible nitric oxide synthase (iNOS) inhibitor, 1400W, in a medium containing a high concentration of glucose (16.7 mmol/L). Our data have evidenced the following: (i) addition of Efaroxan to islet cultures inhibited IL-1b activation of ICE (cysteine protease IL-1b converting enzyme) while addition of 1400W did not; (ii) Efaroxan completely inhibited IL-1b-induced suppression of insulin secretion and induction of iNOS mRNA transcripts, and, in addition, counteracted islet b-cell protein profile alterations, Bax-cytochrome c translocation, caspase activation, and apoptosis; (iii) 1400W inhibited IL-1b induction of iNOS, but failed to completely counteract the other cytotoxic effects; (iv) the two compounds, moreover, exerted different effects on manganese superoxide dismutase (MnSOD), in fact, while Efaroxan inhibited the early stimulatory effect of IL-1b on MnSOD, 1400W did not. Thus, Efaroxan completely protected islet b cells from damage caused by IL-1b-induced toxicity, while compound 1400W only inhibited NO radical production without altering the cytokine's cytotoxicity. Our observations have evidenced that suppression of ICE activation is required to counteract IL-1b-mediated islet b cell toxicity, and that IL-1b-induced apoptosis is NO-independent and involves the cytochrome c-mitochondrial pathway.
IL-1b is an important mediator in the pathogenesis of type 1 diabetes both in vivo and in vitro a... more IL-1b is an important mediator in the pathogenesis of type 1 diabetes both in vivo and in vitro and it has been shown to induce islet b-cell apoptosis. Most of the IL-1b effects seem to be mediated by NF-kB transcription factor activation, but its role in the induction of islet b-cell apoptosis has not yet been clarified. Taking advantage of the protease inhibitor TPCK (N-tosyl-L-phenylalanine chloromethyl ketone), which specifically inhibits the nuclear transcription factor NF-kB activation, we studied the role of NF-kB in the rIL-1b treated rat pancreatic islets. Our results show that TPCK blocked rIL-1b-mediated early increase of MnSOD activity and b-cell defence/repair protein expression, suggesting a protective role for NF-kB at the beginning of IL-1b treatment; but, in a second phase, NF-kB induces a sustained decrease of specific b-cell proteins like insulin, GLUT-2 and PDX-1 with a concomitant increase of aspecific proteins and iNOS transcription. The appearance of iNOS expression correlates with increased levels of nitrite þ nitrate levels and appearance of mitochondrial damage detected either at morphological and biochemical level. After 36 h of IL-1b treatment islet b-cells begin to undergo apoptosis. Since IL-1b induction of apoptosis is completely prevented by TCPK treatment, this finding underscores the central role of NF-kB in this process. Thus, our results clearly indicate that NF-kB regulates MnSOD genes expression and MnSOD activity, which protects islet b-cells by IL-1b damage. Furthemore, when the IL-1b stress impairs islet b-cell function, NF-kB activation regulates the entrance of islet b-cell into the cell death program.
Stem cells, derived from human adult dental pulp of healthy subjects 30–45 years of age, were cul... more Stem cells, derived from human adult dental pulp of healthy subjects 30–45 years of age, were cultured, and cells were selected using a FACSorter. A new c-kit + /CD34 + /CD45 − cell population of stromal bone producing cells (SBP/DPSCs) was selected, expanded, and cultured. These SBP/DPSCs are highly clo-nogenic and, in culture, differentiate into osteoblast precursors (CD44 + /RUNX-2 +), still capable of self-renewing, and then in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue, which is markedly positive for several bone antibodies. This tissue constitute an ideal source of osteoblasts and min-eralized tissue for bone regeneration. In fact, after in vivo transplantation into immunocompromised rats, LAB formed lamellar bone-containing osteocytes. Introduction: Recently it has been reported that human dental pulp stem cells (DPSCs) are detectable, in humans, only up to the age of 30 years and that they are able to produce in vitro only sporadic calcified nodules and to form, after transplantation in vivo, a mineralized tissue. Materials and Methods: Stem cells, derived from human adult dental pulp of healthy subjects 30–45 years of age, were cultured, and cells were selected using a FACSorter. Light microscope, histochemistry, immuno-fluorescence, and RT-PCR analyses were performed to study both stem and differentiating cells. Results and Conclusions: A new c-kit + /CD34 + /CD45 − cell population of stromal bone producing cells (SBP/ DPSCs) has been selected by FACSorting, expanded, and cultured. These SBP/DPSCs are highly clonogenic and, in culture, differentiate into osteoblast precursors (CD44 + /RUNX-2 +), still capable of self-renewing , and in osteoblasts, producing, in vitro, a living autologous fibrous bone (LAB) tissue. This new-formed tissue is markedly positive for several antibodies for bone, including osteonectin, bone sialopro-tein, osteocalcin, fibronectin, collagen III, and bone alkaline phosphatase (BALP). Cells producing LAB can be stored at −80°C for a long period of time and are an extraordinary source of osteoblasts and mineralized fibrous bone tissue. In this study, we also showed that, in aged humans, stem cells can be detected from their pulps. The produced LAB is a fibrous bone tissue resembling the human bone during mineraliza-tion, with an external layer formed by osteoblasts markedly positive for osteocalcin. This newly formed tissue constitute an ideal source of osteoblasts and mineralized tissue for bone regeneration. In fact, after in vivo transplantation into immunocompromised rats, LAB formed lamellar bone containing osteocytes.
Stem cells were obtained from deciduous dental pulp of healthy subjects, aged 6–10 years. This st... more Stem cells were obtained from deciduous dental pulp of healthy subjects, aged 6–10 years. This stem cell population was cultured, expanded, and specifically selected, detecting using a FACsorter, c-kit, CD34, and STRO-1 antigen expression. Then, c-kit þ / CD34 þ /STRO-1 þ cells were replaced in the culture medium added of 20% FBS, leading to osteoblast differentiation. In fact, these cells, after a week, showed a large positivity for CD44, osteocalcin, and RUNX-2 markers. To achieve an adipocytic differentiation, cells, after sorting, were challenged with dexamethason 10 À8 mM in the same culture medium. To obtain myotube fusion, sorted cells were co-cultured in ATCC medium with mouse myogenic C2C12 cells and, after a week, human stem cell nuclei were found to be able to fuse, forming myotubes. Differentiated osteoblasts, as assessed by a large positivity to several specific antibodies, after 30 days of culture and already in vitro, started to secrete an extracellular mineralized matrix, which, 2 weeks later, built a considerable number of 3D woven bone samples, which showed a strong positivity to alkaline phosphatase (ALP), alizarin red, calcein, other than to specific antibodies. These bone samples, after in vivo transplantation into immunosuppressed rats, were remodeled in a lamellar bone containing entrapped osteocytes. Therefore, this study provides strong evidence that human deciduous dental pulp is an approachable ''niche'' of stromal stem cells, and that it is an ideal source of osteoblasts, as well as of mineralized tissue, ready for bone regeneration, transplantation, and tissue-based clinical therapies.
It is not known whether cells derived from stem cells retain their differentiation and morpho-fun... more It is not known whether cells derived from stem cells retain their differentiation and morpho-functional properties after long-term cryopreservation. This information is of importance to evaluate their potential for long-term storage with a view to subsequent use in therapy. Here, we describe the morpho-functional properties of dental pulp stem cells (SBP-DPSCs), and of their differentiated osteoblasts, recovered after long-term cryopreservation. After storage for 2 years, we found that stem cells are still capable of differentiation, and that their differentiated cytotypes proliferate and produce woven bone tissue. In addition, cells still express all their respective surface antigens, confirming cellular integrity. In particular, SBP-DPSCs differentiated into pre-osteoblasts, showing diffuse positivity for ALP, BAP, RUNX-2, and calcein. Recovered osteoblasts expressed bone-specific markers and were easily recognizable ultrastructurally, with no alterations observed at this level. In addition, after in vivo transplantation, woven bone converted into a 3D lamellar bone type. Therefore, dental pulp stem cells and their osteoblast-derived cells can be long-term cryopreserved and may prove to be attractive for clinical applications.
During the 1st International Meeting on ''Stem Cell Applications in the Craniofacial Region'' pro... more During the 1st International Meeting on ''Stem Cell Applications in the Craniofacial Region'' promoted in Naples (Italy), invited researchers presented their work and the most innovative methods regarding stem cells (SCs) and their application to the craniofacial region of the human body. In addition, some researchers showed their case-reports on craniofacial reconstruction using either osteo-distraction or reconstruction surgical methods. The aim of this biannual meeting is to stimulate discussion, improve knowledge and promote scientific collaboration among basic and clinical scientists in the main topics of SC use in therapy. A summary of this meeting is given.
Non-hypercalcemic analogs of vitamin D 3 modulate the immune response through antigen-presenting ... more Non-hypercalcemic analogs of vitamin D 3 modulate the immune response through antigen-presenting cells (APCs) and activated T-cells. A large population-base case-control showed that vitamin D 3 intake significantly decreases the risk of type 1 diabetes development. The aim of this study was, therefore, to observe the in vivo effects of a vitamin D 3 analog administered to Bio Breeding (BB) rats. 1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D 3 (BXL-219, formerly Ro 26-2198) (BioXell, Milan, Italy) was administered in vivo to BB rats from days 42 to 110 of life at 0.2 mg/Kg BW. Control animals received only vehicle (olive oil, 4.8 ml/100 g BW). The animals of these two groups were subjected to insulin treatment as they became diabetic. Insulin (Humulin, 28.6 UI/day) was administered irrespective of diabetes occurrence to another group of rats for comparison. Blood glucose, insulin levels, glycosuria, degree of islet infiltration, and the expression of some antigens were observed. Results showed that the vitamin D 3 analog reduced diabetes incidence, although limitedly, in BB rats while administration of oral insulin increased diabetes incidence. In addition, the vitamin D 3 analog did not stimulate an enhancement in the expression of CD4 and CD25 in BB rats as it does in NOD mice, which may explain the failure of this as well as other antidiabetic treatments in the BB animal model of type 1 diabetes.
Pancreatic islets are commonly isolated for research and transplantation without taking into cons... more Pancreatic islets are commonly isolated for research and transplantation without taking into consideration that they undergo mechanical or chemical stress during this process. In order to counteract both types of injuries, the compound AEOL10150, a novel MnSOD mimic, was added during isolation of islet at concentrations ranging from 18 to 100 mM. Mechanical or chemical stress-related pro-apoptotic signals were then studied. We demonstrate that this MnSOD mimic diminishes the negative effects of mechanical stress by blocking insulin impairment, production of non-specific islet b-cell proteins, transcription of iNOS and FAS, activation of caspase-3 and-9 and, ultimately, apoptosis. Moreover, the effects of the MnSOD mimic on isolated islets were greatly influenced by dosage: the best dose able to fully counteract mechanical stress was found to be 100 mM; doses !150 mM were themselves highly toxic for islet cells. On the other hand, rIL-1b-induced chemical stress is rather complex, and there was no protection in this scenario. Therefore, contrarily to what has been previously reported, MnSOD mimic administration is only capable of counteracting mechanical stress, and not cytokine-induced cytotoxicity, and that this drug acts within a limited concentration range.
Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiati... more Stromal stem cells from human dental pulp (SBP-DPSCs) were used to study osteogenic differentiation in vitro and in vivo. We previously reported that SBP-DPSCs are multipotent stem cells able to differentiate into osteoblasts, which synthesize three-dimensional woven bone tissue chips in vitro. In this study, we followed the temporal expression pattern of specific markers in SBP-DPSCs and found that, when differentiating into osteoblasts, they express, besides osteocalcin, also flk-1 (VEGF-R2). In addition, 30% of them expressed specific antigens for endothelial cells, including CD54, von-Willebrand (domain 1 and 2), CD31 (PECAM-1) and angiotensin-converting enzyme. Interestingly, we found endotheliocytes forming vessel walls, observing that stem cells synergically differentiate into osteoblasts and endotheliocytes, and that flk-1 exerts a pivotal role in coupling osteoblast and endotheliocyte differentiation. When either SBP-DPSCs or bone chips obtained in vitro were transplanted into immunocompromised rats, they generated a tissue structure with an integral blood supply similar to that of human adult bone; in fact, a large number of HLA-1 þ vessels were observed either within the bone or surrounding it in a periosteal layer. This study provides direct evidence to suggest that osteogenesis and angiogenesis mediated by human SBP-DPSCs may be regulated by distinct mechanisms, leading to the organization of adult bone tissue after stem cell transplantion.
Background. Scaffold surface features are thought to be important regulators of stem cell perform... more Background. Scaffold surface features are thought to be important regulators of stem cell performance and endurance in tissue engineering applications, but details about these fundamental aspects of stem cell biology remain largely unclear. Methodology and Findings. In the present study, smooth clinical-grade lactide-coglyolic acid 85:15 (PLGA) scaffolds were carved as membranes and treated with NMP (N-metil-pyrrolidone) to create controlled subtractive pits or microcavities. Scanning electron and confocal microscopy revealed that the NMP-treated membranes contained: (i) large microcavities of 80– 120 mm in diameter and 40–100 mm in depth, which we termed primary; and (ii) smaller microcavities of 10–20 mm in diameter and 3–10 mm in depth located within the primary cavities, which we termed secondary. We asked whether a microcavity-rich scaffold had distinct bone-forming capabilities compared to a smooth one. To do so, mesenchymal stem cells derived from human dental pulp were seeded onto the two types of scaffold and monitored over time for cytoarchitectural characteristics, differentiation status and production of important factors, including bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF). We found that the microcavity-rich scaffold enhanced cell adhesion: the cells created intimate contact with secondary microcavities and were polarized. These cytological responses were not seen with the smooth-surface scaffold. Moreover, cells on the microcavity-rich scaffold released larger amounts of BMP-2 and VEGF into the culture medium and expressed higher alkaline phosphatase activity. When this type of scaffold was transplanted into rats, superior bone formation was elicited compared to cells seeded on the smooth scaffold. Conclusion. In conclusion, surface microcavities appear to support a more vigorous osteogenic response of stem cells and should be used in the design of therapeutic substrates to improve bone repair and bioengineering applications in the future.
In this study, we have observed dental pulp stem cells (SBP-DPSCs) performances on different scaf... more In this study, we have observed dental pulp stem cells (SBP-DPSCs) performances on different scaffolds, such as PLGA 85:15, hydroxyapatite chips (HA) and titanium. Stem cells were challenged with each engineered surface, either in plane cultures or in a rotating apparatus, for a month. Gingival fibroblasts were used as controls. Results showed that stem cells exerted a different response, depending on the different type of textured surface: in fact, microconcavities significantly affected SBP-DPSC differentiation into osteoblasts, both temporally and quantitatively, with respect to the other textured surfaces. Actually, stem cells challenged with concave surfaces differentiated quicker and showed nuclear polarity, an index of secretion, cellular activity and matrix formation. Moreover, bone-specific proteins were significantly expressed and the obtained bone tissue was of significant thickness. Thus, cells cultured on the concave textured surface had better cell-scaffold interactions and were induced to secrete factors that, due to their autocrine effects, quickly lead to osteodifferentiation, bone tissue formation, and vascularization. The worst cell performance was obtained using convex surfaces, due to the scarce cell proliferation on to the scaffold and the poor matrix secretion. In conclusion, this study stresses that for a suitable and successful bone tissue reconstruction the surface texture is of paramount importance.
Objectives : The aim of this study was to select and provide enough stem cells for quick transpla... more Objectives : The aim of this study was to select and provide enough stem cells for quick transplantation in bone engineering procedures, avoiding any in vitro expansion step. Materials and Methods : Dental germ pulp, collected from 25 healthy subjects aged 13–20 years, were subjected to magnetic-activated cell sorting to select a CD34 + stem cell population capable of differentiating into pre-osteoblasts. These cells were allowed to adhere to an absorbable polylactic–coglycolic acid scaffold for 30 min, without any prior expansion, and the CD34 + cell-colonized scaffolds were then transplanted into immuno-compromised rats, subcutaneously. Results : After 60 days, analysis of recovered transplants revealed that they were formed of nodules of bone, of the same dimensions as the original scaffold. Bone-specific proteins were detected by immunofluorescence, within the nodules, and X-ray diffraction patterns revealed characteristic features of bone. In addition, presence of platelet endothelial cell adhesion molecule and von Willebrand factor immunoreactivity were suggestive of neo-angiogenesis and neovasculogenesis taking place within nodules. Importantly, these vessels were HLA-1 + and, thus, clearly human in origin. Conclusions : This study indicates that CD34 + cells obtained from dental pulp can be used for engineering bone, without the need for prior culture expanding procedures. Using autologous stem cells, this schedule could be used to provide the basis for bone regenerative surgery, with limited sacrifice of tissue, low morbidity at the collection site, and significant reduction in time needed for clinical recovery.
Human tissues are different in term of regener-ative properties. Stem cells are a promising tool ... more Human tissues are different in term of regener-ative properties. Stem cells are a promising tool for tissue regeneration, thanks to their particular characteristics of proliferation, differentiation and plasticity. Several " loci " or " niches " within the adult human body are colonized by a significant number of stem cells. However, access to these potential collection sites often is a limiting point. The interaction with biomaterials is a further point that needs to be considered for the therapeutic use of stem cells. Dental pulp stem cells (DPSCs) have been demonstrated to answer all of these issues: access to the collection site of these cells is easy and produces very low morbidity; extraction of stem cells from pulp tissue is highly efficiency; they have an extensive differentiation ability; and the demonstrated interactivity with biomaterials makes them ideal for tissue reconstruction. SBP-DPSCs are a multipotent stem cell subpopulation of DPSCs which are able to differentiate into osteoblasts, synthesizing 3D woven bone tissue chips in vitro and that are capable to synergically differentiate into osteoblasts and endotheliocytes. Several studied have been performed on DPSCs and they mainly found that these cells are multipotent stromal cells that can be safety cryopre-served, used with several scaffolds, that can extensively proliferate, have a long lifespan and build in vivo an adult bone with Havers channels and an appropriate vasculariza-tion. A definitive proof of their ability to produce dentin has not been yet done. Interestingly, they seem to possess immunoprivileges as they can be grafted into allogenic tissues and seem to exert anti-inflammatory abilities, like many other mesenchymal stem cells. The easy management of dental pulp stem cells make them feasible for use in clinical trials on human patients.
Background: Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of het... more Background: Osteosarcoma is the most common primary tumour of bone. Solid tumours are made of heterogeneous cell populations, which display different goals and roles in tumour economy. A rather small cell subset can hold or acquire stem potentials, gaining aggressiveness and increasing expectancy of recurrence. The CD133 antigen is a pentaspan membrane glycoprotein, which has been proposed as a cancer stem cell marker, since it has been previously demonstrated to be capable of identifying a cancer initiating subpopulation in brain, colon, melanoma and other solid tumours. Therefore, our aim was to observe the possible presence of cells expressing the CD133 antigen within solid tumour cell lines of osteosarcoma and, then, understand their biological characteristics and performances.
Numerous stem cell niches are present in the different tissues and organs of the adult human body... more Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the 'sealed niche' of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca 2ϩ release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy.
Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Mo... more Background: Human adult adipose tissue is an abundant source of mesenchymal stem cells (MSCs). Moreover, it is an easily accessible site producing a considerable amount of stem cells.
In this study we used a biocomplex constructed from dental pulp stem/progenitor cells (DPCs) and ... more In this study we used a biocomplex constructed from dental pulp stem/progenitor cells (DPCs) and a collagen sponge scaffold for oro-maxillo-facial (OMF) bone tissue repair in patients requiring extraction of their third molars. The experiments were carried out according to our Internal Ethical Committee Guidelines and written informed consent was obtained from the patients. The patients presented with bilateral bone reabsorption of the alveolar ridge distal to the second molar secondary to impaction of the third molar on the cortical alveolar lamina, producing a defect without walls, of at least 1.5 cm in height. This clinical condition does not permit spontaneous bone repair after extraction of the third molar, and eventually leads to loss also of the adjacent second molar. Maxillary third molars were extracted first for DPC isolation and expansion. The cells were then seeded onto a collagen sponge scaffold and the obtained biocomplex was used to fill in the injury site left by extraction of the mandibular third molars. Three months after autologous DPC grafting, alveolar bone of patients had optimal vertical repair and complete restoration of periodontal tissue back to the second molars, as assessed by clinical probing and X-rays. Histological observations clearly demonstrated the complete regeneration of bone at the injury site. Optimal bone regeneration was evident one year after grafting. This clinical study demonstrates that a DPC/collagen sponge biocomplex can completely restore human mandible bone defects and indicates that this cell population could be used for the repair and/or regeneration of tissues and organs.
Bone Tissue Engineering (BTE) and Dental Implantology (DI) require the integration of implanted s... more Bone Tissue Engineering (BTE) and Dental Implantology (DI) require the integration of implanted structures, with well characterized surfaces, in bone. In this work we have challenged acid-etched titanium (AET) and Laser Sintered Titanium (LST) surfaces with either human osteoblasts or stem cells from human dental pulps (DPSCs), to understand their osteointegration and clinical use capability of derived implants. DPSCs and human osteoblasts were challenged with the two titanium surfaces, either in plane cultures or in a roller apparatus within a culture chamber, for hours up to a month. During the cultures cells on the titanium surfaces were examined for histology, protein secretion and gene expression. Results show that a complete osteointegration using human DPSCs has been obtained: these cells were capable to quickly differentiate into osteoblasts and endotheliocytes and, then, able to produce bone tissue along the implant surfaces. Osteoblast differentiation of DPSCs and bone morphogenetic protein production was obtained in a better and quicker way, when challenging stem cells with the LST surfaces. This successful BTE in a comparatively short time gives interesting data suggesting that LST is a promising alternative for clinical use in DI.
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Papers by Prof.Gianpaolo Papaccio