Dental Pulp Mesenchymal Stem Cells Research Articles

Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages

BackgroundCell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.MethodsHere, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells.For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes.ResultsWe found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45− stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes.ConclusionsOur results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells.

The effect of conditioned medium isolated from dental pulp mesenchymal stem cells (DPSC) treated with curcumin on oral pathogens

The effect of conditioned medium isolated from dental pulp mesenchymal stem cells (DPSC) treated with curcumin on oral pathogens

Optimizing biomaterial inks: A study on the printability of Carboxymethyl cellulose-Laponite nanocomposite hydrogels and dental pulp stem cells bioprinting

Tissue engineering approaches require biocompatible materials with precise pre-designed geometry, shape fidelity, and promote cellular functions. Addressing these requirements, our study focused on developing an optimized bioink formulation using carboxymethyl cellulose (CMC) and Laponite hydrogels tailored for extrusion-based three-dimensional bioprinting. To this, we investigated the rheological properties and filament behavior before and during printing. As Laponite concentration increased in CMC solutions, it improved shear-thinning behavior, viscosity, and storage modulus, resulting in well-defined filament characteristics with lower diffusion rates, excellent shape fidelity, and robust printability. Thus, we achieved a suitable biomaterial ink formulation with concentrations of 1 wt% of CMC and 4 wt% of Laponite (1C4L). Subsequently, a statistical analysis guided us to select the optimal parameters for large-scale construct printing: a nozzle speed of 5 mm/s, a print distance of 0.41 mm, and an extrusion multiplier of 1.35. After that, we enhanced the structural integrity of printed hydrogels through ionic crosslinking with calcium chloride (CaCl2) and citric acid (CA), revealing higher-strength hydrogels at higher concentrations of CaCl2. Finally, we have confirmed the groundbreaking potential of our bioink by integrating dental pulp mesenchymal stem cells (DPSC) into the 1C4L ink. Our bioprinted constructs showed optimized swelling, non-toxic effects, and retained excellent shape fidelity, crucial for creating anatomically accurate tissues. Our findings provide crucial insights linking the rheological analysis, the bioprinting process, and the biological properties of hydrogels, paving the way for their use for tissue engineering and other biomedical applications.

Youthful small extracellular vesicles restore the function and reparative capacity of inflammatory-impaired periodontal ligament stem cells via delivering protein biglycan for bone regeneration

Regenerating inflamed bone defects represents a severe clinical challenge due to the undesirable inflammatory microenvironment. The inflammatory stimulus poses a weighty threat to the regenerative capacity of endogenously derived mesenchymal stem cells (MSCs), which are mainly responsible for osteogenic differentiation, thereby resulting in compromised endogenous bone formation. Consequently, alleviating the biological characteristics of inflammatory-impaired MSCs is crucial for promoting inflamed bone regeneration. Nano-sized small extracellular vesicles (sEVs) have emerged as promising therapeutic tools to orchestrate MSCs fate due to their intrinsic biocompatibility and encapsulated bioactive contents. In the present study, we extracted sEVs from youthful and adult dental pulp MSCs and explored their ability to recover inflammation-compromised periodontal ligament stem cells (IPDLSCs). The results indicated that both types of sEVs were capable of facilitating IPDLSCs osteogenesis. However, young sEVs exhibited a more robust potential at a lower concentration compared to adult sEVs. Mechanically, young sEVs enhanced the expression of bone morphogenetic protein 4 (BMP4) via delivering the protein Biglycan, which correspondingly promoted the osteogenic capability of IPDLSCs. Collectively, our findings emphasized that young sEVs hold enormous potential to rescue the inherent function and regenerative competence of inflammation-impaired MSCs, shedding light on their promising therapeutic prospects for infected bone regeneration.

Decellularized leaf-based biomaterial supports osteogenic differentiation of dental pulp mesenchymal stem cells.

Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue, high costs and ethical concerns related to the use of animal sources. Plant-based tissue decellularized scaffolds could be a better option to overcome the problem. The leaves of different plants offer a unique opportunity for the development of tissue-specific scaffolds, depending on the reticulate or parallel veination. Herein, we decellularized spinach leaves and employed thesefor the propagation and osteogenic differentiation of dental pulp stem cells (DPSCs). DPSCs were characterized by using mesenchymal stem cell surface markers CD90, CD105 and CD73 and CD34, CD45 and HLA-DR using flow cytometry. Spinach leaves were decellularized using ethanol, NaOH and HCL. Cytotoxicity of spinach leaf scaffolds were analysed by MTT assay. Decellularized spinach leaves supported dental pulp stem cell adhesion, proliferation and osteogenic differentiation. Our data demonstrate that the decellularized spinach cellulose scaffolds can stimulate the growth, proliferation and osteogenic differentiation of DPSCs. In this study, we showed the versatile nature of decellularized plant leaves as a biological scaffold and their potential for bone regeneration in vitro.

Dental pulp mesenchymal stem cells-response to fibrin hydrogel reveals ITGA2 and MMPs expression

Regenerative endodontic procedures (REP) aim at reestablishing tooth vitality by replacing the irreversibly damaged dental pulp removed by the dental practitioner with a new functional one. The current treatment of advanced caries relies on the replacement of the inflamed or necrosed dental pulp with an inert filling material. This leads to a functional but non-vital tooth, which lacks the ability to sense dental tissue damage, and to protect from further bacterial attack. Therapeutic strategies inspired by tissue engineering called REP propose to regenerate a fully functional dental pulp directly in the canal space. Promising results were obtained using dental pulp mesenchymal stem cells (DP-MSCs) in combination with bio-inspired artificial and temporary 3D hydrogels made of extracellular matrix molecules such as collagen and fibrin biomacromolecules. However, the uncontrolled mechanisms of DP regeneration from DP-MSCs in 3D biomacromolecules fail to regenerate a fully functional DP and can induce fibrotic scarring or mineralized tissue formation to a non-negligible extent. The lack of knowledge regarding the early molecular mechanisms initiated by DP-MSCs seeded in ECM-made hydrogels is a scientific lock for REP. In this study, we investigated the early DP-MSC–response in a 3D fibrin hydrogel. DP-MSCs isolated from human third molars were cultured for 24 h in the fibrin hydrogel. The differential transcript levels of extracellular and cell surface genes were screened with 84-gene PCR array. Out of the 84 genes screened, 9 were found to be overexpressed, including those coding for the integrin alpha 2 subunit, the collagenase MMP1 and stromelysins MMP3, MMP10 and MMP12. Over-expression of ITGA2 was confirmed by RT-qPCR. The expression of alpha 2 integrin subunit protein was assessed over time by immunoblot and immunofluorescence staining. The increase in the transcript level of MMP1, MMP3, MM10 and MMP12 was confirmed by RT-qPCR. The overexpression of MMP1 and 3 at the protein level was assessed by immunoblot. MMP3 expression by DP-MSCs was observed by immunofluorescence staining. This work demonstrates overexpression of ITGA2 and of MMP1, 3, 10 and 12 by DP-MSCs cultured in a fibrin hydrogel. The main preliminary extracellular and cell surface response of the DP-MSCs to fibrin hydrogel seems to rely on a ITGA2/MMP3 axis. Further investigations are needed to precisely decipher the role of this axis in dental pulp tissue building. Nevertheless, this work identifies extracellular and cell surface molecules that could be potential checkpoints to be targeted to guide proper dental pulp tissue regeneration.

Extracellular vesicles from dental pulp mesenchymal stem cells modulate macrophage phenotype during acute and chronic cardiac inflammation in athymic nude rats with myocardial infarction

Background/aimsExtracellular vesicles (EVs) derived from dental pulp mesenchymal stem cells (DP-MSCs) are a promising therapeutic option for the treatment of myocardial ischemia. The aim of this study is to determine whether MSC-EVs could promote a pro-resolving environment in the heart by modulating macrophage populations.MethodsEVs derived from three independent biopsies of DP-MSCs (MSC-EVs) were isolated by tangential flow-filtration and size exclusion chromatography and were characterized by omics analyses. Biological processes associated with these molecules were analyzed using String and GeneCodis platforms. The immunomodulatory capacity of MSC-EVs to polarize macrophages towards a pro-resolving or M2-like phenotype was assessed by evaluating surface markers, cytokine production, and efferocytosis. The therapeutic potential of MSC-EVs was evaluated in an acute myocardial infarction (AMI) model in nude rats. Infarct size and the distribution of macrophage populations in the infarct area were evaluated 7 and 21 days after intramyocardial injection of MSC-EVs.ResultsLipidomic, proteomic, and miRNA-seq analysis of MSC-EVs revealed their association with biological processes involved in tissue regeneration and regulation of the immune system, among others. MSC-EVs promoted the differentiation of pro-inflammatory macrophages towards a pro-resolving phenotype, as evidenced by increased expression of M2 markers and decreased secretion of pro-inflammatory cytokines. Administration of MSC-EVs in rats with AMI limited the extent of the infarcted area at 7 and 21 days post-infarction. MSC-EV treatment also reduced the number of pro-inflammatory macrophages within the infarct area, promoting the resolution of inflammation.ConclusionEVs derived from DP-MSCs exhibited similar characteristics at the omics level irrespective of the biopsy from which they were derived. All MSC-EVs exerted effective pro-resolving responses in a rat model of AMI, indicating their potential as therapeutic agents for the treatment of inflammation associated with AMI.

Comparative evaluation of bone marrow and dental pulp mesenchymal stem cells for motor functional recovery in rat sciatic nerve injury.

This study delves into the impact of mesenchymal stem cells derived from bone marrow (BM-MSCs) and those sourced from dental pulp (DP-MSCs) on the recovery of motor function and morphological aspects of the rat's sciatic nerve after crush injuries. The findings highlight that the groups treated with BM-MSCs, DP-MSCs or a combination of both (BM + DP-MSCs) displayed enhanced sciatic functional index values when juxtaposed with the sham group. This points to bettered motor functionalities. A deeper morphological analysis showed that all the groups had retained perineurium structure and fascicular arrangement. Notably, the sham and BM-MSCs groups had very few inconsistencies. All groups showed standard vascular density. Remarkably, the combined treatment group (BM + DP-MSCs) presented diminished oedema and a lower count of inflammatory cells. Through immunohistochemical methods, the presence of S100 expression was noted in the groups that underwent treatment. In summation, the study suggests that both BM-MSCs and DP-MSCs, whether used singly or in combination, can significantly aid in motor function restoration and morphological enhancements. An interesting observation from our research and earlier studies is that stem cells from dental pulp, which are sourced with less discomfort from milk and wisdom teeth, show a heightened propensity to evolve into nerve cells. This is in contrast to the more uncomfortably acquired BM-MSCs.

LIM homeobox 8 reduced apoptosis and promoted periodontal tissue regeneration function of dental pulp stem cells

Stem cell-mediated tissue regeneration is a promising strategy for repairing tissue defects and functional reconstruction in periodontitis, a common disease that leads to the loss of alveolar bone and teeth. However, stem cell apoptosis, widely observed during tissue regeneration, impairs its efficiency. Therefore, the regulation of stem cell apoptosis is critical for improving regeneration efficiency. The LIM homeobox 8 gene LHX8, belongs to the LIM homeobox family, which was involved in tooth morphogenesis. Here, we found that LHX8 was significantly expressed in dental pulp. LHX8 knockdown significantly increased dental pulp mesenchymal stem cells (DPSCs) apoptosis, as confirmed by RT-PCR, western blotting, flow cytometry, and transmission electron microscopy. Additionally, LHX8 overexpression inhibited apoptosis and enhanced the osteo/odontogenic differentiation potential of hDPSCs in vitro. Furthermore, LHX8-overexpression could enhance the periodontal tissue regeneration efficiency of hDPSCs in mice with periodontitis. In conclusion, the present study indicates that LHX8 inhibits stem cell apoptosis and promotes functional tissue formation in stem cell-based tissue regeneration engineering, suggesting a new therapeutic target to increase the efficacy of periodontal tissue regeneration.

Protective effect of dental pulp stem cells' conditioned medium against cisplatin-induced testicular damage in rats

Cisplatin is a highly effective chemotherapy drug used to treat most solid tumors. However, one of its side effects is testicular toxicity, which can lead to fertility abnormalities. This study investigated the effectiveness of dental pulp mesenchymal stem cells conditioned medium (DPSC-CM) on cisplatin-induced testicular toxicity. In this study, 36 eight-week-old male Wistar rats were randomly divided into three groups equally (n = 12). Group 1 control "CTR", which received normal saline (0.5 ml) intraperitoneally (i.p), group 2 "Cis" which received an intraperitoneal dose of cisplatin (7 mg/kg), and group 3 "Cis+CM" which received an i.p injection of DPSC-CM (0.5 mg/kg) after cisplatin injection. Biochemical, histomorphometric, and histopathological studies were performed on the testis. Our results exhibited that cis administration led to a decline in total body weight, testis weight, diameter, and volume. A decrease in testosterone and IL-6 serum levels, as well as a decrease in IL-6 and TNFα levels, the activity of catalase and SOD enzymes, and an increase in MDA in testicular tissue were detected. Testicular tissue damage was associated with a significant decrease in tube diameter, germinal epithelium height, number of spermatogonia and Sertoli cells, along with a noticeable increase in basement membrane thickness, and perivascular fibrosis. DMSC-CM improved all the mentioned parameters. Taken together, our results demonstrated that DMSC-CM due to its antioxidant and anti-inflammatory properties, could be effective in reversing cisplatin-induced testicular toxicity.

Acetylsalicylic Acid Promotes Osteogenic Differentiation of Human Dental Pulp Mesenchymal Stem Cells and Regeneration of Alveolar Bone in Experimental Periodontitis Rats

Background. Periodontitis is characterized by bone resorption and periodontal tissue destruction owing to oral microbiota, mechanical stress, and systemic diseases such as diabetes mellitus. Human dental pulp mesenchymal stem cells (hDPMSCs) were analyzed as potential candidates for periodontal tissue regeneration. Acetylsalicylic acid (ASA), also known as aspirin, has been shown to promote osteogenic differentiation of mesenchymal stem cells. We investigated the effect of ASA pretreatment on periodontitis in order to achieve a more appealing prognosis of bone resorption. Methods. The effect of ASA on cell proliferation was detected by the CCK-8 assay, and alkaline phosphatase (ALP) staining, alizarin red staining (ARS), and western blot were used to investigate the effect of different ASA concentrations on hDPMSCs’ osteogenic differentiation and possible signaling pathways. Periodontitis was induced for 4 weeks. Stem cells pretreated with 50 µg/mL of ASA were transplanted into six-week-old male Sprague-Dawley rats by local and systemic injection once a week for two weeks. Four weeks after cell therapy, the rats were sacrificed for sampling to complete the molecular and morphological experiments. Results. In vitro experiments revealed that 50 µg/mL of ASA had a significant effect on cell osteogenic differentiation. That is, when ASA was administered, the MAPK signaling pathway was activated. Notably, further vivo experiments revealed that ASA-hDPMSCs increased the area of bone regeneration and the OPG/RANKL ratio, suppressed TNF-α and IL-1 expression, and promote alveolar bone repair. Conclusion. Our study extends the findings of previous research, firstly demonstrating that the use of ASA-pretreated hDPMSCs offers a novel therapy for the treatment of periodontitis for future clinical application.

Intravenous human dental pulp-derived mesenchymal stem cell therapy for ischemic stroke in rats: an analysis of functional and ischemic brain areas outcomes

Cellular therapies have been implicated in treating and rehabilitating ischemic stroke (IS), involving the basic experimental and preclinical areas. Using mesenchymal stem cells (MSC) derived from human dental pulp has shown promising results in animal models, but still with mechanisms and consequences that are not entirely clear. The study aims to evaluate the effects of intravenous MSC on rats with IS regarding neurological function and histological areas of ischemia. Thirty-two male Wistar rats underwent temporary occlusion of the middle cerebral artery (TOMCA) for 60 minutes and were divided into two groups of 16 animals each. One group received dental pulp MSC intravenously, and another received saline 2 hours after TOMCA. The animals were then evaluated using the neurological functionality scales for 15 days, and at the end of the experiment period, the histological areas of cerebral ischemia were analysed. All animals presented ischemic areas and neurological deficits compatible with IS. There was partial recovery of the functionality scores over the evaluation period, and all animals presented focal cerebral ischemia measured by histological analysis; however, there was no statistical difference between the groups. The TOMCA model was effective in reproducing IS. Although we found no difference between treatment groups, our results were useful in showing the pattern of neurological recovery presented by animals treated with dental pulp MSC and the need to extend the evaluation time for a longer period and use more sensitive functional tests. The results add valuable data for improving research with dental pulp MSC in the murine model of IS.

Vitamin D3-incorporated chitosan/collagen/fibrinogen scaffolds promote angiogenesis and endothelial transition via HIF-1/IGF-1/VEGF pathways in dental pulp stem cells

Effective vascularization during wound healing remains a critical challenge in the regeneration of skin tissue. On the other hand, mesenchymal stem cell (MSC) to endothelial phenotype transition (MEnDoT) is a potential phenomenon grossly underexplored in vascularized skin tissue engineering. Vitamin D3 has a proven role in promoting MEnDoT. Hence, a D3-incorporated scaffold made with biocompatible materials such as chitosan, collagen and fibrinogen should be able to promote endothelial lineage transition in vitro for tissue engineering purposes. In this study, we developed vitamin D3 incorporated chitosan-collagen-fibrinogen (CCF-D3) scaffolds physically crosslinked under UV and conducted thorough physicochemical and biological assays on it compared to a control scaffold without vitamin D3. Our study for the first time reports the potential vascularization property of the CCF-D3 scaffold by inducing the transitions of dental pulp MSC to endothelial lineage via the HIF-1/IGF-1/VEGF pathways. MSC seeded on UV-exposed CCF-D3 scaffolds had higher cell viability and transitioned towards endothelial lineage was observed by elevated proliferative and endothelial-specific gene expressions and flow cytometric analysis of SCA-1+ antibody. The difference in VEGF-A and α-SMA expressions was also observed in the D3-CCF scaffold compared to the scaffolds without D3.

Fluconazole-Induced Protein Changes in Osteogenic and Immune Metabolic Pathways of Dental Pulp Mesenchymal Stem Cells of Osteopetrosis Patients.

Osteopetrosis is a rare inherited disease caused by osteoclast failure, resulting in increasing bone density in humans. Patients with osteopetrosis possess several dental and cranial complications. Since carbonic anhydrase II (CA-II) deficiency is a major cause of osteopetrosis, CA-II activators might be an attractive potential treatment option for osteopetrosis patients. We conducted comprehensive label-free quantitative proteomics analysis on Fluconazole-treated Dental Pulp Mesenchymal Stem/Stromal Cells from CA-II-Deficient Osteopetrosis Patients. We identified 251 distinct differentially expressed proteins between healthy subjects, as well as untreated and azole-treated derived cells from osteopetrosis patients. Twenty-six (26) of these proteins were closely associated with osteogenesis and osteopetrosis disease. Among them are ATP1A2, CPOX, Ap2 alpha, RAP1B and some members of the RAB protein family. Others include AnnexinA1, 5, PYGL, OSTF1 and PGAM4, all interacting with OSTM1 in the catalytic reactions of HCO3 and the Cl- channel via CAII regulation. In addition, the pro-inflammatory/osteoclast regulatory proteins RACK1, MTSE, STING1, S100A13, ECE1 and TRIM10 are involved. We have identified proteins involved in osteogenic and immune metabolic pathways, including ERK 1/2, phosphatase and ATPase, which opens the door for some CA activators to be used as an alternative drug therapy for osteopetrosis patients. These findings propose that fluconazole might be a potential treatment agent for CAII- deficient OP patients. Altogether, our findings provide a basis for further work to elucidate the clinical utility of azole, a CA activator, as a therapeutic for OP.

Human Dental Pulp Mesenchymal Stem Cell-Derived Soluble Factors Combined with a Nanostructured Scaffold Support the Generation of a Vascular Network In Vivo.

Among all strategies directed at developing new tools to support re-vascularization of damaged tissues, the use of pro-angiogenic soluble factors, derived from mesenchymal stem cells (MSCs), appears a promising approach for regenerative medicine. Here, we compared the feasibility of two devices, generated by coupling soluble factors of human dental pulp mesenchymal stem cells (DPSCs), with a nanostructured scaffold, to support angiogenesis once transplanted in mice. DPSCs were obtained from impacted wisdom tooth removal, usually considered surgical waste material. After 28 days, we verified the presence of active blood vessels inside the scaffold through optical and scansion electron microscopy. The mRNA expression of surface antigens related to macrophage polarization (CD68, CD80, CD86, CD163, CD206), as well as pro-angiogenic markers (CD31, CD34, CD105, Angpt1, Angpt2, CDH5) was evaluated by real-time PCR. Our results demonstrate the capability of DPSC-scaffold and DPSC soluble factors-scaffold to support angiogenesis, similarly to adipose stem cells, whereas the absence of blood vessels was found in the scaffold grafted alone. Our results provide evidence that DPSC-conditioned medium can be proposed as a cell-free preparation able to support angiogenesis, thus, providing a relevant tool to overcome the issues and restrictions associated with the use of cells.

Osteogenic differentiation enhancement of human dental pulp mesenchymal stem cells: A review

Background: The article aims to review osteogenic differentiation enhancement in human Dental Pulp Mesenchymal Stem Cells (hDPMSCs). Material and Methods: The literature review was carried out in PUBMED with the keywords: human Dental Pulp Mesenchymal Stem Cells (hDPMSCs) and osteogenic differentiation. Conclusions: Many research investigated the impact of different compounds on the osteogenic differentiation of hDPMSCs and the appliance by which these compounds promote osteogenesis in hDPMSCs which are a potential source for bone regeneration.

Statement of Retraction: A new Zn(II) complex: promotion on the reconstruction of oral bone tissue via inducing the dental pulp mesenchymal stem cells differentiation

Statement of Retraction: A new Zn(II) complex: promotion on the reconstruction of oral bone tissue via inducing the dental pulp mesenchymal stem cells differentiation

Conditioned Media from Human Pulp Stem Cell Cultures Improve Bone Regeneration in Rat Calvarial Critical-Size Defects.

The aim of this study was to test whether lyophilized conditioned media from human dental pulp mesenchymal stem cell cultures promote the healing of critical-size defects created in the calvaria of rats. Prior to the surgical procedure, the medium in which dental pulp stem cells were cultured was frozen and lyophilized. After general anesthesia, an 8 mm diameter bone defect was created in the calvaria of twenty-four rats. The defects were filled with the following materials: xenograft alone (G1) or xenograft associated with lyophilized conditioned medium (G2). After 14 or 42 days, the animals were euthanized, and the specimens processed for histologic and immunohistochemical analysis. Bone formation at the center of the defect was observed only in the G2 at 42 days. At both timepoints, increased staining for VEGF, a marker for angiogenesis, was observed in G2. Consistent with this, at 14 days, G2 also had a higher number of blood vessels detected by immunostaining with an anti-CD34 antibody. In conclusion, conditioned media from human dental pulp mesenchymal stem cell cultures had a positive effect on the regenerative process in rat critical-size bone defects. Both the formation of bone and enhancement of vascularization were stimulated by the conditioned media.

Volumetry of ovine incisors dental pulp for further regenerative therapy.

Mesenchymal stem cells (MSCs) are used for regenerative therapy. Dental pulp MSCs make extracted wisdom teeth a useful resource in humans. Preclinical validation of regenerative therapies requires large animal models such as the sheep. Since stem cells can be retrieved from the dental pulp of ovine incisors, the best age to extract a maximal volume of dental pulp needs to be defined. The objective of this ex vivo study was to quantify incisors dental pulp volume, in sheep of various age. Three jaws were dedicated to histology (one per age group); the others were imaged with a computed tomography scanner [3 years-old (n = 9), 4 (n = 3) and 6 (n = 5)]. The incisors dental pulp volume was measured after 3D reconstruction. Multiple linear regression showed that dental pulp volume of ovine incisors decreases with age (β-estimate = -3.3; p < 0.0001) and teeth position from the more central to the more lateral (β-estimate = -4.9; p = 0.0009). Weight was not a relevant variable in the regression model. The dental pulp volume ranged from 36.7 to 19.6 mm3 in 3-year-old sheep, from 23.6 to 11.3 in 4-year-old sheep, and from 19.4 to 11.5 in 6-year-old sheep. The pulp volume of the most central teeth (first intermediate) was significantly higher than the most lateral teeth (corner). Haematoxylin-Eosin-Safran of the whole incisors, and of isolated dental pulps demonstrated a similar morphology to that in humans. The first intermediate incisor of 3-year-old sheep should be selected preferentially in preclinical research to retrieve the highest volume of dental pulp.

Corrigendum to: Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano.

In this correction, the Editor in Chief suggested revising the publication of Figures 3 and 8E in the article after the correction in numeric value. Below is the corrected version of the figures [1]. The electronic version of the article can be found in "Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano" in the journal Current Gene Therapy, 2018, 18(5), 307-323. Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The original article can be found online at: https://www.eurekaselect.com/article/93056.