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school of dentistry
Research Institute of dental sciences, Shahid Beheshti University of Medical Sciences
dental stem cells, tissue engineering, dental stem cell banking, cell therapy, regenerative dentistry
Majid Salehi, Farshid Bastami, Maryam Rezai Rad, Hanieh Nokhbatolfoghahaei, Zahrasadat Paknejad, Pantea Nazeman, Ali Hassani, and Arash Khojasteh
Polymers for Advanced Technologies, ISSN: 10427147, eISSN: 10991581, Published: 2020 Wiley
Ziba Naghizadeh, Akbar Karkhaneh, Hanieh Nokhbatolfoghahaei, Saeed Farzad‐Mohajeri, Maryam Rezai‐Rad, Mohammad M. Dehghan, Pouyan Aminishakib, and Arash Khojasteh
Journal of Cellular Physiology, ISSN: 00219541, eISSN: 10974652, Published: 2020 Wiley
In this study, we developed an injectable in situ forming hydrogel/microparticle system consisting of two drugs, melatonin and methylprednisolone, to investigate the capability of the system for chondrogenesis in vitro and in vivo. The chemical, mechanical, and rheological properties of the hydrogel/microparticle were investigated. For in vitro evaluation, the adipose-derived stem cells might be mixed with hydrogel/microparticles, then cellular viability was analyzed by acridine orange/propidium iodide and 4',6-diamidino-2-phenylindole staining and also dimethylmethylene blue assay were conducted to find the amount of proteoglycan. The real-time polymerase chain reaction for aggrecan, sex-determining region Y-Box 9, collagen I (COL1), and COL2 gene expression was performed after 14 and 21 days. For evaluation of cartilage regeneration, the samples were implanted in rabbit knees with cartilaginous experimental defects. Defects were created in both knees of three groups of rabbits. Group 1 was the control with no injection, and Groups 2 and 3 were loaded with hydrogel/cell and hydrogel/microparticle/cell; respectively. Then, after 3 and 6 months, histological evaluations of the defected sites were carried out. The amount of glycosaminoglycans after 14 and 21 days increased significantly in hydrogels/microparticles loaded with cells. The expression of marker genes was also significant in hydrogels/microparticles loaded with cells. According to histology analysis, the hydrogels/microparticles loaded with cells showed the best cartilage regeneration. Overall, our study revealed that the developed injectable hydrogel/microparticle can be used for cartilage regeneration.
Hanieh Nokhbatolfoghahaei, Mahboubeh Bohlouli, Kazem Adavi, Zahrasadat Paknejad, Maryam Rezai Rad, Mohammad Mehdi khani, Nasim Salehi-Nik, and Arash Khojasteh
Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, ISSN: 09544119, eISSN: 20413033, Published: 2020 SAGE Publications
Bioreactor system has been used in bone tissue engineering in order to simulate dynamic nature of bone tissue environments. Perfusion bioreactors have been reported as the most efficient types of shear-loading bioreactor. Also, combination of forces, such as rotation plus perfusion, has been reported to enhance cell growth and osteogenic differentiation. Mathematical modeling using sophisticated infrastructure processes could be helpful and streamline the development of functional grafts by estimating and defining an effective range of bioreactor settings for better augmentation of tissue engineering. This study is aimed to conduct computational modeling for newly designed bioreactors in order to alleviate the time and material consuming for evaluating bioreactor parameters and effect of fluid flow hydrodynamics (various amounts of shear stress) on osteogenesis. Also, biological assessments were performed in order to validate similar parameters under implementing the perfusion or rotating and perfusion fluid motions in bioreactors’ prototype. Finite element method was used to investigate the effect of hydrodynamic of fluid flow inside the bioreactors. The equations used in the simulation to calculate the velocity values and consequently the shear stress values include Navier–Stokes and Brinkman equations. It has been shown that rotational fluid motion in rotating and perfusion bioreactor produces more velocity and shear stress compared with perfusion bioreactor. Moreover, implementing the perfusion together with rotational force in rotating and perfusion bioreactors has been shown to have more cell proliferation and higher activity of alkaline phosphatase enzyme as well as formation of extra cellular matrix sheet, as an indicator of bone-like tissue formation.
Fahimeh Akhlaghi, Nima Hesami, Maryam Rezai Rad, Pantea Nazeman, Farahnaz Fahimipour, and Arash Khojasteh
Journal of Cranio-Maxillofacial Surgery, ISSN: 10105182, eISSN: 18784119, Pages: 1266-1273, Published: August 2019 Elsevier BV
BACKGROUND Human amniotic membranes (HAMs), as a biological membrane with healing, osteogenic, and cell therapy potential, has been in the spotlight to enhance the outcomes of treating bone defects. Present study aims to clinically assess the potential of HAM loaded with buccal fat pad-derived stem cells (BFSCs) as an osteogenic coverage for onlay bone grafts to maxillomandibular bone defects. MATERIALS AND METHODS Nine patients with jaw bone defects were enrolled in the present study. The patients were allocated to two study groups: Iliac crest bone graft with HAM coverage (n = 5), and Iliac bone grafts covered with HAM loaded with BFSCs (n = 4). Five months following the grafting and prior to implant placement, cone beam computed tomography was performed for radiomorphometric analysis. RESULTS The mean increase in bone width was found to be significantly greater in the HAM + BFSCs group (4.42 ± 1.03 mm versus 3.07 ± 0.73 mm, p < 0.05). Further, the changes in vertical dimension were greater in the HAM + BFSCs group (4.66 ± 1.06 mm versus 4.14 ± 1.03 mm, p > 0.05). CONCLUSION Combined use of HAM with mesenchymal stem cells may enhance bone regeneration specifically in the horizontal dimension. Moreover, this methodology reduces the amount of harvested autogenous bone and diminish secondary bone resorption.
Shervin Shafiei, Meisam Omidi, Fatemeh Nasehi, Hossein Golzar, Dorsa Mohammadrezaei, Maryam Rezai Rad, and Arash Khojasteh
Materials Science and Engineering C, ISSN: 09284931, eISSN: 18730191, Volume: 100, Pages: 564-575, Published: July 2019 Elsevier BV
Recent exciting findings of the particular properties of Carbon dot (CDs) have shed light on potential biomedical applications of CDs-containing composites. While CDs so far have been widely used as biosensors and bioimaging agents, in the present study for the first time, we evaluate the osteoconductivity of CDs in poly (ε-caprolactone) (PCL)/polyvinyl alcohol (PVA) [PCL/PVA] nanofibrous scaffolds. Moreover, further studies were performed to evaluate egg shell-derived calcium phosphate (TCP3) and its cellular responses, biocompatibility and in vitro osteogenesis. Scaffolds were fabricated by simultaneous electrospinning of PCL with three different types of calcium phosphate, PVA and CDs. Fabricated scaffolds were characterized by Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), contact angle measurement and degradation assessment. SEM, the methyl thiazolyl tetrazolium (MTT) assay, and alkaline phosphatase (ALP) activity test were performed to evaluate cell morphology, proliferation and osteogenic differentiation, respectively. The results demonstrated that while the addition of just 1 wt% CDs and TCP3 individually into PCL/PVA nanocomposite enhanced ALP activity and cell proliferation rate (p < 0.05), the synergetic effect of CDs/TCP3 led to highest osteogenic differentiation and proliferation rate compared to other scaffolds (p < 0.05). Hence, CDs and PCL/PVA-TCP3 could serve as a potential candidate for bone tissue regeneration.
Arash Khojasteh, Sepanta Hosseinpour, Maryam Rezai Rad, Marzieh Alikhasi, and Homayoun H. Zadeh
Clinical Implant Dentistry and Related Research, ISSN: 15230899, eISSN: 17088208, Pages: 292-300, Published: April 2019 Wiley
BACKGROUND Application of adipose-derived stem cells originated from buccal fat pad (BFP) can simplify surgical procedures and diminish clinical risks compared to large autograft harvesting. PURPOSE This study sought to evaluate and compare the efficacy of buccal fat pad-derived stem cells (BFPSCs) in combination with anorganic bovine bone mineral (ABBM) for vertical and horizontal augmentation of atrophic posterior mandibles. MATERIALS AND METHODS Fourteen patients with atrophic posterior mandible were elected for this prospective exploratory study. BFP (3-5 mL) was harvested and BFPSCs were isolated and combined with ABBM at 50% ratio. The vertical and horizontal alveolar deficiencies were augmented by 50% mixture of ABBM with either BFPSCs (group 1) or particulated autologous bone (group 2). Titanium mesh was contoured to the desired 3D shape of the alveolar ridge and fixated to the host sites over the graft material of the two groups. At first, the amount of new bone areas was calculated by quantitative analysis of cone beam computed tomography (CBCT) images that were taken 6 months postoperatively according to regenerative techniques (group 1 vs group 2 without considering the type of bone defects). Second, these amounts were calculated in each group based on the type of defects. RESULTS Quantitative analysis of CBCT images revealed the areas of new bone formation were 169.5 ± 5.90 mm2 and 166.75 ± 10.05 mm2 in groups 1 and 2, respectively. The area of new bone formation for vertical defects were 164.91 ± 3.74 mm2 and 169.36 ± 12.09 mm2 in groups 1 and 2, respectively. The area of new bone formation for horizontal deficiencies were 170.51 ± 4.54 mm2 and 166.98 ± 9.36 mm2 in groups 1 and 2, respectively. There were no statistically significant differences between the two groups in any of the pair-wise comparisons (P > 0.05). CONCLUSIONS The findings of the present study demonstrated lack of difference in bone volume formation between BFPSCs and autologous particulate bone in combination with ABBM. If confirmed by future large-scale clinical trial, BFPSCs may provide an alternative to autogenous bone for reconstruction of alveolar ridge defects.
Arash Khojasteh, Sepanta Hosseinpour, Maryam Rezai Rad, and Marzieh Alikhasi
Journal of Oral Implantology, ISSN: 01606972, eISSN: 15481336, Pages: 45-54, Published: February 2019 American Academy of Implant Dentistry
This case report seeks to describe efficient clinical application of adipose-derived stem cells (AdSCs) originated from buccal fat pad (BFP) in combination with conventional guided bone regeneration as protected healing space for reconstruction of large alveolar defects after extraction of multiple impacted teeth. The first case was a 19-year-old woman with several impacted teeth in the maxillary and mandibular regions, which could not be forced to erupt and were recommended for surgical extraction by the orthodontist. After this procedure, a large bone defect was created, and this space was filled by AdSC loaded natural bovine bone mineral (NBBM), which was protected with lateral ramus cortical plates, microscrews, and collagen membrane. After 6 months of post-guided bone regeneration, the patient received 6 and 7 implant placements, respectively, in the maxilla and mandible. At 10 months postoperatively, radiographic evaluation revealed thorough survival of implants. The second case was a 22-year-old man with the same complaint and large bony defects created after his teeth were extracted. After 6 months of post-guided bone regeneration, he received 4 dental implants in his maxilla and 7 implants in the mandible. At 48 months postoperatively, radiographs showed complete survival of implants. This approach represented a considerable amount of 3-dimensional bone formation in both cases, which enabled us to use dental implant therapy for rehabilitation of the whole dentition. The application of AdSCs isolated from BFP in combination with NBBM can be considered an efficient treatment for bone regeneration in large alveolar bone defects.
Dorsa Mohammadrezaei, Hossein Golzar, Maryam Rezai Rad, Meisam Omidi, Hamid Rashedi, Fatemeh Yazdian, Arash Khojasteh, and Lobat Tayebi
Journal of Biomedical Materials Research - Part A, ISSN: 15493296, eISSN: 15524965, Volume: 106, Pages: 2284-2343, Published: August 2018 Wiley
Graphene and its derivatives have been well-known as influential factors in differentiating stem/progenitor cells toward the osteoblastic lineage. However, there have been many controversies in the literature regarding the parameters effect on bone regeneration, including graphene concentration, size, type, dimension, hydrophilicity, functionalization, and composition. This study attempts to produce a comprehensive review regarding the given parameters and their effects on stimulating cell behaviors such as proliferation, viability, attachment and osteogenic differentiation. In this study, a systematic search of MEDLINE database was conducted for in vitro studies on the use of graphene and its derivatives for bone tissue engineering from January 2000 to February 2018, organized according to the PRISMA statement. According to reviewed articles, different graphene derivative, including graphene, graphene oxide (GO) and reduced graphene oxide (RGO) with mass ratio ≤1.5 wt % for all and concentration up to 50 μg/mL for graphene and GO, and 60 μg/mL for RGO, are considered to be safe for most cell types. However, these concentrations highly depend on the types of cells. It was discovered that graphene with lateral size less than 5 µm, along with GO and RGO with lateral dimension less than 1 µm decrease cell viability. In addition, the three-dimensional structure of graphene can promote cell-cell interaction, migration and proliferation. When graphene and its derivatives are incorporated with metals, polymers, and minerals, they frequently show promoted mechanical properties and bioactivity. Last, graphene and its derivatives have been found to increase the surface roughness and porosity, which can highly enhance cell adhesion and differentiation. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2284-2343, 2018.
Sepanta Hosseinpour, Maryam Rezai Rad, Arash Khojasteh, and Homayoun H. Zadeh
Current Stem Cell Research and Therapy, ISSN: 1574888X, Pages: 292-315, Published: 1 May 2018 Bentham Science Publishers Ltd.
BACKGROUND Currently, antibodies are progressively applied in medicine for different purposes, including diagnostic and therapeutic indications. Over twenty monoclonal antibodies utilized for many therapeutic reasons from therapy of cancers, immune disorders, and osteoporosis to localized bony defects. In addition, therapeutic antibodies represented various findings in bone tissue engineering. OBJECTIVES The current study aims to systematically review the available literature on antibody assisted bone regeneration in animal models. METHODS A through electronic search was conducted from January 1992 to June 2017 limited to English language publications on administrations of antibodies for bone regeneration. Data extraction was ere performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS Twenty studies were selected and analyzed in this systematic review. Among these studies, six articles reported in vitro results in addition to in vivo evaluations. The data is tabulated according to the route of administrations as locally administrated antibody which includes anti-bone morphogenetic protein 2 (anti-BMP2) and systemic administrated antibodies, which include anti-sclerostin and anti- Dickkopf-1 (DKK1). Data are summarized and reported by the following variables: Type of study, types of cells for in vitro investigations, types of animal models and defects characteristics, types of scaffolds used in the defect site, duration of follow-ups; and outcomes of assessments. CONCLUSIONS A novel approach of administration of antibodies demonstrated promising results for bone tissue engineering. However, more investigations, particularly in larger animals, are required for their further possible clinical administration.
A. Khojasteh, S. Hosseinpour, M. M. Dehghan, F. Mashhadiabbas, M. Rezai Rad, S. Ansari, S. Farzad Mohajeri, and H. H. Zadeh
BioMed Research International, ISSN: 23146133, eISSN: 23146141, Volume: 2018, Published: 2018 Hindawi Limited
Among many applications of therapeutic monoclonal antibodies (mAbs), a unique approach for regenerative medicine has entailed antibody-mediated osseous regeneration (AMOR). In an effort to identify a clinically relevant model of craniofacial defect, the present study investigated the efficacy of mAb specific for bone morphogenetic protein- (BMP-) 2 to repair canine segmental mandibular continuity defect model. Accordingly, a 15 mm unilateral segmental defect was created in mandible and fixated with a titanium plate. Anorganic bovine bone mineral with 10% collagen (ABBM-C) was functionalized with 25 μg/mL of either chimeric anti-BMP-2 mAb or isotype-matched mAb (negative control). Recombinant human (rh) BMP-2 served as positive control. Morphometric analyses were performed on computed tomography (CT) and histologic images. Bone densities within healed defect sites at 12 weeks after surgery were 1360.81 ± 10.52 Hounsfield Unit (HU), 1044.27 ± 141.16 HU, and 839.45 ± 179.41 HU, in sites with implanted anti-BMP-2 mAb, rhBMP-2, and isotype mAb groups, respectively. Osteoid bone formation in anti-BMP-2 mAb (42.99% ± 8.67) and rhBMP-2 (48.97% ± 2.96) groups was not significantly different but was higher (p<0.05) than in sites with isotype control mAb (26.8% ± 5.35). In view of the long-term objective of translational application of AMOR in humans, the results of the present study demonstrated the feasibility of AMOR in a large clinically relevant animal model.
Hanieh Nokhbatolfoghahaei, Maryam Rezai Rad, Mohammad-Mehdi Khani, Shayan Shahriari, Nasser Nadjmi, and Arash Khojasteh
Current Stem Cell Research and Therapy, ISSN: 1574888X, Pages: 564-599, Published: 1 October 2017 Bentham Science Publishers Ltd.
BACKGROUND Traditional attempts to grow bone grafts in vitro have been based on culturing cell-scaffold constructs under static culture conditions. However, limitations associated with this approach have led to the development of various types of technologies and equipments. One of these is a bioreactor acting as an intermediate between static (in vitro) and dynamic (in vivo) conditions, which can mimic physiological and mechanical body conditions. OBJECTIVE The aim of this study was to systematically review the available literature on application of different types of bioreactors in bone tissue engineering. METHODS A thorough search in PubMed and Google Scholar databases from January 2011 to December 2016 was performed. All in vitro and in vivo studies about bioreactor applications in bone tissue engineering were included and categorized according to bioreactor types. CONCLUSION A comprehensive systematic review of all the studies from the past five years yielded several findings: (1) combined bioreactors seem effective in bone tissue engineering; (2) 1- 2 ml/min is an appropriate flow rate range; (3) a cylinder is an appropriative scaffold shape; and (4) incubation of the scaffold with cells prior to transfer to the bioreactor followed by administration of osteogenic medium in the bioreactor seems an efficient approach to help cells properly attach and differentiate.
Nasim Salehi-Nik, Maryam Rezai Rad, Pantea Nazeman, and Arash Khojasteh
Biomaterials for Oral and Dental Tissue Engineering, Pages: 25-46, Published: 1 August 2017 Elsevier
Scaffolds are one of the key role players in triad of tissue engineering but one of the major challenges facing tissue engineers is creating appropriate scaffolds that resemble the structure of the desired tissue to be replaced. Among different materials used for scaffold fabrication, natural and synthetic polymers have received a great attention because of the easy control over their mechanical properties accordant to the tissue specificities, as well as ability to be produced on a large scale using reproducible methods. This chapter focuses on the different types of polymeric materials and fabrication techniques used for scaffold development, highlighting key advances in biomimetic and complex three-dimensional scaffolds.
Zahrasadat Paknejad, Maissa Jafari, Pantea Nazeman, Maryam Rezai Rad, and Arash Khojasteh
Biomaterials for Oral and Dental Tissue Engineering, Pages: 405-428, Published: 1 August 2017 Elsevier
Healthy peri-implant tissue with sufficient quality and quantity is among the determining factors of implant success and survival. Accordingly, reconstruction of deficient peri-implant tissues may be an essential treatment prior to implant insertion. Routinely, conventional techniques are implemented to meet this demand however, these techniques are associated with pitfalls such as morbidity in obtaining bone grafts or limited available sources. These limitations have led to use of other potential sources and techniques such as stem cells, growth factors, and scaffolds to further enhance bone regeneration around implants and promote the osseous integration. This chapter aims to review and challenge the conventional approaches applied in this field and will further discuss the novel methods and assumptions incorporated in peri-implant tissue regeneration.
Sepanta Hosseinpour, Mitra Ghazizadeh Ahsaie, Maryam Rezai Rad, Mohammad taghi Baghani, Saeed Reza Motamedian, and Arash Khojasteh
Oral and Maxillofacial Surgery, ISSN: 18651550, eISSN: 18651569, Pages: 109-129, Published: 1 June 2017 Springer Science and Business Media LLC
PurposeThe current systematic review investigated the results of application of some of the most commonly used scaffolds in conjugation with stem cells and growth factors in animal and clinical studies.MethodsA comprehensive electronic search was conducted according to the PRISMA guidelines in NCBI PMC and PubMed from January 1970 to December 2015 limited to English language publications with available full texts. In vivo studies in relation to “bone healing,” “bone regeneration,” and at least one of the following items were investigated: allograft, β-tricalcium phosphate, deproteinized bovine bone mineral, hydroxyapetite/tricalcium phosphate, nanohydroxyapatite, and composite scaffolds.ResultsA total of 1252 articles were reviewed, and 46 articles completely fulfilled the inclusion criteria of this study. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used. Among studies being reported in this review, bone marrow mesenchymal stem cells are the most studied mesenchymal stem cells, β-tricalcium phosphate is the most frequently used scaffold, and platelet-rich plasma is the most commonly used growth factor.ConclusionThe current review aimed to inform reconstructive surgeons of how combinations of various mesenchymal stem cells, scaffolds, and growth factors enhance bone regeneration. The highest bone regeneration has been achieved when combination of all three elements, given scaffolds, mesenchymal stem cells, and growth factors, were used.
Farshid Bastami, Pantea Nazeman, Hamidreza Moslemi, Maryam Rezai Rad, Kazem Sharifi, and Arash Khojasteh
Cell Proliferation, ISSN: 09607722, eISSN: 13652184, Published: 1 April 2017 Wiley
OBJECTIVES Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising alternative source for bone regeneration. This study aimed to systematically review the available literature on osteogenic potential of iPSCs and to discuss methods applied to enhance their osteogenic potential. METHODS AND MATERIALS A thorough search of MEDLINE database was performed from January 2006 to September 2016, limited to English-language articles. All in vitro and in vivo studies on application of iPSCs in bone regeneration were included. RESULTS The current review is organized according to the PRISMA statement. Studies were categorized according to three different approaches used for osteo-induction of iPSCs. Data are summarized and reported according to the following variables: types of study, cell sources used for iPSC generation, applied reprogramming methods, applied osteo-induction methods and treatment groups. CONCLUSION According to the articles reviewed, osteo-induced iPSCs revealed osteogenic capability equal to or superior than MSCs; cell sources do not significantly affect osteogenic potential of iPSCs; addition of resveratrol to the osteogenic medium (OM) and irradiatiation after osteogenic induction reduce teratoma formation in animal models; transfection with lentiviral bone morphogenetic protein 2 results in higher mineralization compared to osteo-induction in OM; addition of TGF-β, IGF-1 and FGF-β to OM increases osteogenic capability of iPSCs.
Farshid Bastami, Zahrasadat Paknejad, Maissa Jafari, Majid Salehi, Maryam Rezai Rad, and Arash Khojasteh
Materials Science and Engineering C, ISSN: 09284931, Pages: 481-491, Published: 1 March 2017 Elsevier BV
Fabrication of an ideal scaffold having proper composition, physical structure and able to have sustained release of growth factors still is challenging for bone tissue engineering. Current study aimed to design an appropriate three-dimensional (3-D) scaffold with suitable physical characteristics, including proper compressive strength, degradation rate, porosity, and able to sustained release of bone morphogenetic protein-2 (BMP2), for bone tissue engineering. A highly porous 3-D β-tricalcium phosphate (β-TCP) scaffolds, inside of which two perpendicular canals were created, was fabricated using foam-casting technique. Then, scaffolds were coated with gelatin layer. Next, BMP2-loaded chitosan (CS) nanoparticles were dispersed into collagen hydrogel and filled into the scaffold canals. Physical characteristics of fabricated constructs were evaluated. Moreover, the capability of given construct for bone regeneration has been evaluated in vitro in interaction with human buccal fat pad-derived stem cells (hBFPSCs). The results showed that gelatin-coated TCP scaffold with rhBMP2 delivery system not only could act as a mechanically and biologically compatible framework, but also act as an osteoinductive graft by sustained delivering of rhBMP2 in a therapeutic window for differentiation of hBFPSCs towards the osteoblast lineage. The proposed scaffold model can be suggested for delivering of cells and other growth factors such as vascular endothelial growth factor (VEGF), alone or in combination, for future investigations.
Maissa Jafari, Zahrasadat Paknejad, Maryam Rezai Rad, Saeed Reza Motamedian, Mohammad Jafar Eghbal, Nasser Nadjmi, and Arash Khojasteh
Journal of Biomedical Materials Research - Part B Applied Biomaterials, ISSN: 15524973, eISSN: 15524981, Volume: 105, Pages: 431-459, Published: 1 February 2017 Wiley
The tissue engineering scaffold acts as an extracellular matrix that interacts to the cells prior to forming new tissues. The chemical and structural characteristics of scaffolds are major concerns in fabricating of ideal three-dimensional structure for tissue engineering applications. The polymer scaffolds used for tissue engineering should possess proper architecture and mechanical properties in addition to supporting cell adhesion, proliferation, and differentiation. Much research has been done on the topic of polymeric scaffold properties such as surface topographic features (roughness and hydrophilicity) and scaffold microstructures (pore size, porosity, pore interconnectivity, and pore and fiber architectures) that influence the cell-scaffold interactions. In this review, efforts were given to evaluate the effect of both chemical and structural characteristics of scaffolds on cell behaviors such as adhesion, proliferation, migration, and differentiation. This review would provide the fundamental information which would be beneficial for scaffold design in future. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 431-459, 2017.
Maryam Rezai Rad, Mahbobeh Bohloli, Mahshid Akhavan Rahnama, Azadeh Anbarlou, Pantea Nazeman, and Arash Khojasteh
Stem Cells International, eISSN: 16879678, Volume: 2017, Published: 2017 Hindawi Limited
The advantages of adipose-derived stem cells (AdSCs) over bone marrow stem cells (BMSCs), such as being available as a medical waste and less discomfort during harvest, have made them a good alternative instead of BMSCs in tissue engineering. AdSCs from buccal fat pad (BFP), as an easily harvestable and accessible source, have gained interest to be used for bone regeneration in the maxillofacial region. Due to scarcity of data regarding comparative analysis of isolated AdSCs from different parts of the body, we aimed to quantitatively compare the proliferation and osteogenic capabilities of AdSCs from different harvesting sites. In this study, AdSCs were isolated from BFP (BFPdSCs), abdomen (abdomen-derived mesenchymal stem cells (AbdSCs)), and hip (hip-derived mesenchymal stem cells (HdSCs)) from one individual and were compared for surface marker expression, morphology, growth rate, and osteogenic differentiation capability. Among them, BFPdSCs demonstrated the highest proliferation rate with the shortest doubling time and also expressed vascular endothelial markers including CD34 and CD146. Moreover, the expression of osteogenic markers were significantly higher in BFPdSCs. The results of this study suggested that BFPdSCs as an encouraging source of mesenchymal stem cells are to be used for bone tissue engineering.
Nasim Salehi-Nik, Maryam Rezai Rad, Lida Kheiri, Pantea Nazeman, Nasser Nadjmi, and Arash Khojasteh
Stem Cells International, eISSN: 16879678, Volume: 2017, Published: 2017 Hindawi Limited
Adipose tissues hold great promise in bone tissue engineering since they are available in large quantities as a waste material. The buccal fat pad (BFP) is a specialized adipose tissue that is easy to harvest and contains a rich blood supply, and its harvesting causes low complications for patients. This review focuses on the characteristics and osteogenic capability of stem cells derived from BFP as a valuable cell source for bone tissue engineering. An electronic search was performed on all in vitro and in vivo studies that used stem cells from BFP for the purpose of bone tissue engineering from 2010 until 2016. This review was organized according to the PRISMA statement. Adipose-derived stem cells derived from BFP (BFPSCs) were compared with adipose tissues from other parts of the body (AdSCs). Moreover, the osteogenic capability of dedifferentiated fat cells (DFAT) derived from BFP (BFP-DFAT) has been reported in comparison with BFPSCs. BFP is an easily accessible source of stem cells that can be obtained via the oral cavity without injury to the external body surface. Comparing BFPSCs with AdSCs indicated similar cell yield, morphology, and multilineage differentiation. However, BFPSCs proliferate faster and are more prone to producing colonies than AdSCs.
Maryam Rezia Rad, Moein Khojaste, Mehrnoosh Hasan Shahriari, Saeed Asgary, and Arash Khojasteh
Biomedicine and Pharmacotherapy, ISSN: 07533322, eISSN: 19506007, Pages: 432-438, Published: 1 August 2016 Elsevier BV
OBJECTIVES Growth factors play a significant role in cell proliferation and differentiation during different stages of the bone repair. However, several limitations have been brought researchers attention to an osteoinductive small molecule including Purmorphamine. In this study, we aimed to evaluate the effect of Purmorphamine on adhesion, proliferation and differentiation of human dental pulp stem cells (hDPSCs) seaded on beta-tricalcium phosphate (β-TCP) granules. METHODS hDPSCs were established from extracted wisdom teeth of healthy volenteers. Cells at passage 3 were seeded on β-TCP in the presence or absence of Purmorphamine. Cell adhesion and proliferation were assessed using scanning electeron microscopy (SEM) and DNA counting assay, respectively, after 1, 3 and 5days. Then, hDPSCs seeded on β-TCP were subjected to osteogenic medium with or without Purmorphamine. After 7 and 14days osteogenic diffrentiation capability of hDPSCs were determined using real-time RT-PCR and alkaline phosphatase (ALP) activity assay. RESULTS The significant increase in amount of DNA was observed at day 3 and 5 in the presence of Purmorphamine. SEM imaging also was confirmed the DNA counting assay; in all given time points, hDPSC attachment and growth was significantly higher in the presence of Purmorphamine. ALP activity was increased by Purmorphamine at both 7 and 14days of induction. Purmorphamine showed to effect on osteopontin expression at earlier stage of osteogenic differentiation, whereas for osteocalcin expression, this effect was more evident at later stage of differentiation. CONCLUSION Purmorphamine had a promotive effect on adhesion, proliferation and osteogenic differentiation of hDPSCs cultured on β-TCP. The outcome of the current study would help in development of in vitro culture conditions for better osteogenic differentiation of hDPSCs prior to transplantation.
Arash Khojasteh, Pantea Nazeman, and MaryamRezai Rad
Dental Hypotheses, eISSN: 21558213, Pages: 56-60, Published: April-June 2016 Medknow
Introduction: One of the most common side effects of bisphosphonate intake is osteonecrosis of the jaw (ONJ) which may develop following dentoalveolar interventions. Despite the vast available protocols, there is no clear guideline in the management of this condition. In osteonecrosis, the number and proliferation of bone-forming cells as well as vascularity are disturbed. Erythropoietin (EPO) is a hematopoietic hormone with angiogenic, osteogenic, and antiapoptotic properties. The Hypothesis: It is suggested to utilize poly lactic-co-glycolic acid hydrogel containing 1500-3000 IU/kg EPO following dentoalveolar surgery in samples receiving bisphosphonates as a preventive or therapeutic agent. Evaluation of the Hypothesis: Considering the pathophysiology of ONJ and therapeutic properties of EPO, it is assumed that EPO may be effective in treatment of ONJ. Furthermore, as a preventive measure, utilizing EPO following dentoalveolar surgery may be beneficial in the patients at risk of ONJ.
Maryam Rezai Rad, Dawen Liu, Hongzhi He, Hunter Brooks, Mei Xiao, Gary E. Wise, and Shaomian Yao
Archives of Oral Biology, ISSN: 00039969, eISSN: 18791506, Pages: 546-556, Published: 26 December 2015 Elsevier BV
OBJECTIVES Primary isolated dental follicle stem cells (DFSCs) possess a strong osteogenesis capability, and such capability is reduced during in vitro culture. Because dentin matrix protein 1 (DMP1) is essential in the maturation of osteoblasts, our objectives were to determine (1) the expression of DMP1 in the DFSCs, (2) the correlation between DMP1 expression and osteogenic capability of DFSCs, and (3) the ability of DMP1 to promote osteogenic differentiation of DFSCs. METHODS DFSCs and their non-stem cell counterpart dental follicle cells (DFC) were established from postnatal rat pups. Expression of DMP1 in the DFSCs and DFC was determined using real-time RT-PCR and western blotting. Different passages of DFSCs were subjected to osteogenic induction. The correlation between osteogenesis and DMP1 expression was analyzed. Then, expression of DMP1 in the DFSCs was knocked-down using siRNA, followed by osteogenic induction to evaluate the effect of DMP1-knockdown. Finally, the late passage DFSCs with reduced DMP1 expression and osteogenic capability were cultured in osteogenic induction medium containing mouse recombinant DMP1 (mrDMP1) to determine if DMP1 can restore osteogenesis of DFSCs. RESULTS DFSCs expressed much higher levels of DMP1 than did DFC. DMP1 expression was correlated with the osteogenic capability of DFSCs. Knockdown of DMP1 expression markedly decreased the osteogenesis and osteogenic gene expression in the DFSCs whereas adding mrDMP1 protein to the osteogenic induction medium enhanced osteogenesis. CONCLUSIONS DMP1 is highly expressed in the DFSCs, but minimally expressed in non-stem cell DFC. DMP1 appears to play an important role for osteogenic differentiation of the DFSCs.
Maryam Rezai-Rad, Jonathan F. Bova, Mahdi Orooji, Jennifer Pepping, Ammar Qureshi, Fabio Del Piero, Daniel Hayes, and Shaomian Yao
Cytotherapy, ISSN: 14653249, eISSN: 14772566, Pages: 1572-1581, Published: 1 November 2015 Elsevier BV
BACKGROUND AIMS Stem cell-based tissue regeneration offers potential for treatment of craniofacial bone defects. The dental follicle, a loose connective tissue surrounding the unerupted tooth, has been shown to contain progenitor/stem cells. Dental follicle stem cells (DFSCs) have strong osteogenesis capability, which makes them suitable for repairing skeletal defects. The objective of this study was to evaluate bone regeneration capability of DFSCs loaded into polycaprolactone (PCL) scaffold for treatment of craniofacial defects. METHODS DFSCs were isolated from the first mandibular molars of postnatal Sprague-Dawley rats and seeded into the PCL scaffold. Cell attachment and cell viability on the scaffold were examined with the use of scanning electron microscopy and alamar blue reduction assay. For in vivo transplantation, critical-size defects were created on the skulls of 5-month-old immunocompetent rats, and the cell-scaffold constructs were transplanted into the defects. RESULTS Skulls were collected at 4 and 8 weeks after transplantation, and bone regeneration in the defects was evaluated with the use of micro-computed tomography and histological analysis. Scanning electron microscopy and Alamar blue assay demonstrated attachment and proliferation of DFSCs in the PCL scaffold. Bone regeneration was observed in the defects treated with DFSC transplantation but not in the controls without DFSC transplant. Transplanting DFSC-PCL with or without osteogenic induction before transplantation achieved approximately 50% bone regeneration at 8 weeks. Formation of woven bone was observed in the DFSC-PCL treatment group. Similar results were seen when osteogenic-induced DFSC-PCL was transplanted to the critical-size defects. CONCLUSIONS This study demonstrated that transplantation of DFSCs seeded into PCL scaffolds can be used to repair craniofacial defects.
Shaomian Yao, Hongzhi He, Dina L. Gutierrez, Maryam Rezai Rad, Dawen Liu, Chunhong Li, Michael Flanagan, and Gary E. Wise
Cells Tissues Organs, ISSN: 14226405, eISSN: 14226421, Volume: 198, Pages: 438-447, Published: 16 April 2013 S. Karger AG
The dental follicle (DF) plays an essential role in tooth eruption via regulation of bone resorption and bone formation. Bone morphogenetic protein-6 (BMP6) expression in the DF is coincident with bone growth in the tooth crypt. DF stem cells (DFSCs) have been shown to possess strong osteogenic capability. This study aims to determine the expression of BMP6 in DFSCs and to elucidate the role of BMP6 in the osteogenesis of DFSCs. DFSCs and their non-stem cell counterpart, DF cells (DFCs), were obtained from the DFs of rat pups. We showed that expression of BMP6 was significantly higher in the DFSCs than in the DFCs. DFSCs lost osteogenic capability during in vitro expansion, and DFSCs in late passages had reduced BMP6 expression as compared to early passages of DFSCs when they were subjected to osteogenic induction. Addition of exogenous human recombinant BMP6 (hrBMP6) to the osteogenic medium dramatically enhanced the osteogenesis of the late-passage DFSCs. Knockdown of BMP6 by short interfering RNA in the DFSCs in early passages resulted in a decrease in osteogenesis, which could be restored by addition of hrBMP6. We concluded that DFSCs need to express high levels of BMP6 to maintain their osteogenesis capability. Increased BMP6 expression seen in vivo in the DF may reflect the activation of DFSCs for osteogenic differentiation for bone growth during tooth eruption.
M. Rezai Rad, G.E. Wise, H. Brooks, M.B. Flanagan, and S. Yao
Cell Proliferation, ISSN: 09607722, eISSN: 13652184, Pages: 58-66, Published: February 2013 Wiley
OBJECTIVES Adult stem cells (ASCs) remain in a slowly cycling/quiescent state under normal physiological conditions, but they can be awakened from this by certain factors, such as injury signals. Previously, our group has shown that dental follicle stem cells (DFSCs) appear to proliferate more rapidly than their non-stem cell counterparts at elevated temperatures. The study described here has aimed to (i) elucidate optimal temperature in which to culture DFSCs, (ii) determine whether elevated temperatures could enhance differentiation capability of DFSCs and (iii) characterize stem cell and osteogenic marker expression of DFSCs at elevated temperatures. MATERIALS AND METHODS DFSCs obtained from rat first molars were cultured at 37 (control), 38, 39, 40 and 41 ºC. Cell proliferation was evaluated by Alamar blue reduction assay and mean numbers of viable dissociated cells. Osteogenic differentiation was evaluated after 7 or 14 days osteogenic induction. Expression of selected marker genes was also assessed during proliferation and differentiation of the cells. RESULTS Increased cell proliferation was seen at heat-stress temperatures of 38º, 39º and 40 ºC. DFSCs revealed maximal osteogenesis when cultured at 39 and 40 ºC. Moreover, some stem cell and osteogensis-associated markers had elevated expression in heat-stress conditions. CONCLUSIONS Under determined heat-stress conditions, DFSCs increased their proliferation, osteogenic differentiation and expression of some marker genes. Thus, it is likely that elevated temperature could serve as a factor to activate adult stem cells.