Maryam Soleimani, Seyed Behnamedin Jameie, Mahmood Barati, Mehdi Mehdizadeh, Mahdieh Erdari,
Volume 18, Issue 4 (10-2014)
Abstract
Background: Multiple sclerosis (MS) is known as a progressive central nervous system inflammatory disease. Certain factors, such as interleukins, inflammatory cells, and oxidative stress are supposed to involve in MS etiology. Because of the important role of oxidative stress, antioxidant therapy for MS has received more attention. Although coenzyme Q10 (CoQ10) acts as an antioxidant, there is a lack of enough research on its effects on MS. Therefore, the present research was designed. Methods: C57BL/6 female adult mice (n = 30) were used in this study. The animals were randomly divided into trial and control groups. To induce MS, routine procedure for experimental autoimmune encephalomyelitis (EAE) was used, and scoring was performed based on clinical signs. By detecting score one, CoQ10 administration was started (10 mg/kg/three weeks). By using ELISA and real-time PCR, the brain levels of TNF-gamma, IL-10, IL-4, and IL-12 were studied. Statistical tests were used to analyze the data and the P value less than 0.05 was considered to be significant. Results: Clinical symptoms in EAE animals were significantly decreased (P<0.05) as compared to control ones. In addition, the level of the TNF-gamma was significantly decreased following CoQ10 administration versus IL-10. The ratio of TH1/TH2 interleukins in treated animals was significantly less than that in non-treated animals (P<0.01). Conclusion: Our findings showed that CoQ10 is capable of suppressing the inflammatory pathway of MS.
Niloofar Sefati, Mohsen Norouzian, Hojjat-Allah Abbaszadeh, Mohammad-Amin Abdollahifar, Abdollah Amini, Mohammad Bagheri, Arefeh Aryan, Fatemeh Fadaei Fathabady,
Volume 22, Issue 2 (3-2018)
Abstract
Background: Hypothyroidism is associated with dysfunction of the bone turnover with reduced osteoblastic bone formation and osteoclastic bone resorption. Mesenchymal stem cells (MSCs) secrete various factors and cytokines that may stimulate bone regeneration. The aim of this study was to determine the effects of MSCs-conditioned medium (CM) in hypothyroidism male rats after inducing bone defect. Methods: In this study, 24 male rats were randomly assigned to three groups: (I) hypothyroidism + bone defect (HYPO), (II) hypothyroidism + bone defect + CM (HYPO + CM), and (III) no hypothyroidism + bone defect (control). Four weeks after surgery, the right tibia was removed, and immediately, biomechanical and histological examinations were performed. Results: The results showed a significant reduction in bending stiffness (32.64 ± 3.99), maximum force (14.63 ± 1.89), high stress load (7.59 ± 2.31), and energy absorption (12.68 ± 2.12) at the osteotomy site in hypothyroidism rats in comparison to the control and hypothyroidism + condition medium groups (p < 0.05). There was also a significant decrease in the trabecular bone volume (3.86 ± 3.88) and the number of osteocytes (5800 ± 859.8) at the osteotomy site in hypothyroidism rats compared to the control and hypothyroidism + condition medium groups (p < 0.01 and p < 0.02, respectively). Conclusion: The present study suggests that the use of the CM can improve the
fracture regeneration and accelerates bone healing at the osteotomy site in hypothyroidism rats.
Hojjat Allah Abbaszadeh, Taki Tiraihi, Yousef Sadeghi, Ali Reza Delshad, Majid Sadeghizadeh, Taher Taheri, Ali Noori-Zadeh,
Volume 22, Issue 4 (7-2018)
Abstract
Background: Oligodendrocyte cell death is among the important features of spinal cord injury, which appears within 15 min and occurs intensely for 4 h after injury, in the rat spinal contusion model. Accordingly, the number of oligodendrocytes progressively reduced within 24 h after injury. Administration of oligodendrocyte-like cells (OLCs) into the lesion area is one of the approaches to counterbalance this condition. Methods: Bone marrow stromal cells were transdifferentiated into neurospheres and then into neural stem cells and later were differentiated into OLCs using triiodothyronine and transplanted into the spinal cord contusion rats. The post-injury functional recovery was explored and compared with the control group using Basso-Beattie-Bresnahan and narrow beam behavioral tests. At the end of 12th week, spinal cord segments T12-L1 were histomorphologically studied by immunohistochemistry. Results: Motor improvement was more obvious during 2nd to 4th weeks and got less prominent during 4th to 12th weeks. Histomorphometric findings indicated that cavity formation decreased in epicenter of transplantation area in experimental groups in comparison with the control groups. Conclusion: The findings obtained in the present study showed that OLC therapy is a potential approach in the treatment of spinal cord traumatic injuries.
Ahmad Alrahel, Mansoureh Movahedin, Zohre Mazaheri, Fardin Amidi,
Volume 22, Issue 4 (7-2018)
Abstract
Background: In vitro spermatogenesis has a long research history beginning in the early 20th century. This organ culture method was therefore abandoned, and alternative cell culture methods were chosen by many researchers. Here, whether Tnp1, Tekt1, and Plzf, which play a crucial role in spermatogenesis, can be expressed during testis organ culture was assessed. Methods: Testes of 10 mouse pups were first removed, and the testis tissue was then separated into smaller pieces of seminiferous tubules. The size of the pieces was arbitrary; approximately 1 mg in weight or 1 mm3 in size when compacted. Afterwards, the testis tissue fragments (1–3) were transferred to the hexahedrons, incubated in a culture incubator and cultured for 12 weeks. Histological assessment and molecular evaluation were carried out at the end of the study. Results: The results showed that the expression of Tekt1 as a mitotic gene in mouse pups decreased significantly (p ≤ 0.05) in comparison to adult mouse testis. Meanwhile, the expression of Tnp1 as a meiotic gene increased significantly (p ≤ 0.05) as compared to neonate mouse testis at the beginning of the culture. The expression of Plzf showed no significant difference during the 12 weeks of culture (p ≥ 0.05). Based on histological study, different types of spermatocytes and post-meiotic stages of germ cells could not be detected. Conclusion: This kind of three-dimensional culture can induce expression of post-meiotic gene, Tnp1, but only at the molecular level and not beyond meiosis.
Mohsen Marzban, Kazem Mousavizadeh, Masoomeh Bakhshayesh, Nasim Vousooghi, Gelareh Vakilzadeh, Anahita Torkaman-Boutorabi,
Volume 22, Issue 5 (9-2018)
Abstract
Background: Bone marrow mesenchymal stem cells (BM-MSCs) elicit neuroprotective effects, and their repair ability has been investigated in different experimental models. We aimed to investigate the effect of multiple i.p. BM-MSCs injections in the cuprizone model of multiple sclerosis in mice. Methods: Adult male C57BL/6 mice (n = 40) were fed a regular diet or a diet containing cuprizone (0.2% w/w) for 6 six weeks. Bone marrow samples were taken from patients with spinal cord injury. BM-MSCs (2 × 106 in 1 milliliter medium) were administered intraperitoneally for two consecutive weeks at the end of the forth weeks of cuprizone administration. Animals (n = 12) were perfused with 10% paraformaldehyde at the end of sixth week. The brains were sectioned coronally in 6-8-μm thickness (-2.3 to 1.8 mm from bregma). The sections were stained by luxol fast blue-cresyl violet, and images were captured via a microscope. Demyelination ratio was estimated in corpus callosum in a blind manner. A quantitative real-time PCR was used to measure the myelin basic protein gene expression at sixth week. Results: Histologically, cuprizone induced demyelination in the corpus callosum. Demyelinated area was diminished in the corpus callosum of cell-administered group. Cuprizone could decrease myelin-binding protein mRNAs expression in corpus callosum, which was significantly recovered after BM-MSCs injections. Conclusion: Our data indicated a remyelination potency of multiple i.p. BM-MSCs in the cuprizone model of multiple sclerosis in mice.
Farzaneh Chehelcheraghi, Abolfazl Abbaszadeh, Magid Tavafi,
Volume 22, Issue 5 (9-2018)
Abstract
Background: Skin flap procedures are employed in plastic surgery, but failure can lead to necrosis of the flap. Studies have used bone marrow mesenchymal stem cells (BM-MSCs) to improve flap viability. BM-MSCs and acellular amniotic membrane (AAM) have been introduced as alternatives. The objective of this study was to evaluate the effect of BM-MSCs and AAM on mast cells of random skin flaps (RSF) in rats. Methods: RSFs (80 × 30 mm) were created on 40 rats that were randomly assigned to one of four groups, including (I) AAM, (II) BM-MSCs, (III) BM-MSCs/AAM, and (IV) saline (control). Transplantation was carried out during the procedure (zero day). Flap necrosis was observed on day 7, and skin samples were collected from the transition line of the flap to evaluate the total number and types of mast cells. The development and the total number of mast cells were related to the development of capillaries. Results: The results of one-way ANOVA indicated that there was no statistically significant difference between the mean numbers of mast cell types for different study groups. However, the difference between the total number of mast cells in the study groups was statistically significant (p = 0.001). Conclusion: The present study suggests that the use of AAM/BM-MSCs can improve the total number of mast cells and accelerate the growth of capillaries at the transient site in RSFs in rats.
Shirin Farivar, Fateme Shaabanpour Aghamaleki,
Volume 22, Issue 5 (9-2018)
Abstract
The pathogenesis of systemic lupus erythematosus (SLE) is influenced by both genetic factors and epigenetic modifications; the latter is a result of exposure to various environmental factors. Epigenetic modifications affect gene expression and alter cellular functions without modifying the genomic sequences. CpG-DNA methylation, histone modifications, and miRNAs are the main epigenetic factors of gene regulation. In SLE, global and gene-specific DNA methylation changes have been demonstrated to occur in CD4+ T-cells. Moreover, histone acetylation and deacetylation inhibitors reverse the expression of multiple genes involved in SLE, indicating histone modification in SLE. Autoreactive T-cells and B-cells have been shown to alter the patterns of epigenetic changes in SLE patients. Understanding the molecular mechanisms involved in the pathogenesis of SLE is critical for the introduction of effective, target-directed and tolerated therapies. In this review, we summarize the recent findings that highlight the importance of epigenetic modifications and their mechanisms in SLE.
Pawan Kumar, Brijnandan S. Dehiya, Anil Sindhu,
Volume 23, Issue 3 (5-2019)
Abstract
Background: This study addressed the development of biodegradable and biocompatible scaffolds with enhanced biomechanical characteristics. The biocompatibility and the cationic nature of chitosan (CTS) make it more effective as a bone grafting material. Methods: The hydroxyapatite nanoparticles (nHA) were synthesized by hydrothermal method, and bioglass (nBG) (50% SiO2-45% CaO-5% P2O5) was synthesized using sol-gel method. The ibuprofen-loaded CTS/nHA and CTS/nBG scaffolds were fabricated by using freeze-drying method. Results: Transmission electron microscopy image of nHA and nBG revealed the particles of less than 200 nm. The scanning electron microscopy (SEM) images of CTS/nHA and CTS/nBG scaffolds showed pore sizes ranging from 84-190 µm. The physiochemical characteristics of synthesized ceramic nanoparticles and scaffolds analyzed by XRD were confirmed by ICDD 9-432. The porosity of scaffolds was measured by using SEM, Brunauer-Emmett-Teller method and Archimedes’ principle. The open porosities of CTS/nBG and CTS/nHA samples were 29% and 31%, respectively. The compressive strength of scaffolds was evaluated by stress vs. strain curve. The CTS/nHA scaffold revealed 4% more water retention capacity than CTS/nBG scaffold. In the presence of lysozyme, CTS/nBG scaffold degraded 32.8%, while CTS/nHA degraded 26.1% in PBS solution at pH 7.4. The density of all scaffolds was found (1.9824 g/cm-3 and 1.9338 g/cm-3) to be nearly similar to that of the dry bone (0.8-1.2 g/cm-3). Fibroblast cells multiplied two times in the sample medium of CTS/nBG after 14 days. After 72 h, CTS/nBG and CTS/nHA scaffolds demonstrated 52% and 46% drug release, respectively. Conclusion: Based on our findings, ibuprofen-loaded scaffolds could be an effective drug delivery system for tissue engineering applications.
Azar Babakhani, Paria Hashemi, Javad Mohajer Ansari, Parisa Ramhormozi, Malihe Nobakht,
Volume 23, Issue 6 (11-2019)
Abstract
Background: Hair follicle stem cells (HFSCs) located in the bulge area has shown to be highly proliferative and could differentiate into neurons, glia, smooth muscle cell, and melanocytes in vitro. Simvastatin is an HMG-CoA reductase inhibitor that exerts pleiotropic effects beyond simple low-density lipoprotein lowering and has a similar impact on the differentiation of bone marrow stromal cells and peripheral blood mononuclear cells. The present study examined the hypothesis that the application of simvastatin would induce the HFSCs differentiation into keratinocyte. Methods: The bulge of the hair follicle was anatomized, and HFSCs were cultivated. The flow cytometry and immunocytochemical staining for detection of nestin, CD34, and Kr15 biomarkers were performed before differentiation. In order to hasten the HFSCs differentiation to keratinocyte, HFSCs were treated with 1 µM, 2 µM, and 5 µM of simvastatin daily for a week. After differentiation, the flow cytometry and immunocytochemical staining were performed with Kr15 and Kr10 biomarkers, and the MTT assay was carried out as an index of cell viability and cell growth. Results: Our results showed that bulge of HFSCs were nestin and CD34 positive and Kr15 negative. Simvastatin significantly increased the viability of HFSCs (p < 0.05) at the concentration of 5 µM. In addition, the percentages of keratinocyte-differentiated cells treated with 5 µM of simvastatin showed a significant increase compared to all other treated groups (p < 0.05). Conclusion: Our findings demonstrate that 5 µM of simvastatin could induce HFSCs differentiation into keratinocyte.
Soghra Bahmanpour, Amirhesam Keshavarz , Nehleh Zarei Fard,
Volume 24, Issue 1 (1-2020)
Abstract
Background: Germ cell development processes are influenced by soluble factors and intercellular signaling events between them and the neighboring somatic cells. More insight into the molecular biology of the germ cell development from embryonic stem (ES) cells and investigation of appropriate factors, specifically those targeting differentiation processes, is of great importance. In this study, we established an in vitro model with higher ES cell differentiation rate to germ cells, using adenylate cyclase activator, forskolin. Methods: ES cells were first cultured for five days, leading to embryoid body (EB) formation. Subsequently, the EB were dissociated and cultured for an additional three days in different forskolin concentrations of 5, 20, and 50 µM, with or without granulosa cells (GC) co-culture. On the 8th day, we analyzed the expressions of 5 germ cell-specific markers using quantitative real-time-PCR technique along with cell viability assay by MTT test. Results: Our results showed that in the GC-free cultures, a 50-µM concentration of forskolin resulted in a significant increase in Mvh, Gdf9, Scp3, and Rec8 expression levels in comparison to the control. However, when the cells were co-cultured with the GCs, 20-µM concentration of forskolin could also increase the expression of those germ cell-specific marker genes. Furthermore, results from the MTT assay showed enhanced cell proliferation and survival at all three concentrations of forskolin, but 20-µM concentration was the most potent one. Conclusion: These data indicate that forskolin can stimulate differentiation and proliferation, dose-dependently; however, the influence of GCs co-culturing should not go unnoticed.
Azar Babakhani, Malihe Nobakht, Hamidreza Pazoki Torodi, Mostafa Dahmardehei, Paria Hashemi, Javad Mohajer Ansari, Parisa Ramhormozi, Abazar Yari, Fatemeh Heidari,
Volume 24, Issue 2 (3-2020)
Abstract
Background: The recent improvements in wound healing have led to new strategies in regenerative medicine. Burn wound healing is an important issue in skin regeneration and has multiple indications for stem cell therapy. Hair follicle stem cells (HFSCs) are a highly promising source of stem cells for healing use, as these cells are accessible, active and pluripotent adult stem cells. Methods: HFSCs of the rat whisker were isolated, cultured, and labeled with DiI. Flow cytometry method was used to detect special markers of HFSCs. Deep partial-thickness burn wound was created, and labeled HFSCs were injected around the wound bed. Wound closure was recorded via digital photographs. The inflicted rats were sacrificed at 3, 7, or 14 days post burn and used for subsequent histological and tensiometry analysis. Results: Our results indicated that HFSCs were positive for Nestin and CD34 markers, but negative for Kr15. Morphological and histological photographs revealed that wound closure rate was accelerated in stem cell-treated group compared with other groups. In addition, faster re-epithelialization and collagen deposition were observed. The immunohistochemical analysis suggested that CD31 expression and vascular density enhanced in the stem cell-treated group. Further, tissue tensile strength increased in HFSCs-treated rats in comparison to the control group. Conclusion: The present study demonstrates that HFSC could accelerate burn wound healing as well as tensile strength in rats.
Mansooreh-Sadat Seyedkarimi, Hamid Mirzadeh, Aliasghar Mohammadi, Shadab Bagheri-Khoulenjani,
Volume 24, Issue 2 (3-2020)
Abstract
Background: Self-assembling peptides (SApeptides) have growing applications in tissue engineering and regenerative medicine. The application of SApeptide-based hydrogels depends strongly on their viscoelastic properties. Optimizing the properties is of importance in tuning the characteristics of the hydrogels for a variety of applications. Methods: In this study, we employed statistical modeling, conducted with the response surface methodology (RSM) and particle tracking microrheology, to investigate the effects of self-assembling SPG-178 peptide and added NaCl salt concentrations and milieu type (deionized water or blood serum) on the viscoelastic properties of SPG-178 hydrogels. A central composite RSM model was employed for finding the optimum value of the parameters to achieve the highest storage modulus and the lowest tan δ. Results: Viscoelastic properties of each sample, including storage modulus, loss modulus, and tan δ, were determined. Storage modulus and tan δ were modeled, accounting for the impact of the SPG-178 peptide and NaCl concentrations and milieu type on the viscoelastic properties. It was found that the SPG-178 hydrogel storage modulus was positively influenced by the SPG-178 peptide concentration and the serum. Conclusion: A combination of microrheology and RSM is a useful test method for statistical modeling and analysis of rheological behavior of solid-like gels, which could be applied in various biomedical applications such as hemostasis.
Atena Shapourzadeh, Seyed Mohammad Atyabi, Shiva Irani, Hadi Bakhshi,
Volume 24, Issue 4 (7-2020)
Abstract
Background: Through combining two synthetic and natural polymers, scaffolds can be developed for tissue engineering and regenerative medicine purposes. Methods: In this work, carboxymethyl chitosan (CMC; 20%) was grafted to Polycaprolactone (PCL) nanofibers using the cold atmospheric plasma of helium. The PCL scaffolds were exposed to CAP, and functional groups were developed on the PCL surface. Results: The results of Fourier Transform Infrared Spectroscopy confirmed CMC (20%) graft on PCL scaffold. The Thiazolyl blue tetrazolium bromide assay showed a significant enhancement (p < 0.05) in the cell affinity and proliferation of adipose-derived stem cells (ADSCs) to CMC20%-graft-PCL scaffolds. After 14 days, bone differentiation was affirmed through alizarin red and calcium depositions. Conclusion: Based on the results, the CMC20%-graft-PCL can support the proliferation of ADSCs and induce the differentiation into bone with longer culture time.
Yasaman Zamani, Ghassem Amoabediny, Javad Mohammadi, Behrouz Zandieh-Doulabi, Jenneke Klein-Nulend, Marco N. Helder,
Volume 25, Issue 2 (3-2021)
Abstract
Background: One of the main challenges with conventional scaffold fabrication methods is the inability to control scaffold architecture. Recently, scaffolds with controlled shape and architecture have been fabricated using three-dimensional printing (3DP). Herein, we aimed to determine whether the much tighter control of microstructure of 3DP poly(lactic-co-glycolic) acid/β-tricalcium phosphate (PLGA/β-TCP) scaffolds is more effective in promoting osteogenesis than porous scaffolds produced by solvent casting/porogen leaching. Methods: Physical and mechanical properties of porous and 3DP scaffolds were studied. The response of pre-osteoblasts to the scaffolds was analyzed after 14 days. Results: The 3DP scaffolds had a smoother surface (Ra: 22 ± 3 µm) relative to the highly rough surface of porous scaffolds (Ra: 110 ± 15 µm). Water contact angle was 112 ± 4° on porous and 76 ± 6° on 3DP scaffolds. Porous and 3DP scaffolds had the pore size of 408 ± 90 and 315 ± 17 µm and porosity of 85 ± 5% and 39 ± 7%, respectively. Compressive strength of 3DP scaffolds (4.0 ± 0.3 MPa) was higher than porous scaffolds (1.7 ± 0.2 MPa). Collagenous matrix deposition was similar on both scaffolds. Cells proliferated from day 1 to day 14 by fourfold in porous and by 3.8-fold in 3DP scaffolds. Alkaline phosphatase (ALP) activity was 21-fold higher in 3DP scaffolds than porous scaffolds. Conclusion: The 3DP scaffolds show enhanced mechanical properties and ALP activity compared to porous scaffolds in vitro, suggesting that 3DP PLGA/β-TCP scaffolds are possibly more favorable for bone formation.
Mahdieh Javidpou, Seyed-Morteza Seifati, Ehsan Farashahi-Yazd, Fatemeh Hajizadeh-Tafti, Jalal Golzadeh, Fatemeh Akyash, Behrouz Aflatoonian,
Volume 25, Issue 2 (3-2021)
Abstract
Background: Human embryonic stem cell-mesenchymal stem/stromal cell (hESCs-MSCs) open a new insight into future cell therapy applications, due to their unique characteristics, including immunomodulatory features, proliferation, and differentiation. Methods: Herein, hESCs-MSCs were characterized by immunofluorescence technique with CD105 and FIBRONECTIN as markers and FIBRONECTIN, VIMENTIN, CD10, CD105, and CD14 genes using reverse transcription-polymerase chain reaction technique. Fluorescence-activated cell sorting was performed for CD44, CD73, CD90, and CD105 markers. Moreover, these fibroblast-like cells, due to multipotent characteristics, differentiated to the osteoblast. Results: MSCs were derived from diploid and triploid hESC lines using sequential three dimensional and two dimensional cultures and characterized with the specific markers. Immunofluorescence showed the expression of FIBRONECTIN and CD105 in hESCs-MSCs. Flow cytometry data indicated no significant difference in the expression of MSC markers after 6 and 13 passages. Interestingly, gene expression profiles revealed slight differences between MSCs from diploid and triploid hESCs. hESCs-MSCs displayed osteogenic differentiation capacity, which was confirmed by Alizarin red staining. Conclusion: Our findings reveal that both diploid and triploid hESC lines are capable of forming MSCs; however, there are some differences in their gene expression profiles. Generation of MSCs from hESCs, as a non-invasive procedure in large scale, will lend itself for the future cell-based therapeutic applications.
Mohsen Sedighi, Tourandokht Baluchnejadmojarad, Mehrdad Roghani,
Volume 25, Issue 5 (9-2021)
Abstract
Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggregate of amyloid-β (Aβ) and phosphorylated tau protein. Oxidative stress and neuroinflammation, because of Aβ peptides, are strongly involved in the pathophysiology of Alzheimer’s disease (AD). Linagliptin shows neuroprotective properties against AD pathological processes through alleviation of neural inflammation and AMPK activation. Methods: We assessed the benefits of linagliptin pretreatment (at 10, 20, and 50 nM concentrations), against Aβ1-42 toxicity (20 μM) in SH-SY5Y cells. The concentrations of secreted cytokines, such as TNF-α, IL-6, and IL-1β, and signaling proteins, including pCREB, Wnt1, and PKCε, were quantified by ELISA. Results: We observed that Aβ led to cellular inflammation, which was assessed by measuring inflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, Aβ1-42 treatment impaired pCREB, PKCε, and Wnt1 signaling in human SH-SY5Y neuroblastoma cells. Addition of Linagliptin significantly reduced IL-6 levels in the lysates of cells, treated with Aβ1-42. Furthermore, linagliptin prevented the downregulation of Wnt1 in Aβ1-42-treated cells exposed. Conclusion: The current findings reveal that linagliptin alleviates Aβ1-42-induced inflammation in SH-SY5Y cells, probably through the suppression of IL-6 release, and some of its benefits are mediated through the activation of the Wnt1 signaling pathway.
Maryam Habibi, Farzaneh Chehelcheraghii,
Volume 25, Issue 5 (9-2021)
Abstract
Background: Treatment with bone marrow mesenchymal stem cell (BMMSCs) has anti-inflammatory, tissue regenerative, angiogenic, and immune-stimulating effects. When using as sheets or accumulate, BMMSCs causes the development of neoangiogenesis in damaged skin tissue. Diabetes, a metabolic disorder, can negatively affect many physiological functions, including the process of skin injury repair. This adverse impact may increase the risk of skin surgery. Random skin flap (RSF) is commonly used in reconstructive surgery. The terminal part of the RSF is often affected by necrosis because of impaired blood flow, which is exacerbated in diabetes. This study investigated the effect of stem cells, applied as accumulated or cell sheets, along with RSF surgery on skin capillaries in streptozotocin (STZ)-induced diabetic rats. Methods: Thirty male Wistar rats were divided into three groups (n = 10): diabetes-RSF control, diabetes-RSF local applied stem cells (loc-BMMSCs), diabetes-RSF applied stem cells as accumulated or cell sheets (ac-BMMSCs). Two weeks after the STZ injection, RSF surgery and stem cell therapy (6 × 109) were carried out (day zero). Furthermore, stereological methods were used to investigate the capillary patterns among the groups. Anti-CD31/platelet endothelial cell adhesion molecule-1 immunohistochemistry was also used for further confirmation of changes in capillary parameters. Results: The results demonstrated that capillaries were protected by MSC sheets in the flap tissue, and the thickness of the epidermal layer was improved, indicationg the possible beneficial effects of MSC sheets on diabetic wound treatment. Conclusion: Stem cells, as ac-BMMSCs, may decrease the levels of wound healing complications in diabetes and can be considered as a cell therapy option in such conditions.
Neda Aboudzadeh, Alireza Khavandi, Jafar Javadpour, Mohammad Ali Shokrgozar, Mohammad Imani,
Volume 25, Issue 6 (11-2021)
Abstract
Background: Solvent casting/particulate leaching is one of the most conventional methods for fabricating polymer/ceramic composite scaffolds. In this method, the solvent generally affects resulting scaffold properties, including porosity and degradation rate. Methods: Herein, composite scaffolds of PLGA (poly(lactide-co-glycolide))/ nano-hydroxyapatite (nHA) with different percentages of nHA (25, 35, and 45 wt. %) were prepared by the solvent casting/particle leaching combined with freeze drying. The effects of two different solvents, 1,4-dioxane (DIO) and N-methyl-2-pyrrolidone (NMP), on morphology, porosity, bioactivity, degradation rate, and biocompatibility of the resulting scaffolds were investigated. Results: The results revealed that increasing the nano-hydroxyapatite (nHA) percentages had no significant effect on the porosity and interconectivity of scaffolds (p > 0.05), whereas altering the solvent from DIO into NMP decreased the porosity from about 87% into 71%, respectively. Moreover, scaffolds of DIO illustrated the high results of cell proliferation compared to those of NMP; the cell viability of GD25 decreased from 85% to 65% for GN25. The findings also indicated that scaffolds prepared by NMP had a higher rate of losing weight in comparison to DIO. Adding nHA to PLGA had a significant effect on the bioactivity of scaffolds (p < 0.05), composite scaffolds with 45 wt % nHA had at least 30% more weight gain compared to the neat polymer scaffolds. Conclusion: The DIO scaffolds have higher rates of porosity, interconnectivity, bioactivity, and biocompatibility than NMP scaffolds due to its high evaporation rate.
Fatemeh Mottaghitalab, Hamidreza Motasadizadeh, Mohammad Ali Shokrgozar, Shahrokh Shojaei, Mehdi Farokhi*,
Volume 26, Issue 2 (3-2022)
Abstract
Background: In the present study, a tissue engineered silk fibroin (SF) scaffold containing simvastatin-loaded silk fibroin nanoparticles (SFNPs) were used to stimulate the regeneration of the defected bone.
Methods: At first, the porous SF scaffold was prepared using freeze-drying. Then simvastatin-loaded SFNPs were made by dissolvation method and embedded in the SF scaffold. Afterwards, the scaffold and the NPs were characterized in terms of physicochemical properties and the ability to release the simvastatin small molecule.
Results: The results exhibited that the SF scaffold had a porous structure suitable for releasing the small molecule and inducing the proliferation and attachment of osteoblast cells. SFNPs containing simvastatin had spherical morphology and were 174 ± 4 nm in size with -24.5 zeta potential. Simvastatin was also successfully encapsulated within the SFNPs with 68% encapsulation efficiency. Moreover, the small molecule revealed a sustained release profile from the NPs during 35 days. The results obtained from the in vitro cell-based studies indicated that simvastatin-loaded SFNPs embedded in the scaffold had acceptable capacity to promote the proliferation and alkaline phosphatase production of osteoblast cells while inducing osteogenic matrix precipitation.
Conclusion: The SF scaffold containing simvastatin-loaded SFNPs could have a good potential to be used as a bone tissue-engineered construct.
Esmeralda Zuñiga, Odin Ramírez, Carlos Martínez,
Volume 26, Issue 3 (5-2022)
Abstract
Background: Biomaterials used as cell growth stimulants should be able to provide adequate cell adhesion with no alteration in cell function. In this work, we developed a three-dimensional model of mouse spinal cord motoneurons on scaffolds composed of electrospun poly-lactic acid (PLA) fibers and plasma-polymerized polypyrrole (PPy)-coated PLA fibers.
Methods: The functionality of the cultured motoneurons was assessed by evaluating both the electrophysiological response (i.e., the whole-cell Na+ and K+ currents and the firing of action potentials) and also the expression of the vesicular acetylcholine transporter (VAChaT) by immunostaining techniques. While the expression of the VAChaT was confirmed on motoneurons cultured on the fibrous scaffolds, the electrophysiological responses indicated Na+ and K+ currents with lower amplitude and slower action potentials when compared to the response recorded from spinal cord motoneurons cultured on Poly-DL-Ornithine/Laminin- and plasma-polymerized PPy-coated coverslips.
Results: From a morphological viewpoint, motoneurons cultured on PLA and PPy-coated PLA scaffolds did not show the development of dendritic and/or axonal processes, which were satisfactorily observed in the bidimensional cultures.
Conclusion: We hypothesize that the apparently limited development of dendritic and/or axonal processes could produce a deleterious effect on the electrophysiological response of the cells, which might be due to the limited growth surface available in the fibrous scaffolds and/or to an undesired effect of the purification process.