Mesenchymal Stem Cells in Regenerative Medicine, Possible Applications in The Restoration of Spermatogenesis: A Review.

Infertility is a common clinical condition and about half of the major causes are due to male-related infertility. Pathogenesis of this abnormality is generally undefined; so establishing a proper treatment option is relatively uncertain. In recent years, several evidences demonstrated that mesenchymal stem cells (MSCs) can be a hope for innovative and efficient treatment of male infertility. This study reviews possible applications of MSCs in the restoration of spermatogenesis in male infertility of both humans and animals to suggest new avenues for future clinical practices. Articles published in "PubMed" and "Google Scholar" from January 1, 2000, to August 1, 2023, were investigated by searching items of "mesenchymal stem cells", "cell therapy", "cell transplantation", and, "regenerative medicine" keywords, in addition to the "urology", "andrology", "reproductive medicine", "male infertility", "azoospermia", and "spermatogenesis". The results obtained from the transplantation of MSCs in the treatment of male infertility seemed encouraging and they revealed the safety and efficacy of these cells to recover spermatogenesis; eventhough further stem cell research is still required before recruiting clinical application of MSCs in the treatment of human male infertility. Undertaking more well-defined, standardized, and reproducible protocols and enrolling larger sample sizes during a longer follow-up period can benefit the relevance of MSC transplantation in the restoration of spermatogenesis and treatment of male infertility. It seems that developing and utilizing stem cell transplantations, exosomes, scaffold delivery systems, and three dimensional (3D) culture methods may open a new window to getting more benefits from cell therapy in the treatment of men infertility.

The effect of topical magnesium on healing of pre-clinical burn wounds.

BACKGROUND: Magnesium (Mg) is an essential factor in the healing process. This study aimed to evaluate the effect of Mg creams on healing burn wounds in the rat model. METHODS: To induce burns under general anaesthesia, a 2 × 2 cm2, 100 °C plate was placed for 12 s between the scapulas in 100 male adult Sprague Dawley rats. Animals were divided into five groups (n = 20); positive control (induced burn without treatment); vehicle control (received daily Eucerin cream base topically); comparative control (induced burn and treated daily with Alpha burn cream topically); Treatment 1 and 2 (received daily Mg cream 2% and 4% topically, respectively). All animals were bled for hematological assessment of malondialdehyde (MDA) and TNF-α and sacrificed on days 0, 1, 7, 14, and 21 after interventions for biomechanical, histological, and stereological studies. RESULTS: Stereologically speaking, in treatment groups an increase in dermal collagen volume and fibroblasts was noticed. In treatment groups, the length of vessels, angiogenesis, and skin stretch increased, but the wound area, MDA, and TNF-α level decreased. CONCLUSION: Mg cream was effective in healing burns.

Characterization of Central and Nasal Orbital Adipose Stem Cells and their Neural Differentiation Footprints.

BACKGROUND: The unique potential of stem cells to restore vision and regenerate damaged ocular cells has led to the increased attraction of researchers and ophthalmologists to ocular regenerative medicine in recent decades. In addition, advantages such as easy access to ocular tissues, non-invasive follow-up, and ocular immunologic privilege have enhanced the desire to develop ocular regenerative medicine. OBJECTIVE: This study aimed to characterize central and nasal orbital adipose stem cells (OASCs) and their neural differentiation potential. METHODS: The central and nasal orbital adipose tissues extracted during an upper blepharoplasty surgery were explant-cultured in Dulbecco's Modified Eagle Medium (DMEM)/F12 supplemented with 10% fetal bovine serum (FBS). Cells from passage 3 were characterized morphologically by osteogenic and adipogenic differentiation potential and by flow cytometry for expression of mesenchymal (CD73, CD90, and CD105) and hematopoietic (CD34 and CD45) markers. The potential of OASCs for the expression of NGF, PI3K, and MAPK and to induce neurogenesis was assessed by real-time PCR. RESULTS: OASCs were spindle-shaped and positive for adipogenic and osteogenic induction. They were also positive for mesenchymal and negative for hematopoietic markers. They were positive for NGF expression in the absence of any significant alteration in the expression of PI3K and MAPK genes. Nasal OASCs had higher expression of CD90, higher potential for adipogenesis, a higher level of NGF expression under serum-free supplementation, and more potential for neuron-like morphology. CONCLUSION: We suggested the explant method of culture as an easy and suitable method for the expansion of OASCs. Our findings denote mesenchymal properties of both central and nasal OASCs, while mesenchymal and neural characteristics were expressed stronger in nasal OASCs when compared to central ones. These findings can be added to the literature when cell transplantation is targeted in the treatment of neuro-retinal degenerative disorders.

Cell Proliferation, Viability, Differentiation, and Apoptosis of Iron Oxide Labeled Stem Cells Transfected with Lipofectamine Assessed by MRI.

To assess in vitro and in vivo tracking of iron oxide labeled stem cells transfected by lipofectamine using magnetic resonance imaging (MRI), rat dental pulp stem cells (DPSCs) were characterized, labeled with iron oxide nanoparticles, and then transfected with lipofectamine to facilitate the internalization of these nanoparticles. Cell proliferation, viability, differentiation, and apoptosis were investigated. Prussian blue staining and MRI were used to trace transfected labeled cells. DPSCs were a morphologically spindle shape, adherent to culture plates, and positive for adipogenic and osteogenic inductions. They expressed CD73 and CD90 markers and lacked CD34 and CD45. Iron oxide labeling and transfection with lipofectamine in DPSCs had no toxic impact on viability, proliferation, and differentiation, and did not induce any apoptosis. In vitro and in vivo internalization of iron oxide nanoparticles within DPSCs were confirmed by Prussian blue staining and MRI tracking. Prussian blue staining and MRI tracking in the absence of any toxic effects on cell viability, proliferation, differentiation, and apoptosis were safe and accurate to track DPSCs labeled with iron oxide and transfected with lipofectamine. MRI can be a useful imaging modality when treatment outcome is targeted.

The predictive association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas: 4 decades follow up of 719 victims.

BACKGROUND: Respiratory diseases are the leading cause of morbidity and mortality in the survivors exposed to Sulfur Mustard (SM). The late abnormalities can be present as chronic bronchitis, tracheobronchial stenosis, asthma, bronchiectasis, airway narrowing, lung fibrosis, and lung cancers. This study aims to investigate the association between radiological findings and lung cancer development in patients exposed to sulfur mustard gas. METHODS: We entered 719 victims exposed to SM during the Iran-Iraq war into our follow-up study in a consensus manner. They were periodically followed with Chest HRCT scans from 2001 to an interval of 2014-2019. The mean year interval between exposure and the last follow-up was 38 years. For confirming the lung cancer in those with evidence of malignancy in their imaging, fine needle aspiration/biopsy and/or surgical intervention were done. RESULTS: Among 719 patients, 57% were free from any pathologic findings in their HRCT scan. Among the subjects who had the abnormal radiologic findings, Air Trapping (AT), Lung Fibrosis (LF), Bronchiectasis (B), and the evidence of lung cancer were found in 265 (36.9%), 207 (28.8%), 151 (21.0%), and 42 (5.8%), respectively. Adenocarcinoma (38.1%) was the most common type of cancer. The right lung was involved more than the left one regarding LF, B, and cancer (p value < 0.05). Considering the laterality, a significant correlation was found between the side of LF and B and the tumor side. Furthermore, it was shown that the lung lobes with LF were statistically correlated to tumor-involved lobes. The relative risk of AT and B existence for tumor development was 11.73 [4.87-28.26] and 10.14 [5.12-20.090], respectively. The most predictive finding was LF which caused the risk of developing tumor 17.75 [7.35-42.86] times higher in the patient with this pathology. By each increment of the number of LF and B, the risk of developing tumors increased by 51% and 76%, respectively. CONCLUSION: In survivors exposed to Sulfur Mustard, those with bronchiectasis and lung fibrosis have a significantly higher risk of developing lung cancers, so a close follow-up of these victims is recommended. Trial registration This study was confirmed by the institutional review board and ethics committee at Shiraz University of Medical Sciences (SUMS) with the ethical code IR.SUMS.MED.REC.1399.637.

MRI tracking of human Wharton's jelly stem cells seeded onto acellular dermal matrix labeled with superparamagnetic iron oxide nanoparticles in burn wounds.

Background: In vivo cell tracking after transplantation in regenerative medicine remains an unmet challenge and limits current understanding of the wound healing mechanism through cell-based therapies. This study investigated tracking of human Wharton's jelly stem cells (hWJSCs) seeded onto an acellular dermal matrix (ADM) and labeled with superparamagnetic iron oxide nanoparticles (SPIONs) by magnetic resonance imaging (MRI) in burn injury. Method: The hWJSCs were characterized and assessed for growth kinetics. A total of 30 rats were enrolled in three equal groups. Group 1 underwent scald burn injury left without treatment, the group 2 was treated by an ADM that was prepared from cosmetic surgery skin samples and the group 3 received hWJSCs labeled with SPIONs seeded onto an ADM. Tensile strength was evaluated before and after interventions, real time PCR assessed apoptosis, and Prussian blue staining, scanning electron microscopy (SEM) and MRI were used for the tracking of labeled cells. Results: The hWJSCs exhibited mesenchymal stem cell properties. Population doubling time was 40.1 hours. SPIONs did not show any toxic effect. The hWJSCs seeded onto an ADM decreased Bax and increased Bcl-2 gene expression. Internalization of SPIONs within hWJSCs was confirmed by Prussian blue staining, SEM and MRI until day 21. There was a significant difference between the Young's moduli of normal skin and the group receiving hWJSCs seeded onto an ADM. Histological observations and SEM imaging confirmed that MRI is an accurate method to track SPION-labeled hWJSCs in vivo. Conclusions: This study showed that SPION labeling coupled with MRI can be used to further understand the fate of stem cells after transplantation in a burn model.

in Vitro Effect of Methamphetamine on Proliferation, Differentiation and Apoptosis of Adipose Tissue Stem Cells.

PURPOSE: Among abused substances, methamphetamine is a psychostimulant drug widely used recreationally with public health importance. This study investigated the effect of methamphetamine on proliferation, differentiation, and apoptosis of human adipose tissue stem cells (AdSCs). METHODS: AdSCs were isolated from human abdominal adipose tissue and were characterized for mesenchymal properties and growth kinetics. MTT assay was undertaken to assess methamphetamine toxicity on proliferation and differentiation properties and apoptosis of hAdSCs. RESULTS: Isolated cells were shown to have mesenchymal properties and a population doubling time (PDT) of 40.1 h. Following methamphetamine treatment, expressions of KI-67 and TPX2 as proliferation genes and Col1A1 and PPARg as differentiation genes decreased. Methamphetamine administration increased the expression of Bax and decreased Bcl-2 genes responsible for apoptosis. CONCLUSIONS: Our data suggested when AdSCs were exposed to methamphetamine, it decreased proliferation and differentiation properties of stem cells together with an increase in apoptosis. These findings can be added to the literature, especially when methamphetamine is used recreationally for weight loss purposes.

Head and Neck Restoration in Scar Alopecia: Hair Transplantation in Scalp, Eyebrows, Beard and Mustache.

BACKGROUND: Surgical management of hair loss has become an increasingly challenging procedure, when dealing with scar alopecia. We investigated the efficacy of hair transplantation in patients with head and neck scar alopecia. METHODS: From 2016 to 2018 in Shiraz, Iran, all patients with scar alopecia in head and neck were evaluated for efficacy of follicular unit extraction (FUE), follicular unit transplantation (FUT) or a combination of two methods from donor sites in scalp and beard various hair-grafts were compared. RESULTS: Fifty-six patients were enrolled. Most of them were between 31 and 40 yr old (48.3%) and male (71.4%). Trauma, burn, surgical excision of adjacent skin, radiotherapy and leishmaniasis were the registered causes. Scars were visible in scalp (39.3%), beard (28.6%), eyebrow (21.4%), and moustache (10.7%) regions. FUE (87.5%), FUT (10.7%) and a combination (1.8%) were the used methods. One-hair-grafts were used in eyebrows (100%), moustache (100%), beard (88%) and scalp (7.9%), while 2-hair-grafts in beard (6%) and scalp (47.4%) and 3-haired grafts in beard (6%) and scalp (44.7%) transplantations. CONCLUSION: In head and neck scar alopecia, hair transplantation was selected based on type and depth of scar. FUE was targeted when huge grafts were not needed, including beard, moustache, and eyebrow, while FIT was used when extensive scars were present in scalp. One-hair-grafts were mostly applied for eyebrow, moustache and beard, 2-hair- and 3-hair- grafts for beard and scalp transplantation. These findings can be added to the literature when FUE, FIT, or their combination are targeted in hair restoration of scar alopecia in head and neck.

Achievements and Challenges in Transplantation of Mesenchymal Stem Cells in Otorhinolaryngology.

Otorhinolaryngology enrolls head and neck surgery in various tissues such as ear, nose, and throat (ENT) that govern different activities such as hearing, breathing, smelling, production of vocal sounds, the balance, deglutition, facial animation, air filtration and humidification, and articulation during speech, while absence of these functions can lead to high morbidity and even mortality. Conventional therapies for head and neck damaged tissues include grafts, transplants, and artificial materials, but grafts have limited availability and cause morbidity in the donor site. To improve these limitations, regenerative medicine, as a novel and rapidly growing field, has opened a new therapeutic window in otorhinolaryngology by using cell transplantation to target the healing and replacement of injured tissues. There is a high risk of rejection and tumor formation for transplantation of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs); mesenchymal stem cells (MSCs) lack these drawbacks. They have easy expansion and antiapoptotic properties with a wide range of healing and aesthetic functions that make them a novel candidate in otorhinolaryngology for craniofacial defects and diseases and hold immense promise for bone tissue healing; even the tissue sources and types of MSCs, the method of cell introduction and their preparation quality can influence the final outcome in the injured tissue. In this review, we demonstrated the anti-inflammatory and immunomodulatory properties of MSCs, from different sources, to be safely used for cell-based therapies in otorhinolaryngology, while their achievements and challenges have been described too.

Spinal cord injury repair using mesenchymal stem cells derived from bone marrow in mice: A stereological study.

Transplantation of bone marrow stem cells (BMSCs) has shown to have a vital role in promoting nerve regeneration after SCI. The aim of this study was to investigate the effect of BMSCs transplantation in healing of spinal cord injury (SCI) in mice based on morphologic parameters. Forty two male mice were randomly divided into 3 groups of control with no intervention, experimental SCI without treatment, and experimental SCI transplanted with 2 × 105 BMSCs intravenously. To induce SCI bilaterally, T10 was compressed for 2 min. The animals were sacrificed 3 and 5 weeks after SCI and T7-T11 segments of spinal cord were removed and stained by Giemsa and H&E methods. Stereological assessment estimated the gray and white matter volume, the number of neurons and neuroglia and diameter of central canal. The average amount of gray matter in SCI injury group was significantly lower than control group. An increase in the number of neurons was noted after cell transplantation. The number of neurons in SCI injury group significantly decreased in comparison to the control group. In cell transplantation group, a significant increase in the number of neurons was visible when compared to SCI injury group. The increase in the number of neurons after cell transplantation denotes to the regenerative potential of BMSCs in SCI. These findings can be added to the literature and open a new window when targeting treatment of SCI.

Histological Changes in Adipose Tissue: An Alarm When Methamphetamine Is Targeted for Weight Loss Purposes.

BACKGROUND: Methamphetamine (METH) may be administered for weight loss purposes and to understand the METH side-effects more in details, this study aimed at determining the effect of METH on changes in adipose tissue in experimental rats. METHODS: Forty five male Wistar rats were randomly allocated to three equal groups. Group 1 was experimental receiving METH [0.4 mg/kg, subcutaneously (S/C), 0.6 mL/rat] for 3 weeks, group 2 was the sham group receiving normal saline (0.6 mL/rat, S/C) and the 3rd group was the control receiving distilled water, identically. The elevated plus maze test was used to confirm cognitive impairment and distraction as anxiety and to verify addiction to METH by assessing the percent time spent in open arm (OAT), the percent time spent in closed arm (CAT), the percent time spent in central parts and head dipping over the side of the maze. Adipose tissue was assessed histologically 7, 14 and 21-days after interventions. RESULTS: A significant increase in anxiety level, and histologically inflammation, degeneration and necrosis in adipose tissue were visible after METH use. CONCLUSION: METH use resulted in a significant inflammation and necrosis in adipose tissue denoting to the dangers of METH use, when recreationally targeted for weight loss purposes.

The Epidemiology of Burn and Lethal Area of Fifty Percentage (LA50) in Children in Shiraz, Southern Iran.

BACKGROUND: This study was conducted to assess the epidemiology of burn and lethal area of fifty percentage (LA50) in children in Shiraz, Southern Iran. METHODS: In this case series study, 619 hospitalized burn children from burn centers affiliated to Shiraz University of Medical Sciences, Shiraz, Iran from 2012 to 2016 were enrolled. Demographic characteristics of patients such as age, gender, place and cause of burn, and morality rate were evaluated. LA50 was measured using Probit analysis. RESULTS: The mean age of patients was 4.4±3.4 years. The mortality rate in burn patients was 8.7% and LA50 of total body surface area (TBSA%) ranged from 40.1% in 2012 to 68.3% in 2016. Although the number of male burn patients (65%) was more than females (35%), the mortality rate in females was more than males (11.4% vs. 7.2%). Scald and flame were the most common causes of burn. CONCLUSION: The findings in our burn center comparing burn patients to developed countries showed that LA50 and survival rate were lower denoting to an urgent necessity to promote current policies in burn care and prevention and to decrease the mortality rate too.

The effect of yogurt fortified with Lactobacillus acidophilus and Bifidobacterium sp. probiotic in patients with lactose intolerance.

This study assessed the effect of probiotic yogurt fortified with Lactobacillus acidophilus and Bifidobacterium sp. in patients with lactose intolerance. Fifty-five patients suffering from lactose intolerance were randomly divided into control group of 28 lactose intolerance patients who received nonprobiotic yogurt (100 ml) and experimental group consisted of 27 lactose intolerance patients who received probiotic yogurt fortified (100 ml) with L. acidophilus and Bifidobacterium sp. Each individual received yogurt for one week. Lactose intolerance was confirmed when the patients received 75 g lactose and were positive after 30 min until 3 hr for lactose intolerance symptoms and by hydrogen breath test (HBT). After intervention, the hydrogen level was lower in experimental group in comparison with the control group. Lactose intolerance symptoms in experimental group were much less than the control group. Our findings revealed that probiotic yogurt fortified with L. acidophilus and Bifidobacterium sp. could safely and effectively decrease lactose intolerance symptoms and HBT, so our probiotic can be recommended as a treatment of choice in lactose intolerance patients.

Proliferative and Regenerative Effect of Acetonic Extract of Feijoa sellowiana on Stem Cells.

BACKGROUND: Feijoa is widely used in medicine due to their anti-inflammatory, antioxidant, antimicrobial and antitumor properties. The current investigation studied the proliferative and regenerative effect of acetonic extract of Feijoa sellowiana on stem cells. METHODS: Acetone extract of Feijoa was prepared using percolator and rotary machines. Human bone marrow stem cells (hBMSCs) were used as experimental in vitro model and characterized morphologically, by flowcytometry, and differentiation properties. The toxicity of the extract on hBMSCs was determined by MTT assay. The viability and growth kinetics of hBMSCs treated to Feijoa was determined. Real time PCR was used for changes in expression of proliferative and apoptotic genes on day 7th. RESULTS: MTT assay demondtrated that Feijoa at doses less than 200 ng/ml did not show any cytotoxic effect on hBMSCs and increased the cell proliferation until day 3rd followed by a non-significant slow decreasing trend until day 7th. Population doubling time (PDT) showed a decline until day 3rd followed by an increase until day 7th. A significant rise in expression of Bax and decline in Bcl-2 expression were noted on day 7th. CONCLUSION: The modulatory activity of Feijoa may be responsible for its increasing effect on cell proliferation till day 3rd. Therefore, when faster proliferation during a shorter time period is targeted, Feijoa can be safely added to the culture media in the first three days.

Therapeutic Effect of Mesenchymal Stem Cells in Ulcerative Colitis: A Review on Achievements and Challenges.

The worldwide epidemiology of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), still shows an increasing trend in Asia and Iran. Despite an improvement in the treatment landscape focused on symptomatic control, long-term colectomies have not decreased over the last 10-year period. Thus, novel therapies are urgently needed in clinics to supplement the existing treatments. Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunosuppressive effects, targeting IBD as a new treatment strategy. They have recently received global attention for their use in cell transplantation due to their easy expansion and wide range of activities to be engrafted, and because they are home to the mucosa of the intestine. Moreover, MSCs are able to differentiate into epithelial and other cells that can directly promote repair in the mucosal damages in UC. It seems that there is a need to deepen our understanding to target MSCs as a promising treatment option for UC patients who are refractory to conventional therapies. Here, we overviewed the therapeutic effects of MSCs in UC and discussed the achievements and challenges in the cell transplantation of UC.

The effect of allogenic human Wharton's jelly stem cells seeded onto acellular dermal matrix in healing of rat burn wounds.

BACKGROUND: Various methods were introduced to overcome the autograft shortage in burn wound care, including cell transplantation and tissue engineering. AIMS: To evaluate the healing effect of allogenic human Wharton's jelly stem cells (hWJSCs) seeded onto acellular dermal matrix (ADM) in rat burn injuries. PATIENTS AND METHODS: Human Wharton's jelly stem cells provided from umbilical cord tissue were characterized before transplantation, and the growth kinetic was determined. Skin samples from cosmetic surgeries were used for preparation of ADM. Forty male Sprague Dawley rats were randomly divided into 4 equal groups. Third-degree burn was induced for all animals by exposing to hot water using a 2 cm ring for 10 seconds. Group 1 was burned rats that did not receive any treatment. After burn injury, the second group received silver sulfadiazine (SSD), the third group was treated just by using ADM, and the fourth group received 2 × 106 hWJSCs seeded onto ADM. The animals were euthanized for histologic evaluation after 7, 14, and 21 days. RESULTS: Human Wharton's jelly stem cells were characterized to be spindle shape and positive for osteogenic and adipogenic induction and for mesenchymal markers but lacked hematopoietic markers. Population doubling time (PDT) was 40.1 hours with an increasing growth trend until day 6th. Macro- and microscopically, the healing was mild in ADM group and moderate in ADM + hWJSCs group after 21 days. CONCLUSION: Allogenic hWJSCs seeded onto ADM improved the healing process in burn wounds denoting to their therapeutic and anti-inflammatory effects in burn wounds that can be added to the literature.

Mortality and Body Mass Index in Burn Patients: Experience from a Tertiary Referral Burn Center in Southern Iran.

BACKGROUND: The role of obesity has been widely studied as a determinant factor of increasing mortality in surgical patients. In this study we aimed to investigate the association of mortality determinants with obesity classification and BMI score in burn patients admitted to a tertiary referral center in Southern Iran. METHODS: In this retrospective cross-sectional study, medical profiles of burn patients admitted from 2016 to 2017 were obtained from Amiralmomenin Burn Hospital, a tertiary referral burn center affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Demographic, and clinical characteristics as well as patient outcomes were recorded to determine prognostic factors in fatal burns based on anthropometric measurements. RESULTS: Among 101 patients who were enrolled in this study including 73 males and 28 females, mean age was 34.85±12.04 years, total burn surface area (TBSA) was 37.37 (10.50%), BMI was 25.46±5.33 kg/m2 and hospital stay was 22.28±13.62 days. Overall mortality rate was 24.7% with 25 expired cases. Logistic regression demonstrated significant association of older age, male gender, and greater TBSA with mortality. However, difference in mortality rate in patients with BMI of 25 kg/m2 (27.4%) in comparison to patients with BMI<25 kg/m2 (18%) did not reach statistical significance. CONCLUSION: Although patients with higher BMI had increased mortality rate following burn injury, this finding showed no significant association. Further studies with larger samples may be necessary to conclude a causal association between BMI and mortality in burn patients.

Evaluation of VEGF, FGF and PDGF and Serum Levels of Inflammatory Cytokines in Patients with Glioma and Meningioma in Southern Iran.

BACKGROUND: Meningioma and glioma are common central nervous system tumors. Hypoxic tumor cells secrete angiogenic cytokines, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) that stimulate neovascular formation and inflammatory cytokine, such as TNF-α and IL-1ß. We measured these serum levels in patients with glial cell tumors and meningioma. MATERIALS AND METHODS: This was a case-control study in 2014-2015 on patients diagnosed with meningioma/glioma. All demographic and clinical data were registered. The tumor volume and intraoperative bleeding were recorded. Serum levels of VEGF, PDGF, FGF, TNF-α and IL-1ß were measured by ELISA methods. RESULTS: Ninety-six patients were enrolled in this study, 32 in each group. Patients VEGF level with cranial tumor, glioma/meningioma had increased. VEGF level was highest among grade IV tumors, larger tumors, and in glioblastoma multiform. There was an upsurge in VEGF serum level as glioma grade increased. The highest VEGF levels were seen in parasagittal meningioma. In contrast to VEGF, PDGF was slightly elevated in glial cell tumors, which was significantly elevated in meningioma. Higher PDGF correlated with increased intraoperative bleeding, especially in meningioma cases. Oligodendroglial tumors expressed higher PDGF levels in contrast to other glial tumors. FGF level was not statistically significant. TNF-α and IL-1ß expressions were significantly higher in the meningioma and glioma group in comparison to control group. CONCLUSION: We found increased VEGF and PDGF serum levels in CNS patient's tumor. A different role for PDGF was found in the pathogenesis of neovascularization of meningioma, as well as oligodendroglioma. No significant result was found for FGF. TNF-α and IL-1ß can serve as key prognostic biomarker in high-grade glioma and meningioma patients.

MRI-Tracking of Dental Pulp Stem Cells In Vitro and In Vivo Using Dextran-Coated Superparamagnetic Iron Oxide Nanoparticles.

The aim of this study was to track dental pulp stem cells (DPSCs) labeled with dextran-coated superparamagnetic iron oxide nanoparticles (SPIONs) using magnetic resonance imaging (MRI). Dental pulp was isolated from male Sprague Dawley rats and cultured in Dulbecco's modified Eagle's medium F12 (DMEM-F12) and 10% fetal bovine serum. Effects of SPIONs on morphology, viability, apoptosis, stemness, and osteogenic and adipogenic differentiation of DPSCs were assessed. Prussian blue staining and MRI were conducted to determine in vitro efficiency of SPIONs uptake by the cells. Both non-labeled and labeled DPSCs were adherent to culture plates and showed spindle-shape morphologies, respectively. They were positive for osteogenic and adipogenic induction and expression of cluster of differentiation (CD) 73 and CD90 biomarkers, but negative for expression of CD34 and CD45 biomarkers. The SPIONs were non-toxic and did not induce apoptosis in doses less than 25 mg/mL. Internalization of the SPIONs within the DPSCs was confirmed by Prussian blue staining and MRI. Our findings revealed that the MRI-based method could successfully monitor DPSCs labeled with dextran-coated SPIONs without any significant effect on osteogenic and adipogenic differentiation, viability, and stemness of DPSCs. We provided the in vitro evidence supporting the feasibility of an MRI-based method to monitor DPSCs labeled with SPIONs without any significant reduction in viability, proliferation, and differentiation properties of labeled cells, showing that internalization of SPIONs within DPSCs were not toxic at doses less than 25 mg/mL. In general, the SPION labeling does not seem to impair cell survival or differentiation. SPIONs are biocompatible, easily available, and cost effective, opening a new avenue in stem cell labeling in regenerative medicine.

The healing effect of Wharton's jelly stem cells seeded on biological scaffold in chronic skin ulcers: A randomized clinical trial.

BACKGROUND: Chronic wound or nonhealing ulcer is essentially a wound that does not progress normally through the wound healing process. This study assessed the healing effect of umbilical cord Wharton's jelly stem cells seeded on biological scaffold in chronic skin ulcers. MATERIALS AND METHODS: In a randomized clinical trial, five patients between 30 and 60 years with chronic diabetic wounds were enrolled. To cover the wounds, acellular amniotic membrane seeded with Wharton's jelly mesenchymal stem cells (WJSCs) was used for 9 days, every 3 days with a follow-up of 1 month. The percentage and time of wound healing and the size of wound were recorded for each patient. RESULTS: In treated patients, the wound healing time and wound size significantly decreased, and after 6 and 9 days, the wound size significantly declined (P < 0.002). CONCLUSION: As WJSCs seeded on amniotic membrane could significantly accelerate the healing effect in chronic diabetic wounds, they can be an alternative source in tissue engineering and repair of chronic ulcers.