Stem Cell Group Research Articles

The effect of preconditioning hypoxia in schwann-like-cells-derived adipose mesenchymal stem cells and rat sciatic nerve-derived stem cells: experimental research.

This study aims to explore the response of Schwann-like cells derived from adipose-derived mesenchymal stem cells (SLCs) and Schwann cells rat sciatic nerve-derived stem cells (SCs) with their secretomes under normoxic and hypoxic conditions in vitro. SLCs and SCs were isolated from the adipose tissue and the sciatic nerve of the adult white male rat strain Wistar. Cells were incubated in 21% O2 (normoxic group) and 1%, 3%, and 5% O2 (hypoxic group) conditions. Concentration values of transforming growth factor-β (TGF-β), basic Fibroblast Growth factor (bFGF), brain-derived neurotrophic factor, glial-derived neurotrophic factor, vascular endothelial growth factor, and nerve growth factor were detected and calculated utilizing an enzyme-linked immunosorbent assay, and the growth curve was described. SLCs and SCs indicated positive expression for mesenchymal markers and negative expression for hematopoietic markers. Normoxic conditions SLCs and SCs showed elongated and flattened morphology. Under hypoxic conditions, SLCs and SCs showed a classic fibroblast-like morphology. Hypoxia 1% gave the highest concentration in TGF-β and bFGF from the SLCs group and TGF-β, bFGF, brain-derived neurotrophic factor, and vascular endothelial growth factor from the SCs group. No significant differences in concentration of growth factors between the SLCs group compared to SCs group in all oxygen groups. Preconditioning hypoxia has an effect on the composing of SLCs, SCs, and their secretomes in vitro; no significant differences in concentration of growth factors between the SLCs group compared with the SCs group in all oxygen groups.

Hair follicle stem cell proliferation and differentiation are achieved by miR-1285-3P through targeted regulation of NOTCH pathway

The purpose of this experiment is to understand how miR-1285-3P regulates the NOTCH signaling pathway by targeting, thereby affecting the proliferation and differentiation of hair follicle stem cells. The cultured Inner Mongolia hair follicle stem cells were used in this experiment, and they were divided into control group, blank transfection group and miR-1285-3P transfection group. Among them, the control group was left untreated; the blank group was given miR-NC transfection; at the same time, the miR-1285-3P transfection group was given miR-1285-3P mimics for transfection. Compared with the control group (97.24 ± 6.81) and blank gro transfection up (97.32 ± 7.20), the cell proliferation ability of the miR-1285-3P transfection group (49.31 ± 3.39) was significantly lower. Compared with the other two groups, The proliferation ability of cells in the miR-1285-3P transfection group was decreased (P < 0.05); compared with the S-phase hair follicle stem cells in the control group (19.23 ± 1.29) and blank transfection group (19.38 ± 1.45), the miR-1285-3P transfection group (15.26 ± 1.26) decreased more significantly (P < 0.05). For hair follicle stem cells in each group, the proportion of cells in the G0-G1 phase was significantly different between the blank transfection group (63.18 ± 2.78) and the control group (64.29 ± 2.09), and the blank transfection group had a higher proportion (P < 0.05). In the process of miR-1285-3P targeting and regulating NOTCH signaling pathway, the proliferation and differentiation ability of hair follicle stem cells is affected. When NOTCH signaling pathway is activated, the differentiation of hair follicle stem cells is accelerated.

Pulp-Dentin Complex Regeneration with Cell Transplantation Technique Using Stem Cells Derived from Human Deciduous Teeth: Histological and Immunohistochemical Study in Immunosuppressed Rats.

The aim of this study was to histologically verify the performance of pulp-derived stem cells used in the pulp-dentin complex regeneration. Maxillary molars of 12 immunosuppressed rats were divided into two groups: the SC (stem cells) group, and the PBS (just standard phosphate-buffered saline) group. After pulpectomy and canal preparation, the teeth received the designated materials, and the cavities were sealed. After 12 weeks, the animals were euthanized, and the specimens underwent histological processing and qualitative evaluation of intracanal connective tissue, odontoblast-like cells, intracanal mineralized tissue, and periapical inflammatory infiltrate. Immunohistochemical evaluation was performed to detect dentin matrix protein 1 (DMP1). In the PBS group, an amorphous substance and remnants of mineralized tissue were observed throughout the canal, and abundant inflammatory cells were observed in the periapical region. In the SC group, an amorphous substance and remnants of mineralized tissue were observed throughout the canal; odontoblasts-like cells immunopositive for DMP1 and mineral plug were observed in the apical region of the canal; and a mild inflammatory infiltrate, intense vascularization, and neoformation of organized connective tissue were observed in the periapical region. In conclusion, the transplantation of human pulp stem cells promoted partial pulp tissue neoformation in adult rat molars.

ЭФФЕКТИВНОСТЬ ИСПОЛЬЗОВАНИЯ СТВОЛОВЫХ КЛЕТОК В ЛЕЧЕНИИ ЦИРРОЗА ПЕЧЕНИ (ЭКСПЕРИМЕНТАЛЬНОЕ ИССЛЕДОВАНИЕ)

Rationale. The need to find the most effective ways to restore liver function in cirrhosis. Goal. To evaluate the effectiveness of using cellular technologies in liver cirrhosis in an experiment.Materials and methods. The experiment included 132 individuals of c57black mice aged 12 to 18 weeks. All individuals are divided into 5 groups (30 individuals in group’s №1– №3, №5 and 12 individuals in group №4). Individuals of group 5 were removed from the experiment before it began in order to determine the normal weight of the liver and spleen. A model of liver cirrhosis was created for individuals of groups 1– 4. Group 4 individuals were removed from the experiment 30 days after the model was formed to confirm the presence of liver cirrhosis. Individuals of group 1 were given intravenous stem cells. Individuals of group 2 were intraportally injected with stem cells. Individuals of group 3 were not injected with stem cells. Changes in all three groups were evaluated 30 days after cell therapy.Results. Against the background of cell therapy, the greatest decrease in liver mass is observed in group 2 (intraportal administration of stem cells), where the liver mass exceeds normal values by 7%. In second place is group 1 (intravenous administration of stem cells), where the liver mass is higher than normal by 17%. In group 3, the liver mass exceeds normal values by 25.3%. The spleen mass 30 days after the application of cell technologies in the second group differed from normal values by 0.01 g; in group 1-by 0.06 g; in group 3-by 0.1 g. The level of total protein 30 days after the introduction of stem cells in group 1 increased by 5.9%; in group 2 by 28.8%; in group 3 by 1.1%. Albumin levels increased by 11% in group 1, 33.8% in group 2, and remained unchanged in group 3. The ALT level in group 1 decreased by 32.3%, in group 2 by 48.1%, and in group 3 remained unchanged. The AST level decreased by 7% in group 1, by 25.9% in group 2, and remained unchanged in group 3. Indicators of alkaline phosphatase decreased by 3.9% in group 1, by 14.3% in group 2, and did not improve in group 3.Conclusion. The use of cellular technologies in liver cirrhosis contributes to a faster recovery of liver function when intraportal introduction of cellular structures.

P-795 Comparison of intra-ovarian platelet rich plasma versus autologous bone marrow derived stem cell instillation in women with diminished ovarian reserve for ovarian rejuvenation

Study questionTo compare role of intra-ovarian platelet rich plasma (PRP) versus marrow derived stem cell (SC) instillation for improvement in ovarian reserve (AFC, AMH and FSH)Summary answerBoth PRP and SC therapy improves the ovarian reserve however, response to PRP is superior to SC post interventionWhat is known alreadyWith increasing incidence of females with diminished ovarian reserve (DOR), posing a serious challenge in terms of limited treatment options for these couples. Clinicians are trying to find effective strategies besides oocyte donation or adoption Of late, novel ovarian rejuvenation approaches has been investigated which are currently available for research purposes only. Multiple studies are evaluating effect of intra-ovarian PRP or autologous SC instillation, the results are encouraging as they are showing improvement in ovarian reserve thus bringing a paradigm shift in treatment options. None of the published studies so far have compared PRP versus SC in DOR population.Study design, size, durationA prospective comparative study was conducted at Division of Reproductive Medicine of a tertiary care institute. 72 infertile females (20-39 years) with poor ovarian reserve (AMH <1.2 ng /ml; AFC<5) were enrolled in the study between January 2020 to December 2021. The two comparative groups underwent either intra-ovarian PRP instillation (n = 42) or autologous SC transplantation (n = 30).Participants/materials, setting, methodsAfter the two groups were matched (PRP vs SC) for baseline characteristics (Age, AMH, AFC, FSH, Estradiol), 30 subjects in each group were compared for change in serum FSH/AMH/Estradiol levels, AFC, right and left ovarian volume at 1st month and 3rd month post intervention from the baseline. This was also compared between the two groups using Student t-test. The cost and procedural pain measured using Visual analog scale (VAS) were also compared between the groups.Main results and the role of chanceAfter matching for baseline characteristics, significant ∼ 1.8/2 and ∼1.5/1.6 fold increase in AFC at 1st/3rd month post intervention (p<0.001) was observed after PRP instillation and SC transplantation respectively. This significant improvement was observed more in PRP group than SC group at 3rd month post intervention (7.07 vs 5.60, p=0.02), while no significant difference existed at 1st month of follow up. However, there was no significant improvement in serum FSH, AMH and Estradiol levels (p0.05) from the baseline at 1st and 3rd month post intervention in both the groups. Similarly, there was no significant difference between the two groups in serum FSH level (7.98 IU/ml vs 9.62 IU/ml, p=0.062; 8.26 IU/ml vs 9.50 IU/ml, p=0.15), AMH level (1.62 ng/ml vs 1.02 ng/ml, p=0.27; 1.35 ng/ml vs 0.95 ng/ml, p=0.24), Estradiol level (49.12 pg/ml vs 56.48 pg/ml p=0.443; 54.7 pg/ml vs 61.12 pg/ml, p=0.44), right ovarian volume (3.13 cm3 vs 2.49 cm3, p=0.06; 3.37 cm3 vs 2.74 cm3,p=0.063) and left ovarian volume (2.98 cm3 vs 2.47 cm3, p=0.102; 2.87 cm3 vs 2.34 cm3,p=0.103) at 1st and 3rd month post intervention respectively. PRP was more cost-effective and associated with less pain (32.5 mm vs 28.13 mm, p=0.02), and better patient compliance.Limitations, reasons for cautionThis was a comparative study and the participants were not randomized but were matched for the baseline characteristics. Also due to impact of Covid-19 causing intermittent pause in nonessential facilities like IVF services, a smaller sample size could be enrolled and also clinical outcomes could not be evaluatedWider implications of the findingsThis study, although comparative, for the first time highlights the beneficial role of PRP over SC, thus can establish superiority of PRP as minimally invasive, economical, patient friendly and a recommended therapy for ovarian rejuvenation and folliculogenesis, providing the DOR females an opportunity to produce their own offspring.Trial registration numberCTRI/2020/01/022726

Role of stem cells-based in facial nerve reanimation: A meta-analysis of histological and neurophysiological outcomes.

BACKGROUNDTreatments involving stem cell (SC) usage represent novel and potentially interesting alternatives in facial nerve reanimation. Current literature includes the use of SC in animal model studies to promote graft survival by enhancing nerve fiber growth, spreading, myelinization, in addition to limiting fibrotic dege neration after surgery. However, the effectiveness of the clinical use of SC in facial nerve reanimation has not been clarified yet.AIMTo investigate the histological, neurophysiological, and functional outcomes in facial reanimation using SC, compared to autograft.METHODSOur study is a systematic review of the literature, consistently conducted according to the preferred reporting items for systematic reviews and meta-analyses statement guidelines. The review question was: In facial nerve reanimation on rats, has the use of stem cells revealed as effective when compared to autograft, in terms of histological, neurophysiological, and functional outcomes? Random-effect meta-analysis was conducted on histological and neurophysiological data from the included comparative studies.RESULTSAfter screening 148 manuscript, five papers were included in our study. 43 subjects were included in the SC group, while 40 in the autograft group. The meta-analysis showed no significative differences between the two groups in terms of myelin thickness [CI: -0.10 (-0.20, 0.00); I2 = 29%; P = 0.06], nerve fibers diameter [CI: 0.72 (-0.93, 3.36); I2 = 72%; P = 0.6], compound muscle action potential amplitude [CI: 1.59 (0.59, 3.77); I2 = 89%; P = 0.15] and latency [CI: 0.66 (-1.01, 2.32); I2 = 67%; P = 0.44]. The mean axonal diameter was higher in the autograft group [CI: 0.94 (0.60, 1.27); I2 = 0%; P ≤ 0.001].CONCLUSIONThe role of stem cells in facial reanimation is still relatively poorly studied, in animal models, and available results should not discourage their use in future studies on human subjects.

Effects of Coculture Fibroblasts and Vascular Endothelial Cells on Proliferation and Osteogenesis of Adipose Stem Cells.

Background The development of tissue engineering provides a new method for the clinical treatment of bone defects, but the problems of slow formation and slow vascularization of tissue engineered bone have always existed. Studies have shown that the combined culture system of vascular endothelial cells and adipose stem cells is superior to single cell in repairing bone defects. With the excellent proliferation ability, secretion of synthetic collagen and a variety of regulatory factors and fibroblasts can differentiate into osteoblasts and have the potential to be excellent seed cells involved in tissue engineering bone construction. Objective To investigate the effects of combined culture of fibroblasts, vascular endothelial cells, and adipose stem cells on proliferation and osteogenic differentiation of adipose stem cells. Methods The cells were divided into 4 groups: adipose stem cell group, adipose stem cell+vascular endothelial cell coculture group, adipose stem cell+fibroblast coculture group, and adipose stem cell+vascular endothelial cell+fibroblast coculture group. The morphological changes of the cells were observed under an inverted microscope. After 1, 3, 5, 7, and 9 days of coculture, the proliferation of adipose stem cells in each group was detected by a CCK-8 method and the growth curve was plotted. Adipose stem cells in each group were stained with alizarin red and alkaline phosphatase at days 7, 14, 21, and 28. At the third week of coculture, Western blot was used to detect the expression level of bone morphogenetic protein 2 of adipose stem cells in each group. Results and Conclusions. (1) After 14 days of culture, some cells in the adipose stem cell+vascular endothelial cell+fibroblast coculture group fused into clumps and distributed in nests, while the adipose stem cells in the adipose stem cell group had a single cell morphology and no cell clusters were observed. (2) The cell growth curves were basically the same in each group, and the absorbance value increased gradually. The absorbance value of the adipocyte+vascular endothelial cell+fibroblast coculture group was the highest, followed by the adipocyte+fibroblast coculture group and then the adipocyte+fibroblast coculture group. (3) Alizarin red staining showed negative reaction in each group on the 7th day, and a small number of red positive cells gradually appeared in each group as time went on. On the 28th day, red positive cells were found in all groups, and most of them were in the coculture group of adipose stem cells+vascular endothelial cells+fibroblasts, showing red focal. The coculture group of adipose stem cells+vascular endothelial cells and adipose stem cells+fibroblasts was less, and the adipose stem cell group was the least. On day 28 of alkaline phosphatase staining, cells in each group had red positive particles, and the adipose stem cell+vascular endothelial cell+fibroblast coculture group and adipose stem cell+fibroblast coculture group had the most, followed by the adipose stem cell+vascular endothelial cell coculture group and then the adipose stem cell group. (4) Bone morphogenetic protein 2 was expressed in all groups, especially in adipose stem cell+fibroblast coculture group and adipose stem cell+vascular endothelial cell+ fibroblast coculture group. (5) Fibroblast could promote adipose stem cell osteogenic differentiation better than vascular endothelial cells, but the proliferation effect was not as good as vascular endothelial cells. The coculture system of fibroblast combined with vascular endothelial cells and adipose stem cells promoted the proliferation of adipose stem cells and the rapid and efficient differentiation of adipose stem cells into osteoblasts.

Application of Polymer Drugs with Cerium Dioxide Nanomolecules and Mesenchymal Stem Cells for the Treatment of Skin Wounds in Aged Rats.

The urgency of the problem of wound healing is not in doubt, given the global trend of an increase in the number of operations and injuries with skin damage, as well as the lack of universal means of treating wounds. Study Objective: To compare the effectiveness of the developed drugs, smart polymeric nano-drug with cerium oxide nanoparticles (SPN), and smart polymeric nano-drug in combination with mesenchymal stem cells (SPN + SC) on the healing process of skin wounds. Material and methods. An experimental study was carried out using Wistar rats of post-reproductive age, which had dermis and epidermis removed on their backs. There were four groups of wounds in total: control, treatment with mesenchymal stem cells (SC), SPN, and SPN + SC. Results. A positive therapeutic effect of polymeric drugs on the dynamics of wound area reduction was established, which was most typical for wounds of the SPN group and, particularly, the SPN + SC group. On the third day, an anti-inflammatory effect was revealed in the SC and the SPN + SC groups in particular, which was expressed in a reduced leukocyte infiltration and an increase in the level of microcirculation during this period. The fastest transition from the phase of exudation to proliferation was recorded in the SPN and SPN + SC groups. Histologically, these groups showed faster regeneration, including the epithelialization of wounds. Conclusion. The results obtained in the course of the study open up possibilities for the development of fundamentally new, highly effective wound healing agents.

Effect of mesenchymal bone marrow stem cells on the periodontal ligament of induced Diabetic Rats.

Introduction: Considering the Diabetes mellitus (DM) as one of the oldest condi­tions characterized in humans, it has been recognized since antiquity and considered as a major health problem at present. There is a need for efficient treatment. Aim: The aim of the present investigation was to find out whether stem cells can alleviate the well documented side effects of streptozotocin induced diabetes mellitus on the periodontal ligament of adult male albino rats. Material and Methods: Sixty adult male albino rats with body were used in this investigation. They were divided into the following three groups; Group 1: consisted of 20 animals and served as controls; Group 2: consisted of 20 animals, they were subjected to a single intraperitoneal injection of streptozotocin in a dose of 60mg. /kg body weight for induction of diabetes mellitus; Group 3: consisted of 20 animals. They were subjected to induction of diabetes mellitus in the same way as group 2 animals. One week later, the animals were subjected to a single intravenous infusion of mesenchymal bone marrow stem cells. At the end of the experiment one week later the animals were euthanized by cervical dislocation, their jaws dissected out, decalcified then processed for A. histological examination (Hematoxylin and Eosin stain) B. transmission electron microscope. Results: Histological examination in the present work showed that the treatment of diabetic rats with stem cells resulted in ame­lioration of the degenerative effects of diabetes on the periodontal ligament in group 2 and regenerative changes of stem cells in group 3 compared to the control group 1. Electron microscopic examination of the PDL showed marked regenerative changes in the density of collagen. Conclusion: Diabetic albino rats treated with stem cells revealed partial improvements, mostly in the arrangement of the fibers of periodontal ligament. The ultrastructural features showed normal fibroblasts.

Stem Cells and Platelet-Rich Plasma Enhance the Healing Process of Tendinitis in Mice.

Objective Achilles tendon pathologies occur frequently and have a significant socioeconomic impact. Currently, there is no evidence on the best treatment for these pathologies. Cell therapy has been studied in several animal models, and encouraging results have been observed with respect to tissue regeneration. This study is aimed at evaluating the functional and histological effects of bone marrow stem cell or platelet-rich plasma implantation compared to eccentric training in the treatment of Achilles tendinopathy in rats. Methods Fourty-one male Wistar rats received collagenase injections into their bilateral Achilles tendons (collagenase-induced tendinopathy model). The rats were randomly divided into four groups: stem cells (SC), platelet-rich plasma (PRP), stem cells+platelet-rich plasma (SC+PRP), and control (eccentric training (ET)). After 4 weeks, the Achilles tendons were excised and subjected to biomechanical and histological analyses (Sirius red and hematoxylin-eosin staining). Results Biomechanical assessments revealed no differences among the groups in ultimate tensile strength or yield strength of the tendons (p = 0.157), but there were significant differences in the elastic modulus (MPa; p = 0.044) and maximum tensile deformation (p = 0.005). The PRP group showed the greatest maximum deformation, and the SC group showed the highest Young's modulus (elasticity) measurement. In histological analysis (hematoxylin-eosin and Sirius red staining), there were no differences among the groups. Conclusion PRP and SC+PRP yielded better biomechanical results than eccentric training, showing that these treatments offer better tend function outcomes. This theoretical rationale for the belief that cell therapies can serve as viable alternatives to current treatments chronic fibrotic opens the door for opportunities to continue this research.

CD34+ Cell Transplantation Improves Right Ventricular Function in Patients with Nonischemic Dilated Cardiomyopathy

We investigated the effects of CD34+ cell therapy on right ventricular (RV) function in patients with nonischemic dilated cardiomyopathy (DCM). We enrolled 60 patients with DCM who were randomized to CD34+ cell therapy (Stem Cells (SC) Group n = 30), or no cell therapy (Controls, n = 30). The SC Group received granulocyte‐colony stimulating factor, and CD34+ cells were collected by apheresis and injected transendocardially. Patients were followed for 6 months. At baseline, the groups did not differ in age, gender, left ventricular ejection fraction, N‐terminal probrain natriuretic peptide, or parameters of RV function. At 6 months, we found a significant improvement in RV function in the SC Group (tricuspid annular plane systolic excursion [TAPSE]: +0.44 ± 0.64 cm, p = .001; peak systolic tissue Doppler velocity of tricuspid annulus [St]: +1.5 ± 2.1 cm/s; p = .001; percent of fractional area change [FAC]: +8.6% ± 5%, p = .01), but not in Controls (TAPSE: −0.07 ± 0.32 cm, p = .40; St: −0.1 ± 1.2 cm/s; p = .44; FAC: −1.2% ± 3.2%, p = .50). On repeat electroanatomical mapping, we found an improvement in interventricular septum viability in 19 of 30 patients from the SC Group; this correlated with the improvements in RV function (13/19 in the improved septum group versus 3/11 in the remaining cohort, p = .029). These results suggest that patients with DCM, changes in RV function correlate with changes of viability of interventricular septum. CD34+ cell therapy appears to be associated with improved right ventricular function in this patient cohort. (Clinical Trial Registration Information: www.clinicaltrials.gov; NCT02248532). Stem Cells Translational Medicine 2018;7:168–172

Establishment of Mouse Model of H-2 Haploidentical Hematopoietic Stem Cell Transplantation from Double Donors

To establish a new mouse model of H-2 haploidentical stem cell transplantation from double donors (DHSCT) and compare with conventional haploidentical hematopoietic stem cell transplantation (HSCT) so as to alleviate transplant-related complications. The recipients CB6F1 of conventional HSCT group were pretreated by 8 Gy total body irradiation(TBI), and received 3×107 donor (male C57) spleen mononuclear cells (spMNC) mobilized by G-CSF within 2 hours after TBI. Recipients CB6F1 of D-HSCT groups accepted 2 Gy TBI, and received total 12×107 spMNC mobilized by G-CSF from 2 donors within 2 hours after TBI, each donor donated 6×107 cells. According to the different strains and sex of donors, DHSCT were divided into 3 groups: in group A, the stem cells were from male C57 and female BALB/c; in group B, stem cells were from male C57 and male BALB/c, while the stem cells in group C were from male C57 and male C3H. Hematopoietic reconstruction, engraftment, GVHD and survival were observed among these 4 groups. The nadir of white blood cell count after conventional HSCT were lower than 1×109/L and lasted for 3 to 5 days, while not less than 3×109/L after D-HSCT among either group A, B or C. The complete chimerism (CC) in conventional HSCT group was achieved quickly within only 1 week in peripheral blood. Mixed chimerism (MC) in peripheral blood was found within the first week after DHSCT among either group A, B or C, and transformed into stable CC within the second week eventually. Both GVHD morbidity and mortality of conventional HSCT were 100% at 34th day after transplantation.Among DHSCT groups,the overall GVHD morbidity and mortality at 34th day after transplant were 49.6% and 50%(P<0.01,P<0.05), respectively,and 60.4% and 81.2% at 50th day after transplant. Overall survival of 50 days was 50.9% that indicated a long survival in such mice DHSCT. The differences of hematopoietic reconstruction, donor cell engraftment, GVHD incidence, GVHD mortality and OS were not statistically significant among group A, B and C(P>0.05). A new mouse model of H-2 haploidentical peripheral blood stem cell transplantation from double donors (DHSCT) has been successfully established by reducing conditioning intensity and increasing graft cell numbers from double haploidentical donors without GVHD prophylaxis. DHSCT successfully achieved stable complete chimerism, less GVHD morbidity and mortality and longer OS without hematopoietic suppression. This study provides experimental evidence for clinical application of HLA haploidentical peripheral blood stem cell transplantation from double donors.

Stem cells and necrotizing enterocolitis: A direct comparison of the efficacy of multiple types of stem cells

PurposeNecrotizing enterocolitis (NEC) is a leading cause of gastrointestinal morbidity and mortality in premature infants. While studies have shown potential for stem cell (SC) therapy in experimental NEC, no study has compared different SC side-by-side. Our purpose was to determine whether one type of SC may more effectively treat NEC than others. MethodsFour SC were compared: (1) amniotic fluid-derived mesenchymal SC (AF-MSC); (2) amniotic fluid-derived neural SC (AF-NSC); (3) bone marrow-derived mesenchymal SC (BM-MSC); and (4) neonatal enteric neural SC (E-NSC). Using an established rat model of NEC, pups delivered prematurely received an intraperitoneal injection of SC. Control pups were injected with PBS. Additional controls were breast-fed by surrogates and not subjected to experimental NEC. Intestinal tissue was graded histologically. ResultsNEC incidence was: PBS, 61.3%; breast-fed unstressed, 0%; AF-MSC, 19.1%; BM-MSC, 22.9%; AF-NSC, 18.9%; E-NSC 22.2%. All groups demonstrated statistical significance (p<0.05) compared to controls, and there was no difference between SC groups. ConclusionAll four SC groups reduced the incidence and severity of experimental NEC equivalently. AF-MSC may be preferable because of availability of AF at delivery and ease of expansion, increasing potential for clinical translation. Level of EvidenceV (Animal study).

Effect of Erythropoietin and Stem Cells on Traumatic Brain Injury

To investigate the healing effects of erythropoietin (EPO) and stem cells (SCs) in traumatic brain injury (TBI). Twenty-nine Wistar albino rats were used and separated into the following groups: control (C), EPO, SC, and SC+EPO. Group C received a TBI only, with no treatment. In the EPO group, 1000 U/kg EPO was given intraperitoneally at 30 minutes after TBI. In SC group, immediately after formation of TBI, 3× 10,000 CD34(+) stem cells were injected into the affected area. In the SC+EPO group, half an hour after TBI and the injection of stem cells, 1000 U/kg EPO was injected. Before and after injury, trauma coordination performance was measured by the rotarod and inclined plane tests. Seven weeks after trauma, rat brains were examined by radiology and histology. Rotarod performance test did not change remarkably, even after the injury. Compared with group C, the SC+EPO group was found to have significant differences in the inclined plane test results. Separately given, SCs and EPO have a positive effect on TBI, and our findings suggest that their coadministration is even more powerful.

Iron Oxide Nanoparticles Reduced Retinoic Acid Induced-neuronal Differentiation of Mouse Embryonic Stem Cells By ROS Generation.

In recent years the increasing use of nanoparticles has led researchers to study their effects on biological systems. The most important effects of nanoparticles on cells are their ability to induce or suppress production of reactive oxygen species (ROS). Changes in reactive oxygen species play an important role in various developmental processes, including proliferation and differentiation in several diseases such as Parkinson. The aim of this study was to investigate the effect of iron oxide nanoparticle with dimensions of less than 20 nanometers on the viability and neuronal differentiation of mouse embryonic stem cell (Royan B1). To assess the effects of Fe2O3 nanoparticles on neuronal differentiation of Royan B1 cells, embryoid bodies were divided into eight groups receiving different amounts of nanoparticle (10, 20, 30 μg/mL) for 12 hours, retinoic acid (1 μM), and both. Differentiation was examined under phase contrast microscope and using immunocytochemistry. Data analysis showed that cell death was increased by a time and concentration manner and there was a direct relevance between iron oxide amount and H2O2 level in cells. Statistical analysis of embryoid bodies showed that neural differentiation of mouse embryonic stem cells in groups that received nanoparticles were significantly lower than other groups and their viability were considerably reduced. According to the findings of this study it can be concluded that iron oxide nanoparticles reduce retinoic acid-neuronal differentiation in mouse embryonic stem cells and it seems that the main mechanism involved in the reduction of viability and neural differentiation was enhanced levels of ROS within the cells.

The role of the bi-compartmental stem cell niche in delaying cancer

In recent years, by using modern imaging techniques, scientists have found evidence of collaboration between different types of stem cells (SCs), and proposed a bi-compartmental organization of the SC niche. Here we create a class of stochastic models to simulate the dynamics of such a heterogeneous SC niche. We consider two SC groups: the border compartment, S1, is in direct contact with transit-amplifying (TA) cells, and the central compartment, S2, is hierarchically upstream from S1. The S1 SCs differentiate or divide asymmetrically when the tissue needs TA cells. Both groups proliferate when the tissue requires SCs (thus maintaining homeostasis). There is an influx of S2 cells into the border compartment, either by migration, or by proliferation. We examine this model in the context of double-hit mutant generation, which is a rate-limiting step in the development of many cancers. We discover that this type of a cooperative pattern in the stem niche with two compartments leads to a significantly smaller rate of double-hit mutant production compared with a homogeneous, one-compartmental SC niche. Furthermore, the minimum probability of double-hit mutant generation corresponds to purely symmetric division of SCs, consistent with the literature. Finally, the optimal architecture (which minimizes the rate of double-hit mutant production) requires a large proliferation rate of S1 cells along with a small, but non-zero, proliferation rate of S2 cells. This result is remarkably similar to the niche structure described recently by several authors, where one of the two SC compartments was found more actively engaged in tissue homeostasis and turnover, while the other was characterized by higher levels of quiescence (but contributed strongly to injury recovery). Both numerical and analytical results are presented.

Bone marrow mesenchymal stem cell and vein conduit on sciatic nerve repair in rats.

Background:Peripheral nerve repair with sufficient functional recovery is an important issue in reconstructive surgery. Stem cells have attracted extensive research interest in recent years.Objectives:The purpose of this study was to compare the vein conduit technique, with and without the addition of mesenchymal stem cells in gap-less nerve injury repair in rats.Materials and Methods:In this study, 36 Wistar rats were randomly allocated to three groups: In the first group, nerve repair was performed with simple neurorrhaphy (control group), in the second group, nerve repair was done with vein conduit over site (vein conduit group) and in the third group, bone marrow stem cells were instilled into the vein conduit (stem cell group) after nerve repair with vein conduit over site. Six weeks after the intervention, the sciatic function index, electrophysiological study and histological examination were performed.Results:All animals tolerated the surgical procedures and survived well. The sciatic function index and latency were significantly improved in the vein conduit (P = 0.04 and 0.03, respectively) and stem cell group (P = 0.02 and 0.03, respectively) compared with the control group. No significant difference was observed in sciatic function and latency between the vein conduit and stem-cell groups. Moreover, histological analysis showed no significant difference in regenerative density between these two groups.Conclusions:The results of this study showed that the meticulous microsurgical nerve repair, which was performed using the vein tubulization induced significantly better sciatic nerve regeneration. However, the addition of bone marrow mesenchymal stem cell to vein conduit failed to promote any significant changes in regeneration outcome.

Effect of myogenic stem cells on the integrity and histomorphology of repaired transected external anal sphincter

The objective was to evaluate the effect of myogenic stem cells on histological properties and the volume of striated muscle of the external anal sphincter after transection and repair. Histological analysis was performed on the external anal sphincters of 40 young female rats euthanized at 7 or 90 days after transection and repair and randomization to injection of either phosphate buffered solution (PBS) or myogenic stem cells (SC) at the transection site. Sphincter complexes, previously evaluated for neurophysiological function, were processed for histology and analyzed for possible disruption, amount of inflammation, and volume of striated muscle. The relationship between the muscular disruption and contractile force of sphincters was evaluated. Disruption was seen in 100 % of sphincters 7 days after repair for both SC and control animals. Eighty-nine percent of controls and 78% of SC-administered animals had intact sphincters at 90 days. Significant inflammatory infiltrate was seen in repaired anal sphincters for both the PBS and the SC groups at 7 days, and persisted at 90 days, with no difference between treatment groups. Striated muscle volume increased from 7 to 90 days for both control and SC-administered animals. Although there was no difference in volume between treatments, there was substantial temporal improvement in contractile force generation of the sphincters receiving SC compared with those receiving PBS. In this animal model, administration of myogenic stem cells to transected/repaired anal sphincters did not alter the amount of inflammation nor the volume of striated muscle, suggesting that stem cells might improve contractile function through other cellular processes.

Intracoronary Infusion of Mononuclear Bone Marrow-Derived Stem Cells is Associated with a Lower Plaque Burden After Four Years

To assess the long-term effects of intracoronary stem cell (SC) infusion following acute myocardial infarction (AMI) on the local atherosclerotic process at the site of infusion after four years of follow-up. We evaluated 18 post-AMI patients. Group 1 consisted of nine patients given an intracoronary injection of autologous mononuclear SC, and group 2 consisted of nine patients given a placebo injection. The plaque count, plaque burden (PB) and coronary calcium score (CCS) were assessed using multislice 64 CT angiography of the coronary tree four years after SC injection. The total PB and CCS along the entire coronary segment distal to the site of infusion were significantly lower in the SC group (PB-702 mm(3) vs. 1.465 mm(3), p=0.0006; CCS-295 vs. 796, p＜ 0.0001).The mean PB per coronary artery was 112.12 mm(3)±16.82 mm(3) for the treated arteries vs. 189.56 mm(3)±20.98 mm(3) for the untreated arteries (p＜0.0001), while the mean CCS was 53.12±16.4 vs. 106.43±10.86 (p＜0.0001). In the SC group, there were significant differences in the mean PB (87.75 mm(3) vs. 112.12 mm(2), p= 0.005) and mean CCS (36.87 vs. 53.12, p=0.04) between the coronary segment infused with SC and the entire coronary artery. Multislice CT angiography of atheromatous plaques in the coronary tree four years after SC infusion in post-AMI patients indicates a significantly lower atheromatous plaque burden, as demonstrated by a lower plaque volume and lower CCS at the site of stem cell infusion compared with other coronary territories.

Primo Vascular System: Past, Present, and Future

Primo Vascular System: Past, Present, and Future