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1.
ZAHRA KALHORI MEHRI AZADBAKHT MALEK SOLEIMANI MEHRANJANI MOHAMMAD ALI SHARIATZADEH 《Cytotherapy》2018,20(12):1445-1458
Background
Many studies have reported that inflammation and oxidative stress are involved in the pathogenesis of polycystic ovary syndrome (PCOS). Bone marrow mesenchymal stromal cells (BM-MSCs) have anti-oxidant and anti-inflammation properties. In this study, we investigate the beneficial effect of stem cell therapy on folliculogenesis in mice with induced PCOSMethods
Mouse model of PCOS was performed through daily injection of testosterone enanthate (1 mg/100 g/body weight subcutaneous (s.c).) for a period of 5 weeks. Naval Medical Research Institute (NMRI) mice (21 days old) were divided into three groups: control, PCOS and PCOS?+?BM-MSCs. BM-MSCs were labeled with Hoechst 33342 (0.5 µg/mL) and then injected into the mice (106/animal, via the tail vein) at 1 and 14 days after PCOS confirmation. Mice were humanely killed at 2 weeks after last transplantation. Ovarian stereological studies were done. Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), testosterone, interleukin (IL)-6 and tumor necrosis factor (TNF)-α serum levels were measured. The levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum were analyzed. Apoptotic index for ovarian follicles was assessed using Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). CD31 expression in ovarian vessels was assessed with the immunohistochemistry.Results
There was a significant increase in the total volume of ovary, cortex, number of antral follicles, volume of oocyte and zona pellucida thickness, and there was a significant decrease in the primary and preantral follicles number in the PCOS?+?BM-MSCs group compared with the PCOS group. There was a significant increase in the serum level of FSH and TAC and a significant decrease in the serum level of testosterone, LH, MDA and percentage of TUNEL-positive apoptotic cells in the PCOS?+?BM-MSCs group in comparison with the PCOS group.Discussion
BM-MSC transplantation improves folliculogenesis in mice with induced PCOS. BM-MSC therapy can be an operative treatment for PCOS via anti-inflammatory, anti-oxidant and anti-apoptotic properties. 相似文献2.
Chloe L. Rackham Stefan Amisten Shanta J. Persaud Aileen J.F. King Peter M. Jones 《Cytotherapy》2018,20(12):1427-1436
Background aims
Mesenchymal stromal cells (MSCs) enhance islet function both in vitro and in vivo, at least in part by secreting ligands that activate islet G-protein coupled receptors (GPCRs). We assessed whether pre-treatment with a defined “cocktail” of MSC-secreted GPCR ligands enhances islet functional survival in vitro and improves the outcomes of islet transplantation in an experimental model of diabetes.Methods
Isolated islets were cultured for 48 h with ANXA1, SDF-1 or C3a, alone or in combination. Glucose-stimulated insulin secretion (GSIS) and cytokine-induced apoptosis were measured immediately after the 48 h culture period and at 24 h or 72 h following removal of the ligands from the culture media. Islets were syngeneically transplanted underneath the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice and blood glucose levels monitored for 28 days.Results
Pre-culturing islets with a cocktail of ANXA1/SDF-1/C3a potentiated GSIS and protected islet cells from cytokine-induced apoptosis in vitro. These effects were maintained for up to 72 h after the removal of the factors from the culture medium, suggesting a sustained protection of islet graft functional survival during the immediate post-transplantation period. Islets pre-treated with the cocktail of MSC secretory factors were more effective in reducing blood glucose in diabetic mice, consistent with their improved functional survival in vivo.Discussion
Pre-culturing islets with a cocktail of MSC secretory products offers a well-defined, cell-free approach to improve clinical islet transplantation outcomes while avoiding many of the safety, regulatory and logistical hurdles of incorporating MSCs into transplantation protocols. 相似文献3.
Mona Navaei-Nigjeh Milad Moloudizargari Maryam Baeeri Mahdi Gholami Nasrin Lotfibakhshaiesh Masoud Soleimani Ebrahim Vasheghani-farahani Jafar AI Mohammad Abdollahi 《Cytotherapy》2018,20(9):1124-1142
Background aims
Adipose tissue–derived mesenchymal stromal cells (AT-MSCs), widely known as multipotent progenitors, release several cytokines that support cell survival and repair. There are in vitro and in vivo studies reporting the regenerative role of AT-MSCs possibly mediated by their protective effects on functional islet cells as well as their capacity to differentiate into insulin-producing cells (IPCs).Methods
On such a basis, our goal in the present study was to use three different models including direct and indirect co-cultures and islet-derived conditioned medium (CM) to differentiate AT-MSCs into IPCs and to illuminate the molecular mechanisms of the beneficial impact of AT-MSCs on pancreatic islet functionality. Furthermore, we combined in vitro co-culture of islets and AT-MSCs with in vivo assessment of islet graft function to assess whether co-transplantation of islets with AT-MSCs can reduce marginal mass required for successful islet transplantation and prolong graft function in a diabetic rat model.Results
Our findings demonstrated that AT-MSCs are suitable for creating a microenvironment favorable for the repair and longevity of the pancreas β cells through the improvement of islet survival and maintenance of cell morphology and insulin secretion due to their potent properties in differentiation. Most importantly, hybrid transplantation of islets with AT-MSCs significantly promoted survival, engraftment and insulin-producing function of the graft and reduced the islet mass required for reversal of diabetes.Conclusions
This strategy might be of therapeutic potential solving the problem of donor islet material loss that currently limits the application of allogeneic islet transplantation as a more widespread therapy for type 1 diabetes. 相似文献4.
MAHINDER Paul DEVI DAYAL ANIL BHANSALI LAKHBIR DHALIWAL NARESH SACHDEVA 《Cytotherapy》2018,20(11):1355-1370
Background
Antigen-specific regulatory T cells (Tregs) have proven to be effective in reversing established autoimmunity in type 1 diabetes (T1D). Cord blood (CB) can serve as an efficient and safe source for Tregs for antigen-specific immunomodulation in T1D, a strategy that is yet to be explored. Therefore, we assessed the potential of CB in generation of proinsulin (PI)-specific Tregs by using HLA class II tetramers.Methods
We analyzed the frequency of PI-specific natural Tregs (nTregs) and induced Tregs (iTregs) derived from the CB as well as peripheral blood (PB) of patients with T1D and healthy control subjects. For this, CD4+CD25+CD127low and CD4+CD25-T cells were cultured in the presence of PI-derived peptides, transforming growth factor (TGF)-β and rapamycin. PI-specific Tregs were then selected using allele-specific HLA II tetramers loaded with PI-derived peptides, followed by suppression assays.Results
Following stimulation, we observed that CB harbors a significantly higher frequency of PI-specific Tregs than PB of subjects with T1D (P?=?0.0003). Further, the proportion of PI-specific Tregs was significantly higher in both the nTreg (P?=?0.01) and iTreg (P?=?0.0003) compartments of CB as compared with PB of subjects with T1D. In co-culture experiments, the PI-specific Tregs suppressed the proliferation of effector T cells significantly (P?=?0.0006). The expanded nTregs were able to retain hypomethylation status at their Tregs-specific demethylated region (TSDR), whereas iTregs were unable to acquire the characteristic demethylation pattern.Conclusion
Our study demonstrates that CB can serve as an excellent source for generation of functional antigen-specific Tregs for immunotherapeutic approaches in subjects with T1D. 相似文献5.
Alann Thaffarell Portilho Souza Gileade Pereira Freitas Helena Bacha Lopes Emanuela Prado Ferraz Fabiola Singaretti Oliveira Marcio Mateus Beloti Adalberto Luiz Rosa 《Cytotherapy》2018,20(10):1267-1277
Background aims
Regenerative medicine strategies based on cell therapy are considered a promising approach to repair bone defects. The aims of this study were to evaluate the effect of subculturing on the osteogenic potential of osteoblasts derived from newborn rat calvaria and the effect of these osteoblasts on bone repair of rat calvaria defects.Methods
Cells were obtained from 50 newborn rat calvaria, and primary osteoblasts (OB) were compared with first passage (OB-P1) in terms of osteogenic potential by assaying cell proliferation, alkaline phosphatase (ALP) activity, extracellular matrix mineralization and gene expression of the osteoblastic markers RUNX2, ALP, osteocalcin and bone sialoprotein. Then, 5-mm calvaria defects were created in 24 Wistar rats, and after 2 weeks, they were locally injected with 50 µL of phosphate-buffered saline containing either 5?×?106 osteoblasts (OB-P1, n?=?12) or no cells (control, n?=?12). Four weeks post-injection, the bone formation was evaluated by micro-computed tomography and histological analyses. Data were compared by analysis of variance, followed by the Student-Newman-Keuls's test or Student's t-test (P ≤ 0.05).Results
OB-P1 showed high proliferation and ALP activity, and despite the reduced gene expression of osteoblastic markers and extracellular matrix mineralization compared with OB, they displayed osteogenic potential, being a good choice for injection into calvaria defects. The micro-tomographic and histological data showed that defects treated with OB-P1 presented higher bone formation compared with control defects.Discussion
Our results indicate that cells derived from newborn rat calvaria retain osteoblastic characteristics after subculturing and that these osteoblasts stimulate bone repair in a rat calvaria defect model. 相似文献6.
ILARIA ZOLLINO DIANA CAMPIONI MARIA GRAZIA SIBILLA MIRKO TESSARI ANNA MARIA MALAGONI PAOLO ZAMBONI 《Cytotherapy》2019,21(2):200-211
Background aims
Preclinical and observational reports indicate that adipose tissue (AT) is a safe and promising tool to treat non-healing venous leg ulcers (VLUs).Methods
From an initial cohort of 38 patients, 16 patients affected by non-healing VLUs were randomly allocated to the experimental arm (5 men and 3 women) and control arm (5 men and 3 women). In the experimental arm, wounds were treated by debridement, centrifuged adipose tissue (CAT), advanced dressings and compression. No experimental treatment (CAT) was administered to the control arm. We investigated the functional and the immunophenotypical features of the harvested CAT-derived stem cells. The primary outcome measures were healing time and safety of the cell treatment. Secondary outcomes were pain evaluated by numeric rating scale (NRS), complete wound healing at 24 weeks by Margolis Index and wound-healing process expressed in square centimeters per week. The various immunophenotypic and functional characteristics of CAT-derived stem cells were then correlated with the clinical outcomes.Results
No major adverse events were recorded. The healing time was significantly faster by applying CAT, 17.5 ± 7.0 weeks versus 24.5 ± 4.9 weeks recorded in the control arm (P < 0.036). NRS dropped after the first week to 2.7 ± 2.0 in the experimental arm versus 6.6 ± 3.0 in the control group (P < 0.01). The rate of healing at the 24th week was not significantly different between arms. Interestingly, we found a strong reverse correlation between the percent of CD34+/CD45– non-hematopoietic cells, respectively, with the healing time (r?=?–0.894, P < 0.041) and NRS (r?=?–0.934, P < 0.020).Conclusions
CAT is safe and may accelerate healing time in VLUs as well as reduce wound pain. The percentage of CD34+/CD45– cells in stromal vascular fraction (SVF) seems to be a predictive biomarker of successful CAT treatment in these patients. 相似文献7.
FABIANY DA COSTA GONÇALVES MICHELE ARAMBURU SERAFINI HELENA FLORES MELLO BIANCA PFAFFENSELLER ANELISE BERGMANN ARAÚJO FERNANDA VISIOLI ANA HELENA PAZ 《Cytotherapy》2018,20(12):1459-1471
Background aims
Although mesenchymal stromal cells (MSCs) have shown therapeutic potential in intestinal tissue repair, controversy concerning their short survival and poor biodistribution in recipient tissues still remains. Therefore, we investigated the paracrine role of MSC in three-dimensional culture of colon with experimental colitis.Methods
Colitis was induced in mice by oral administration of dextran sulfate sodium (DSS) for 7 days. Inflammatory responses were assessed on the basis of clinical signs, morphological, and histopathological parameters. On days 2 and 5, colonic explants were removed, and a three-dimensional culture was performed. The structural integrity of the intestinal mucosa was tested by treating the cultures with MSC or conditioned medium (CM) for 24 h, and then the colons were analyzed for histology/immunohistochemistry and interleukin (IL)-6 production.Results
Histological analysis demonstrated that both MSC and CM treatment reduced colon damage in organ culture. An increase in cell proliferation (Ki-67 staining) was observed after CM treatment. Additionally, MSC treatment was able to reduce CD3+ cells. The therapeutic effect of MSC and CM was mediated by the downregulation of IL-6.Discussion
The intestinal in vitro model has shown to be potentially useful for studying cellular interactions in a three-dimensional cell arrangement. Moreover, our results provide strong evidence that both MSC and CM treatments can alleviate colonic damage in organ culture. Importantly, these results suggest that MSC-secreted factors are able to protect the colon from inflammation caused by DSS-induced colitis independent of cell transplantation. 相似文献8.
CONG CHEN YIN-HUA MA YA-TING ZHANG FAN ZHANG NING ZHOU XIANG WANG TAO LIU YU-MIN LI 《Cytotherapy》2018,20(8):975-989
Background aims
Dendritic cell (DC)-based immunotherapy has recently been reported frequently in the treatment of hepatocellular carcinoma (HCC); however, its efficacy remains controversial. In this study, we aimed to evaluate the clinical efficacy of DC-based immunotherapy on HCC by conducting a systematic review and meta-analysis.Methods
PubMed, Cochrane Library, Embase and Web of Science were searched to identify clinical trials on DC-based immunotherapy for HCC published up to January 31, 2018. The articles were selected according to pre-established inclusion criteria and methodologic quality, and publication bias were evaluated.Results
A total of 1276 cases from 19 clinical trials were included. Compared with traditional treatment, further DC-based therapy enhanced the CD4+ T/CD8+ T ratio (standardized mean difference: 0.68, 95% confidence interval [CI] 0.46–0.89, P < 0.001); increased the 1-year, 18-month and 5-year progression-free survival (PFS) rate and the 1-year, 18-month and 2-year overall survival (OS) rate (relative risk > 1, P < 0.05), prolonged the median PFS time (median survival ratio [MSR]: 1.98, 95% CI: 1.60–2.46, P < 0.001) and median OS time (MSR: 1.72, 95% CI: 1.51–1.96, P < 0.001). Adverse reactions were mild.Conclusions
DC-based therapy not only enhanced anti-tumor immunity, improved the survival rate and prolonged the survival time of HCC patients, but it was also safe. These findings will provide encouraging information for further development of DC-based immunotherapy as an adjuvant treatment for HCC. However, the results must be interpreted with caution because of the small study numbers, publication bias and the various of study designs, pre-treatment and therapeutic processes of DCs. 相似文献9.
ABEL TRUJILLO-OCAMPO HYUN-WOO CHO AMANDA C. HERRMANN WILFREDO RUIZ-VAZQUEZ ANDREW B. THORNTON HONG HE DAN LI MARIAM A. QAZILBASH QING MA STEVEN A. PORCELLI ELIZABETH J. SHPALL JEFFREY MOLLDREM JIN S. IM 《Cytotherapy》2018,20(8):1089-1101
Background aims
CD1d-restricted invariant natural killer (iNK) T cells are rare regulatory T cells that may contribute to the immune-regulation in allogeneic stem cell transplantation (ASCT). Here, we sought to develop an effective strategy to expand human iNK T cells for use in cell therapy to prevent graft-versus-host disease (GVHD) in ASCT.Methods
Human iNK T cells were first enriched from peripheral blood mononuclear cells (PBMCs) using magnetic-activated cell sorting separation, then co-cultured with dendritic cells in the presence of agonist glycolipids, alpha-galactosylceramide, for 2 weeks.Results
The single antigenic stimulation reliably expanded iNK T cells to an average of 2.8?×?107 per 5?×?108 PBMCs in an average purity of 98.8% in 2 weeks (N?=?24). The expanded iNK T cells contained a significantly higher level of CD4+ and central memory phenotype (CD45RA?CD62L+) compared with freshly isolated iNK T cells, and maintained their ability to produce both Th-1 (interferon [IFN]γ and tumor necrosis factor [TNF]α) and Th-2 type cytokines (interleukin [IL]-4, IL-5 and IL-13) upon antigenic stimulation or stimulation with Phorbol 12-myristate 13-acetate/ionomycin. Interestingly, expanded iNK T cells were highly autoreactive and produced a Th-2 polarized cytokine production profile after being co-cultured with dendritic cells alone without exogenous agonist glycolipid antigen. Lastly, expanded iNK T cells suppressed conventional T-cell proliferation and ameliorated xenograft GVHD (hazard ratio, 0.1266; P < 0.0001).Conclusion
We have demonstrated a feasible approach for obtaining ex vivo expanded, highly enriched human iNK T cells for use in adoptive cell therapy to prevent GVHD in ASCT. 相似文献10.
REBECCA M. Harman MEGAN K. HE SHENG ZHANG GERLINDE R. VAN DE WALLE 《Cytotherapy》2018,20(8):1061-1076
Background
Impaired cutaneous wound healing is common in humans, and treatments are often ineffective. Based on the significant emotional and economic burden of impaired wound healing, innovative therapies are needed. The potential of mesenchymal stromal cell (MSC)–secreted factors to treat cutaneous wounds is an active area of research that is in need of refinement before effective clinical trials can be initiated. The aims of the present study were to (i) study which MSC-secreted factors stimulate dermal fibroblast (DF) migration in vitro and (ii) evaluate the potential of these factors to promote wound healing in vivo.Methods
To this end, MSCs were isolated from the peripheral blood of healthy horses, a physiologically relevant large animal model appropriate for translational wound-healing studies. Conditioned medium (CM) from cultured equine MSCs was analyzed using liquid chromatography-mass spectrophotometry (LC-MS/MS) to identify secreted proteins of interest. Double-stranded RNA-mediated interference (RNAi) was used to silence the genes encoding selected proteins, and the effects of CM from these transfected MSCs on migration of cultured equine DF cells in vitro and full-thickness wounds in mice were evaluated.Results
We found that MSC-derived plasminogen activator inhibitor-1 (PAI-1) and tenascin-C significantly increased DF migration in vitro and improved wound healing in vivo by decreasing time to wound closure.Discussion
These results suggest that in a complex wound environment, MSC-secreted factors PAI-1 and tenascin-C contribute to the positive effect of therapeutically applied MSC CM on wound healing. 相似文献11.
MATTHEW LI LING-YEE CHIN SYUKRI SHUKOR ALFRED TAMAYO MARCELA V. MAUS BIJU PAREKKADAN 《Cytotherapy》2019,21(1):76-82
Background aim
Translation of therapeutic cell therapies to clinical-scale products is critical to realizing widespread success. Currently, however, there are limited tools that are accessible at the research level and readily scalable to clinical-scale needs.Methods
We herein developed and assessed a closed loop bioreactor system in which (i) a highly gas-permeable silicone material was used to fabricate cell culture bags and (ii) dynamic flow was introduced to allow for dissociation of activated T-cell aggregates.Results
Using this system, we find superior T-cell proliferation compared with conventional bag materials and flasks, especially at later time points. Furthermore, intermittent dynamic flow could easily break apart T-cell clusters.Conclusions
Our novel closed loop bioreactor system is amenable to enhanced T-cell proliferation and has broader implications for being easily scaled for use in larger need settings. 相似文献12.
Background
Neo-vascularization, an indispensible phenomenon for tissue regeneration, facilitates repair and remodeling of wound tissues. This process is impaired in chronic wounds due to reduced number and recruitment of endothelial cells (ECs), thereby necessitating development of newer strategies to enhance the EC repertoire as a therapeutic approach.Methods
We explored the ‘plasticity’ of Wharton's jelly derived–mesenchymal stromal cells (WJ-MSCs) using an anti-inflammatory drug-mediated enhanced trans-differentiation into ECs, based on our observation of temporal decrease in COX-2 expression during trans-differentiation of MSCs into ECs at day 7 and 14 along with mature ECs.Results
At a physiological level, an increased DiI-labeled acetylated-low density lipoprotein (DiI-Ac-LDL) uptake, proliferation, migration and chick chorio allantoic membrane (CAM)-vasculogenesis occurred while at a molecular level significant up-regulation in messenger RNA (mRNA) and protein expression of endothelial-specific markers, Vegfr2, Pecam, eNOS, VE-Cadh and Tie-2, along with an activated p-VEGFR2 and its downstream mediators were observed in celecoxib-preconditioned ECs as compared with WJ-MSCs. Green fluorescent protein (GFP)-expressing stable WJ-MSCs and trans-differentiated EC-D14 in the absence/presence of celecoxib were generated using antibiotic selection for intradermal transplantation at the wound site on a murine ‘excisional splinting wound’ model. Engraftment of transplanted human cells in immunosuppressant-treated mice was confirmed by a significant increase in the expression levels of human gene-specific endothelial markers at the regenerated wound sites. Morphometrically, increased vascularity and percent wound closure were observed in regenerated wounds of mice transplanted with celecoxib-preconditioned-EC-D14.Conclusion
Cox-2 inhibition led to an enhanced trans-differentiation of WJ-MSCs into ECs that, when transplanted, accelerated the skin regeneration by engraftment and neo-vascularization at the wound bed, suggesting a plausible new therapeutic role of celecoxib. 相似文献13.
GABRIELA OTERO CAROLINE AGORIO ALEXANDRA SUJANOV LOURDES ECHARTE ANA TCHEKMEDYIAN MONICA MONTELONGO ALBA MENYOU ANDRES RODRIGUEZ LILIAN DIAZ ISMAEL RODRIGUEZ CRISTINA TOURIÑO 《Cytotherapy》2019,21(2):189-199
Background
Chronic venous leg ulcers (VLUs) are a common problem in clinical practice and available treatments are not satisfactory. The use of adjuvant therapies in combination with lower limb compression may lead to improved healing rates. Chronic wounds are candidates for new strategies in the emergent field of regenerative medicine. Bone marrow–derived cells (BMDCs) contain cells and secrete cytokines known to participate in wound healing. Thus, BMDC therapy seems a logical strategy for the treatment of chronic wounds. Our objective was to evaluate feasibility, safety and initial clinical outcome of autologous BMDC therapy associated with standard treatment in patients with VLUs.Methods
We conducted an open-label, single-arm, prospective pilot clinical trial in four patients with six chronic VLUs. The study protocol was approved by the institutional and national review boards and ethics committees. Bone marrow was harvest, processed and then administered by multiple injections into the ulcers. All patients received standard treatment and non-healing characteristics of the VLUs were confirmed at study entry.Results
Ulcer size and wound pain evaluated 12 months after BMDC treatment were significantly reduced (P < 0.05). BMDC treatment was safe and well tolerated in long-term follow-up.Discussion
Despite the low number of patients studied, our results showed that autologous BMDC treatment could be a useful, feasible and safe procedure to enhance ulcer healing. However, randomized controlled trials with more patients are needed to address this question and translate this approach into clinical practice. 相似文献14.
TZUHUA LIN JUKKA PAJARINEN YUSUKE KOHNO MASAHIRO MARUYAMA MONICA ROMERO-LOPEZ JHIH-FONG HUANG KARTHIK NATHAN TAHSIN N. KHAN ZHENYU YAO STUART B. GOODMAN 《Cytotherapy》2018,20(8):1028-1036
Background
Mesenchymal stromal cell (MSC)–based therapy has great potential to modulate chronic inflammation and enhance tissue regeneration. Crosstalk between MSC-lineage cells and polarized macrophages is critical for bone formation and remodeling in inflammatory bone diseases. However, the translational application of this interaction is limited by the short-term viability of MSCs after cell transplantation.Methods
Three types of genetically modified (GM) MSCs were created: (1) luciferase-expressing reporter MSCs; (2) MSCs that secrete interleukin (IL)-4 either constitutively; and (3) MSCs that secrete IL-4 as a response to nuclear factor kappa-light-chain-enhancer of activated B cell (NFκB) activation. Cells were injected into the murine distal femoral bone marrow cavity. MSC viability and bone formation were examined in vivo. Cytokine secretion was determined in a femoral explant organ culture model.Results
The reporter MSCs survived up to 4 weeks post-implantation. No difference in the number of viable cells was found between high (2.5?×?106) and low (0.5?×?106) cell-injected groups. Injection of 2.5?×?106 reporter MSCs increased local bone mineral density at 4 weeks post-implantation. Injection of 0.5?×?106 constitutive IL-4 or NFκB-sensing IL-4–secreting MSCs increased bone mineral density at 2 weeks post-implantation. In the femoral explant organ culture model, LPS treatment induced IL-4 secretion in the NFκB-sensing IL-4–secreting MSC group and IL-10 secretion in all the femur samples. No significant differences in tumor necrosis factor (TNF)α and IL-1β secretion were observed between the MSC-transplanted and control groups in the explant culture.Discussion
Transplanted GM MSCs demonstrated prolonged cell viability when transplanted to a compatible niche within the bone marrow cavity. GM IL-4–secreting MSCs may have great potential to enhance bone regeneration in disorders associated with chronic inflammation. 相似文献15.
Background
We recently showed that transient warming effects decreased the functional and adhesion properties of mesenchymal stromal cells (MSC) while post-thaw viability remained high. In an attempt to better predict functional impairment of cryopreserved MSC, we further analysed the correlation between viability, immunosuppressive activity and adhesion of cells exposed or not to warming events.Methods
MSC prepared from six umbilical cords were frozen to ?130°C and immediately transferred in a dry ice container or exposed to room temperature for 2 to 10 min (warming events) prior to storage in liquid nitrogen. Viability, functionality (inhibition of T-cell proliferation), adhesion and expression of various integrins were evaluated.Results
The monotonic loss of functional activity with time was proportional to the length of warming events to which MSC were subjected and correlated with the monotonic loss of adhesion capacity. In contrast, post-thaw viability assessment did not predict functional impairment. Interestingly, flow cytometry analyses revealed the emergence of a FSClow population present in the viable cell fraction of freshly thawed MSC, which displayed poor adhesion capacity and expressed low levels of integrin β5. The prevalence of this FSClow population increased with the length of warming events and correlated with impaired functional and adhesion properties.Discussion
Our results reveal that loss of functional activity (4-day test) induced by transient warming events could be predicted by evaluating adhesion (2-hr test) or FSC profile (10-min test) of MSC immediately post-thaw. These observations could lead to the development of surrogate tests for rapidly assessing the functional quality of cryopreserved MSC. 相似文献16.
GAMZE DERELI CAN ÖZGE EKIN AKDERE MEHMET EROL CAN MENEMŞE GÜMÜŞDERELIOĞLU 《Cytotherapy》2019,21(1):83-95
Background
Several methods to cultivate limbal epithelial stem cells (LESCs) in vitro with the support of feeder layers and different growth medium formulations have been established for several years. The initial green medium consists of various ingredients that exhibit a non-optimal level of biosafety, therefore, different modifications have been made to suit it to safe clinical applications. However, the question of which formulation is the most appropriate remains to be answered.Aims
This study evaluated the outgrowth kinetics and stemness of cells cultured from human limbal explants with the aim of preserving LESC characteristics in the human-derived platelet-rich fibrin (HPRF)–conditioned medium with no feeder cell layer or carrier for the first time. The final composition of the cell culture system included only human-derived products without any xenobiotic or chemical substances to minimize the potential risk for human health, which will be useful for clinical purposes.Methods
To test our hypothesis, limbal explants were incubated with either Dulbecco's Modified Eagle's Medium (DMEM)/F12-10% human serum (HS), human-derived amniotic membrane (HAM)-conditioned DMEM/F12-10% HS or HPRF-conditioned DMEM/F12-10% HS to determine whether outgrowth kinetics and stemness of cells show any differences among groups.Results
The results showed that the HPRF-conditioned medium showed higher concentration levels of growth factors, which may be involved in the promotion of LESC expansion while preserving the stem cell characteristics. HPRF-conditioned medium had significantly superior capacity to enhance the cell growth rate, the stem/progenitor cell phenotype and the expressions of putative stem cell markers.Conclusion
This novel xeno-feeder-chemical-free, completely human-derived and biologically safe culture system including HPRF and HS would be of interest to replace conventional cell culture strategies to meet safety requirements mandatory for clinical use in humans. 相似文献17.
SHAYESTEH KHALIFEH SOLTANI BIJAN FOROGH NASER AHMADBEIGI HOMAYOUN HADIZADEH KHARAZI KHADIJEH FALLAHZADEH LADAN KASHANI MASOUMEH KARAMI YADOLLAH KHEYROLLAH MOHAMMAD VASEI 《Cytotherapy》2019,21(1):54-63
Objective
Knee osteoarthritis (OA) is a common skeletal impairment that can cause many limitations in normal life activities. Stem cell therapy has been studied for decades for its regenerative potency in various diseases. We investigated the safety and efficacy of intra-articular injection of placental mesenchymal stem cells (MSCs) in knee OA healing.Methods
In this double-blind, placebo-controlled clinical trial, 20 patients with symptomatic knee OA were randomly divided into two groups to receive intra-articular injection of either 0.5–0.6?×?108 allogenic placenta-derived MSCs or normal saline. The visual analogue scale, Knee OA Outcome Score (KOOS) questionnaire, knee flexion range of motion (ROM) and magnetic resonance arthrography were evaluated for 24 weeks post-treatment. Blood laboratory tests were performed before and 2 weeks after treatment.Results
Four patients in the MSC group showed mild effusion and increased local pain, which resolved safely within 48–72 h. In 2 weeks post-injection there was no serious adverse effect and all of the laboratory test results were unchanged. Early after treatment, there was a significant knee ROM improvement and pain reduction (effect size, 1.4). Significant improvements were seen in quality of life, activity of daily living, sport/recreational activity and decreased OA symptoms in the MSC-injected group until 8 weeks (P < 0.05). These clinical improvements were also noted in 24 weeks post-treatment but were not statistically significant. Chondral thickness was improved in about 10% of the total knee joint area in the intervention group in 24 weeks (effect size, 0.3). There was no significant healing in the medial/lateral meniscus or anterior cruciate ligament. There was no internal organ impairment at 24 weeks follow-up.Conclusion
Single intra-articular allogenic placental MSC injection in knee OA is safe and can result in clinical improvements in 24 weeks follow-up. Trial registration number: IRCT2015101823298N. 相似文献18.
Background
Multiple myeloma (MM) is a hematologic cancer caused by the abnormal expansion of plasma cells, but the exact mechanism underlying MM development is not completely known. Recently, multiple long noncoding RNAs (lncRNAs) were implicated in the regulation of MM development.Methods
Samples from patients with MM were collected and detected for LINC00461 expression using real-time polymerase chain reaction (PCR). LINC00461 was knocked down in MM cell lines by short hairpin RNAs (shRNAs) to measure its effect on MM cell proliferation and apoptosis. The function of mesenchymal stromal cell (MSC)–derived exosomes was analyzed using chamber assays.Results
LINC00461 was highly expressed in MM. Knockdown of LINC00461 dramatically reduced MM cell proliferation and induced cell apoptosis. Further study showed that LINC00461 relieved the inhibitory effect of microRNA (miR)-15a/miR-16 on BCL-2. In addition, we observed that MSC-derived exosomes promoted MM cell proliferation through LINC00461.Conclusion
Our findings demonstrate that LINC00461, a sponge for miR-15a/16, is highly expressed in MSC-derived exosomes, and enhances MM cell proliferation, which may become an excellent candidate for therapeutic applications. 相似文献19.
ROMAIN Guiho KEVIN BITEAU GIULIA GRISENDI MATHIAS CHATELAIS REGIS BRION JULIEN TAURELLE SARAH RENAULT DOMINIQUE HEYMANN MASSIMO DOMINICI FRANÇOISE REDINI 《Cytotherapy》2018,20(8):1037-1045
Background
Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor. OS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine Tumor necrosis factor (TNF)–Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, many OS cell lines appear resistant to recombinant human (rh)TRAIL-induced apoptosis. We, therefore, hypothesized that TRAIL presentation at the membrane level of carrier cells might overcome this resistance and trigger apoptosis.Methods
To address this, human adipose mesenchymal stromal cells (MSCs) transfected in a stable manner to express membrane-bound full-length human TRAIL (mbTRAIL) were co-cultured with several human OS cell lines.Results
This induced apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL. In contrast, mbTRAIL delivered by MSCs was not able to counteract tumor progression in this OS orthotopic model.Discussion
This was partly due to the fact that MSCs showed a potential to support tumor development. Moreover, the expression of mbTRAIL did not show caspase activation in adjacent tumor cells. 相似文献20.
MAMTA KALRA ULRIKE GERDEMANN JESSICA D. LUU MINTHRAN C. NGO ANN M. LEEN CHRYSTAL U. LOUIS CLIONA M. ROONEY STEPHEN GOTTSCHALK 《Cytotherapy》2019,21(2):212-223