共查询到20条相似文献，搜索用时 734 毫秒
1.
Background
Mesenchymal stromal cells (MSCs) offer great potential for diverse clinical applications. However, conventional systemic infusion of MSCs limits their therapeutic benefit, since intravenously (IV) infused cells become entrapped in the lungs where their dwell time is short.Methods
To explore possible alternatives to IV infusion, we used in vivo optical imaging to track the bio-distribution and survival of 1 million bioluminescent MSCs administered IV, intraperitoneally (IP), subcutaneously (SC) and intramuscularly (IM) in healthy athymic mice.Results
IV-infused MSCs were undetectable within days of administration, whereas MSCs implanted IP or SC were only detected for 3 to 4 weeks. In contrast, MSCs sourced from human umbilical cord matrix or bone marrow survived more than 5 months in situ when administered IM. Long-term survival was optimally achieved using low passage cells delivered IM. However, MSCs could undergo approximately 30 doublings before their dwell time was compromised. Cryo-preserved MSCs administered IM promptly after thaw were predominantly cleared after 3 days, whereas equivalent cells cultured overnight prior to implantation survived more than 3 months.Discussion
The IM route supports prolonged cell survival of both neo-natal and adult-derived MSCs, although short-term MSC survival was comparable between all tested routes up to day 3. IM implantation presents a useful alternative to achieve clinical benefits from prolonged MSC dwell time at a homeostatic implant site and is a minimally invasive delivery route suitable for many applications. However, optimized thaw protocols that restore full biological potential of cryo-preserved MSC therapies prior to implantation must be developed. 相似文献2.
Pamela Sarkar Juliana Redondo Kevin Kemp Mark Ginty Alastair Wilkins Neil J. Scolding Claire M. Rice 《Cytotherapy》2018,20(1):21-28
Background
Clinical trials using ex vivo expansion of autologous mesenchymal stromal cells (MSCs) are in progress for several neurological diseases including multiple sclerosis (MS). Given that environment alters MSC function, we examined whether in vitro expansion, increasing donor age and progressive MS affect the neuroprotective properties of the MSC secretome.Methods
Comparative analyses of neuronal survival in the presence of MSC-conditioned medium (MSCcm) isolated from control subjects (C-MSCcm) and those with MS (MS-MSCcm) were performed following (1) trophic factor withdrawal and (2) nitric oxide–induced neurotoxicity.Results
Reduced neuronal survival following trophic factor withdrawal was seen in association with increasing expansion of MSCs in vitro and MSC donor age. Controlling for these factors, there was an independent, negative effect of progressive MS. In nitric oxide neurotoxicity, MSCcm-mediated neuroprotection was reduced when C-MSCcm was isolated from higher-passage MSCs and was negatively associated with increasing MSC passage number and donor age. Furthermore, the neuroprotective effect of MSCcm was lost when MSCs were isolated from patients with MS.Discussion
Our findings have significant implications for MSC-based therapy in neurodegenerative conditions, particularly for autologous MSC therapy in MS. Impaired neuroprotection mediated by the MSC secretome in progressive MS may reflect reduced reparative potential of autologous MSC-based therapy in MS and it is likely that the causes must be addressed before the full potential of MSC-based therapy is realized. Additionally, we anticipate that understanding the mechanisms responsible will contribute new insights into MS pathogenesis and may also be of wider relevance to other neurodegenerative conditions. 相似文献3.
Aim
Establishment of a potency assay in the manufacturing of clinical-grade mesenchymal stromal cells (MSCs) has been a challenge due to issues of relevance to function, timeline and variability of responder cells. In this study, we attempted to develop a potency assay for MSCs.Methods
Clinical-grade bone marrow–derived MSCs were manufactured. The phenotype and immunosuppressive functions of the MSCs were evaluated based on the International Society for Cellular Therapy guidelines. Resting MSCs licensed by interferon (IFN)-γ exposure overnight were evaluated for changes in immune suppression and immune-relevant proteins. The relationship of immune-relevant protein expression with immunosuppression of MSCs was analyzed.Results
MSC supressed third-party T-lymphocyte proliferation with high inter-donor and inter-test variability. The suppression of T-lymphocyte proliferation by IFN-γ–licensed MSCs correlated with that by resting MSCs. Many cellular proteins were up-regulated after IFN-γ exposure, including indoleamine 2,3-dioxygenase 1 (IDO-1), programmed death ligand 1 (PD-L1), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and bone marrow stromal antigen 2 (BST-2). The expression levels of IDO-1 and PD-L1 on licensed MSCs, not VCAM-1, ICAM-1 or BST-2 on licensed MSCs, correlated with MSC suppression of third-party T-cell proliferation.Conclusion
A flow cytometry–based assay of MSCs post–IFN-γ exposure measuring expression of intracellular protein IDO-1 and cell surface protein PD-L1 captures two mechanisms of suppression and offers the potential of a relevant, rapid assay for MSC-mediated immune suppression that would fit with the manufacturing process. 相似文献4.
Samantha F.H. De Witte Fleur S. Peters Ana Merino Sander S. Korevaar Joyce B.J. Van Meurs Lisa O&#x;Flynn Steve J. Elliman Philip N. Newsome Karin Boer Carla C. Baan Martin J. Hoogduijn 《Cytotherapy》2018,20(7):919-929
Background
Mesenchymal stromal cells (MSCs) are studied for their immunotherapeutic potential. Prior to therapeutic use, MSCs are culture expanded to obtain the required cell numbers and, to improve their efficacy, MSCs may be primed in vitro. Culture expansion and priming induce phenotypical and functional changes in MSCs and thus standardisation and quality control measurements come in need. We investigated the impact of priming and culturing on MSC DNA methylation and examined the use of epigenetic profiling as a quality control tool.Methods
Human umbilical cord–derived MSCs (ucMSCs) were cultured for 3 days with interferon (IFN)γ, transforming growth factor (TGF)β or a multi-factor combination (MC; IFNγ, TGFβ and retinoic acid). In addition, ucMSCs were culture expanded for 14 days. Phenotypical changes and T-cell proliferation inhibition capacity were examined. Genome-wide DNA methylation was measured with Infinium MethylationEPIC Beadchip.Results
Upon priming, ucMSCs exhibited a different immunophenotype and ucMSC(IFNγ) and ucMSC(MC) had an increased capacity to inhibit T-cell proliferation. DNA methylation patterns were minimally affected by priming, with only one significantly differentially methylated site (DMS) in IFNγ- and MC-primed ucMSCs associated with autophagy activity. In contrast, 14 days after culture expansion, ucMSCs displayed minor phenotypical and functional changes but showed >4000 significantly DMSs, mostly concerning genes involved in membrane composition, cell adhesion and transmembrane signalling.Discussion
These data show that DNA methylation of MSCs is only marginally affected by priming, whereas culture expansion and subsequent increased cellular interactions have a large impact on methylation. On account of this study, we suggest that DNA methylation analysis is a useful quality control tool for culture expanded therapeutic MSCs. 相似文献5.
Sara Savelli Luisa Trombi Delfo D&#x;Alessandro Stefania Moscato Simone Pacini Stefano Giannotti Simone Lapi Fabrizio Scatena Mario Petrini 《Cytotherapy》2018,20(4):556-563
Background
Bone Marrow MSCs are an appealing source for several cell-based therapies. Many bioreactors, as the Quantum Cell Expansion System, have been developed to generate a large number of MSCs under Good Manufacturing Practice conditions by using Human Platelet Lysate (HPL). Previously we isolated in the human bone marrow a novel cell population, named Mesodermal Progenitor Cells (MPCs), which we identified as precursors of MSCs. MPCs could represent an important cell source for regenerative medicine applications. As HPL gives rise to a homogeneus MSC population, limiting the harvesting of other cell types, in this study we investigated the efficacy of pooled human AB serum (ABS) to provide clinically relevant numbers of both MSCs and MPCs for regenerative medicine applications by using the Quantum System.Methods
Bone marrow aspirates were obtained from healthy adult individuals undergoing routine total hip replacement surgery and used to generate primary cultures in the bioreactor. HPL and ABS were tested as supplements to culture medium. Morphological observations, cytofluorimetric analysis, lactate and glucose level assessment were performed.Results
ABS gave rise to both heterogeneous MSC and MPC population. About 95% of cells cultured in HPL showed a fibroblast-like morphology and typical mesenchymal surface markers, but MPCs were scarcely represented.Discussion
The use of ABS appeared to sustain a large scale MSC production, as well as the recovery of a subset of MPCs, and resulted a suitable alternative to HPL in the cell generation based on the Quantum System. 相似文献6.
Atieh Makhlough Soroosh Shekarchian Reza Moghadasali Behzad Einollahi Mona Dastgheib Ghasem Janbabaee Seyedeh Esmat Hosseini Nasrin Falah Fateme Abbasi Hossein Baharvand Nasser Aghdami 《Cytotherapy》2018,20(5):660-669
Background
Chronic kidney disease (CKD) is a progressive loss of kidney function and structure that affects approximately 13% of the population worldwide. A recent meta-analysis revealed that cell-based therapies improve impaired renal function and structure in preclinical models of CKD. We assessed the safety and tolerability of bone marrow–mesenchymal stromal cell (MSC) infusion in patients with CKD.Methods
A single-arm study was carried out at one center with 18-month follow-up in seven eligible patients with CKD due to different etiologies such as hypertension, nephrotic syndrome (NS) and unknown etiology. We administered an intravenous infusion (1–2?×?106 cells/kg) of autologous cultured MSCs. The primary endpoint was safety, which was measured by number and severity of adverse events. The secondary endpoint was decrease in the rate of decrease in estimated glomerular filtration rate (eGFR). We compared kidney function during the follow-up visits to baseline and 18 months prior to the intervention.Results
Follow-up visits of all seven patients were completed; however, we have not observed any cell-related adverse events during the trial. Changes in eGFR (P?=?0.10) and serum creatinine (P?=?0.24) from 18 months before cell infusion to baseline in comparison with baseline to 18 months were not statistically significant.Conclusions
We showed safety and tolerability of a single-dose infusion of autologous MSCs in patients with CKD. 相似文献7.
Soraya Shadmanfar Narges Labibzadeh Mohsen Emadedin Neda Jaroughi Vajiheh Azimian Soura Mardpour Fatemeh Abbasi Kakroodi Tina Bolurieh Seyyedeh Esmat Hosseini Mohammad Chehrazi Maryam Niknejadi Hossein Baharvand Farhad Gharibdoost Nasser Aghdami 《Cytotherapy》2018,20(4):499-506
Background
In this study, we intend to assess the safety and tolerability of intra-articular knee implantation of autologous bone marrow–derived mesenchymal stromal cells (MSCs) in patients with rheumatoid arthritis (RA) and to determine the preliminary clinical efficacy data in this population. The trial registration numbers are as follows: Royan Institute Ethics Committee: AC/91/1133; NCT01873625.Methods
This single-center, randomized, triple-blind, placebo-controlled phase 1/2 clinical trial randomized RA patients with knee involvement to receive either an intra-articular knee implantation of 40 million autologous bone marrow–derived MSCs per joint or normal saline (placebo). Patients were followed up for 12 months to assess therapy outcomes.Results
A total of 30 patients, 15 in the MSC group and 15 in the placebo group, enrolled in this study. There were no adverse effects reported after MSC administration or during follow-up. Patients who received MSCs had superior findings according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), time to jelling and pain-free walking distance. However, this improvement could not be significantly sustained beyond 12 months. The MSC group exhibited improved standing time (P?=?0.01). In addition, the MSCs appeared to contribute to reductions in methotrexate and prednisolone use.Conclusion
Intra-articular knee implantation of MSCs appeared to be safe and well tolerated. In addition, we observed a trend toward clinical efficacy. These results, in our opinion, have justified the need for further investigations over an extended assessment period with larger numbers of RA patients who have knee involvement. 相似文献8.
Background
Cell therapy using mesenchymal stromal cells (MSCs) offers new perspectives in the treatment of traumatic brain injury (TBI). The aim of the present study was to assess the impact of platelet-rich plasma scaffolds (PRPS) as support of MSCs in a delayed phase after severe TBI in rats.Methods
TBI was produced by weight-drop impact to the right cerebral hemisphere. Two months after TBI, four experimental groups were established; saline, PRPS, MSCs in saline, or MSCs in PRPS was transplanted into the area of brain lesion through a small hole. All groups were evaluated in the course of the following 12 months after therapy and the animals were then humanely killed.Results
Our results showed that a greater functional improvement was obtained after the administration of MSCs in PRPS compared with the other experimental groups.Discussion
PRPS enhanced the benefit of cell therapy with MSCs to treat chronic brain damage in rats that suffered a severe TBI. The present findings suggest that the use of intralesional MSCs supported in PRPS may be a strategy of tissue engineering for patients with established neurological severe dysfunction after a TBI. 相似文献9.
Cagla Zubeyde Kopru Ilgin Cagnan Irem Akar Gunes Esendagli Petek Korkusuz Aysen Gunel-Ozcan 《Cytotherapy》2018,20(7):930-940
Background aims
TNFR family member glucocorticoid-induced tumor necrosis factor–related receptor (GITR/TNFRSF18) activation by its ligand glucocorticoid-induced TNF-related receptor ligand (GITRL) have important roles in proliferation, death and differentiation of cells. Some types of small cell lung cancers (SCLCs) express GITR. Because mesenchymal stromal cells (MSCs) may target tumor cells, we aimed to investigate the effect of MSCs carrying GITRL overexpressing plasmid on the proliferation and viability of a GITR+ SCLC cell line (SCLC-21H) compared with a GITR– SCLC cell line (NCI-H82).Methods
Electroporation was used to transfer pGITRL (GITRL gene carrying plasmid) or pCR3 (mock plasmid) into MSCs. Flow cytometry and semi-quantitative polymerase chain reaction were used to characterize the transfected MSCs. Following SCLC-21H or NCI-H82 cell lines were co-cultured with pGITRL-MSCs.Results
Proliferation of NCI-H82 was increased in all types of co-cultures while SCLC-21H cells did not. GITRL expressing MSCs were able to induce cell death of SCLC-21H through the upregulation of SIVA1 apoptosis inducing factor.Conclusions
The influence of MSCs on SCLC cells can vary according to the cancer cell subtypes as obtained in SCLC-21H and NCI-H82 and enabling GITR-GITRL interaction can induce cell death of SCLC cell lines. 相似文献10.
Lei Li Ryan Z.L. Lim Lawrence S.U. Lee Nicholas S.Y. Chew 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(8):1790-1800
Background
HIV infection and/or the direct pathogenic effects of circulating HIV proteins impairs the physiological function of mesenchymal stem cells (MSCs), and contribute to the pathogenesis of age-related clinical comorbidities in people living with HIV. The SDF-1/CXCR4 pathway is vital for modulating MSC proliferation, migration and differentiation. HIV glycoprotein gp120 inhibits SDF-1 induced chemotaxis by downregulating the expression and function of CXCR4 in monocytes, B and T cells. The influence of gp120 on CXCR4 expression and migration in MSCs is unknown.Methods
We investigated CXCR4 expression and SDF-1/CXCR4-mediated MSC migration in response to gp120, and its effect on downstream signaling pathways: focal adhesion kinase (FAK)/Paxillin and extracellular signal-regulated kinase (ERK).Results
Gp120 upregulated MSC CXCR4 expression. This potentiated the effects of SDF-1 in inducing chemotaxis; FAK/Paxillin and ERK pathways were over-activated, thereby facilitating actin stress fiber reorganization. CXCR4 blockage or depletion abrogated the observed effects.Conclusion
Gp120 from both T- and M- tropic HIV strains upregulated CXCR4 expression in MSCs, resulting in enhanced MSC chemotaxis in response to SDF-1.General significance
HIV infection and its proteins are known to disrupt physiological differentiation of MSC; increased gp120-driven migration amplifies the total MSC population destined for ineffective and inappropriate differentiation, thus contributing to the pathogenesis of HIV-related comorbidities. Additionally, given that MSCs are permissive to HIV infection, initial cellular priming by gp120 results in increased expression of CXCR4 and could lead to co-receptor switching and cell tropism changes in chronic HIV infection and may have implications against CCR5-knockout based HIV cure strategies. 相似文献11.
Background
Mesenchymal stromal cells (MSCs) can be used in several clinical applications. While MSCs are frequently cultured in fetal bovine serum for in vitro experimentation, human serum supplements are required for cells to be used in patients. Here we show how different human serum supplements and in vitro manipulations used during the cell culture impact on MSC proliferation rate and expression of inflammatory molecules.Methods
MSCs were cultured in medium supplemented with human plasma or serum combined with human platelet lysate (PL) and/or basic fibroblast growth factor (FGF2). Real time RT-PCR and western blot were used to assess expression of inflammatory cytokines.Results
Serum with addition of FGF2 gave the fastest proliferation rate. However, serum with FGF2 also increased expression of genes encoding inflammatory cytokines. The most favorable expansion condition for chondrogenic differentiation and inhibition of cartilage matrix degrading enzymes was plasma supplemented with PL and FGF2. Detachment of cells using trypsin gave considerable upregulation of inflammatory cytokine mRNAs which lasted for up to 24?h, with concomitant increase in protein levels. Even the gentle act of changing medium led to upregulation of cytokine mRNA, caused by addition of fresh serum.Discussion
Different culture conditions and simple cell manipulation influence proliferation rate and expression of inflammatory genes. Supplementing culture medium with allogeneic AB serum and FGF2 during monolayer expansion supported cell expansion better than other supplements, but also induced the highest levels of inflammatory cytokines and gave inferior results for chondrogenic differentiation. The importance of the composition of the culture medium and even gentle in vitro manipulation of the cells should be taken into account in the planning of procedures using in vitro expanded MSCs. 相似文献12.
Matthew L. Stone Yunge Zhao J. Robert Smith Mark L. Weiss Irving L. Kron Victor E. Laubach Ashish K. Sharma 《Respiratory research》2017,18(1):212
Background
Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs.Methods
C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs.Results
Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix.Conclusions
These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of donor lungs. The therapeutic benefits of EVs are in part mediated through anti-inflammatory promoting mechanisms via attenuation of immune cell activation as well as prevention of endothelial barrier integrity to prevent lung edema. Therefore, MSC-derived EVs offer a potential therapeutic strategy to treat post-transplant IR injury as well as rehabilitation of DCD lungs.13.
Takahiro Asami Makoto Ishii Ho Namkoong Kazuma Yagi Sadatomo Tasaka Takanori Asakura Shoji Suzuki Tetsuro Kamo Satoshi Okamori Hirofumi Kamata Haiyue Zhang Ahmed E. Hegab Naoki Hasegawa Tomoko Betsuyaku 《Cytotherapy》2018,20(3):302-313
Background
Pneumonia is the fourth leading cause of death worldwide, and Streptococcus pneumoniae is the most commonly associated pathogen. Increasing evidence suggests that mesenchymal stromal cells (MSCs) have anti-inflammatory roles during innate immune responses such as sepsis. However, little is known about the effect of MSCs on pneumococcal pneumonia.Methods
Bone marrow–derived macrophages (BMDMs) were stimulated with various ligands in the presence or absence of MSC-conditioned medium. For in vivo studies, mice intranasally-inoculated with S. pneumoniae were intravenously treated with MSCs or vehicle, and various parameters were assessed.Results
After stimulation with toll-like receptor (TLR) 2, TLR9 or TLR4 ligands, or live S. pneumoniae, TNF-α and interleukin (IL)–6 levels were significantly decreased, whereas IL-10 was significantly increased in BMDMs cultured in MSC-conditioned medium. In mice, MSC treatment decreased the number of neutrophils in bronchoalveolar lavage fluid (BALF) after pneumococcal infection, and this was associated with a decrease in myeloperoxidase activity in the lungs. Levels of proinflammatory cytokines, including TNF-α, IL-6, GM-CSF and IFN-γ, were significantly lower in MSC-treated mice, and the bacterial load in the lung after pneumococcal infection was significantly reduced. In addition, histopathologic analysis confirmed a decrease in the number of cells recruited to the lungs; however, lung edema, protein leakage into the BALF and levels of the antibacterial protein lipocalin 2 in the BALF were comparable between the groups.Conclusions
These results indicate that MSCs could represent a potential therapeutic application for the treatment of pneumonia caused by S. pneumoniae. 相似文献14.
Nadia Starc Min Li Mattia Algeri Antonella Conforti Luigi Tomao Angela Pitisci Francesco Emma Giovanni Montini Piergiorgio Messa Franco Locatelli Maria Ester Bernardo Marina Vivarelli 《Cytotherapy》2018,20(3):322-334
Background
Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases in the pediatric population; considering the role of the immune system in its pathogenesis, corticosteroids are used as first-line immunosuppressive treatment. Due to its chronic nature and tendency to relapse, a significant proportion of children experience co-morbidity due to prolonged exposure to corticosteroids and concomitant immunosuppression with second-line, steroid-sparing agents. Mesenchymal stromal cells (MSCs) are multipotent cells that represent a key component of the bone marrow (BM) microenvironment; given their unique immunoregulatory properties, their clinical use may be exploited as an alternative therapeutic approach in INS treatment.Methods
In view of the possibility of exploiting their immunoregulatory properties, we performed a phenotypical and functional characterization of MSCs isolated from BM of five INS patients (INS-MSCs; median age, 13 years; range, 11–16 years) in comparison with MSCs isolated from eight healthy donors (HD-MSCs). MSCs were expanded ex vivo and then analyzed for their properties.Results
Morphology, proliferative capacity, immunophenotype and differentiation potential did not differ between INS-MSCs and HD-MSCs. In an allogeneic setting, INS-MSCs were able to prevent both T- and B-cell proliferation and plasma-cell differentiation. In an in-vitro model of experimental damage to podocytes, co-culture with INS-MSCs appeared to be protective.Discussion
Our results demonstrate that INS-MSCs maintain the main biological and functional properties typical of HD-MSCs; these data suggest that MSCs may be used in autologous cellular therapy approaches for INS treatment. 相似文献15.
Jesús Vaquero Mercedes Zurita Miguel A. Rico Concepcion Aguayo Celia Bonilla Esperanza Marin Noemi Tapiador Marta Sevilla David Vazquez Joaquin Carballido Cecilia Fernandez Gregorio Rodriguez-Boto Mercedes Ovejero 《Cytotherapy》2018,20(6):806-819
Background aims
Cell therapy with autologous mesenchymal stromal cells (MSCs) in patients with spinal cord injury (SCI) is beginning, and the search for its better clinical application is an urgent need.Methods
We present a phase 2 clinical trial in patients with chronic SCI who received three intrathecal administrations of 100 x 106 MSCs and were followed for 10 months from the first administration. Efficacy analysis was performed on nine patients, and safety analysis was performed on 11 patients. Clinical scales, urodynamic, neurophysiological and neuroimaging studies were performed previous to treatment and at the end of the follow-up.Results
The treatment was well-tolerated, without any adverse event related to MSC administration. Patients showed variable clinical improvement in sensitivity, motor power, spasms, spasticity, neuropathic pain, sexual function or sphincter dysfunction, regardless of the level or degree of injury, age or time elapsed from the SCI. In the course of follow-up three patients, initially classified as ASIA A, B and C, changed to ASIA B, C and D, respectively. In urodynamic studies, at the end of follow-up, 66.6% of the patients showed decrease in postmicturition residue and improvement in bladder compliance. At this time, neurophysiological studies showed that 55.5% of patients improved in somatosensory or motor-evoked potentials, and that 44.4% of patients improved in voluntary muscle contraction together with infralesional active muscle reinnervation.Conclusions
The present guideline for cell therapy is safe and shows efficacy in patients with SCI, mainly in recovery of sphincter dysfunction, neuropathic pain and sensitivity. 相似文献16.
Background aims
Parotid hypofunction causes life-disrupting effects, and there are no effective medications for xerostomia. We hypothesized that mesenchymal stem cells (MSCs) have repairing effects on parotid glands of ovariectomized (OVX) rats.Methods
Forty-five adult female rats were divided into three equal groups: group I (Control group), group II (OVX-group) and group III (OVX rats that received MSCs at 4 and 8 weeks post-ovariectomy). At 12 weeks post-ovariectomy, histological (Masson's trichrome and periodic acid–Schiff with alcian blue stains), immunohistochemical (caspase-3 and CD44) and morphometric studies and salivary flow rate and saliva pH determination were carried out.Results
Histologically, the OVX group displayed numerous irregular vacuolated acini, thickened septa with marked cellular infiltration and vascular congestion. Degenerated organelles and few or irregular secretory granules with a different density were observed. Caspase-3-positive cells were highly expressed. MSC-treated glands exhibited a considerable degree of preservation of glandular architecture with numerous CD44-expressing and few caspase-3–expressing cells. Significant decrease of the salivary flow rate in the OVX group was detected, which reverted to normal levels in group III.Conclusions
MSCs ameliorated the damaging effects of ovariectomy on the parotid glands. 相似文献17.
18.
Ala Altaie Thomas G. Baboolal Owen Wall Elena Jones Dennis McGonagle 《Cytotherapy》2018,20(3):375-384
Background aims
Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid–derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury.Methods
SF-MSCs were obtained during knee arthroscopic procedures (N?=?7). Colony forming unit–fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions.Results
PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium.Conclusions
This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage. 相似文献19.
Background
Interleukin-35 (IL-35) has recently been identified as an immunosuppressive cytokine that has been used as a potential therapy for chronic inflammatory and autoimmune diseases. However, there remains a paucity of data regarding its potential benefits after integration into mesenchymal stem cells (MSCs).Methods
We used a dextran sulfate sodium (DSS)–induced colitis mice model and treated them with IL-35-MSCs, MSCs or saline. The body weight was recorded daily and inflammatory processes were determined. Cytokine secretion by lamina propria lymphocytes (LPLs) and percentage of regulatory T cells (Tregs) were also measured.Results
The data showed that mice in the two treated groups recovered their body weight more rapidly than mice treated with saline in the later stage of colitis. The colon lengths of IL-35-MSC–treated mice were markedly longer than those in the other two groups and the inflammation reduced significantly. Furthermore, the percentage of Foxp3?+?Tregs increased significantly and the level of proinflammatory cytokines produced by LPLs decreased significantly in the IL-35-MSC–treated group.Discussion
The results demonstrate that IL-35-MSCs could ameliorate ulcerative colitis by down-regulating the expression of pro-inflammatory cytokines. 相似文献20.
Simone Bettini Valeria Franceschini Laura Astolfi Edi Simoni Benedetta Mazzanti Alessandro Martini Roberto P. Revoltella 《Cytotherapy》2018,20(2):189-203