scholarly journals Iron nanoparticle-labeled murine mesenchymal stromal cells in an osteoarthritic model persists and demonstrates anti-inflammatory mechanism of action

2019 ◽  
Author(s):  
Amanda M. Hamilton ◽  
Wing-Yee Cheung ◽  
Alejandro Gómez-Aristizábal ◽  
Sayaka Nakamura ◽  
Amélie Chaboureau ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Prussian Blue ◽  
Mechanism Of Action ◽  
Cartilage Damage ◽  
Joint Inflammation ◽  
Knee Joints ◽  
Iron Oxide Nanoparticle ◽  
Saline Control ◽  
Post Surgery

AbstractOsteoarthritis (OA) is characterized by cartilage degradation and chronic joint inflammation. Mesenchymal stem cells (MSCs) have shown promising results in OA, but their mechanism of action is not fully understood. We hypothesize that MSCs polarize macrophages, which are strongly associated with joint inflammation to more homeostatic sub-types. We tracked ferumoxytol (Feraheme™, iron oxide nanoparticle)-labeled murine MSCs (Fe-MSCs) in murine OA joints, and quantified changes to homeostatic macrophages.10-week-old C57BL/6 male mice (n=5/group) were induced to undergo osteoarthritis by destabilization of medical meniscus (DMM) or sham surgery. 3 weeks post-surgery, mice were injected intra-articularly with either fluorescent dye-(DiR) labeled or DiR+ferumoxytol-labeled (DiR+Fe) bone marrow mesenchymal stem cells (MSC, 50×103MSCs/mouse) or saline (control), to yield 4 groups (n=5 per group for each timepoint [1, 2 and 4weeks]): i) DMM+Saline; ii) DMM+DiR+Fe-MSC; iii) DMM+DiR MSC; iv) SHAM+DiR+Fe-MSC and saline in contralateral knee. 4 weeks after injection, mice were imaged by MRI, and scored for i) OARSI to determine cartilage damage and ii) immunohistochemical changes in CD206, F480 and Prussian Blue/Sca-1 to detect homeostatic macrophages, total macrophages and ferumoxytol-labeled MSCs respectively.Ferumoxytol-labeled MSCs persisted in DMM knee joints at greater levels than in SHAM-MSC knee joints. We observed no difference in OARSI scores between MSC and vehicle groups. Sca-1 and Prussian Blue co-staining confirmed the ferumoxytol label resides in MSCs, although some ferumoxytol label was detected in proximity to MSCs in macrophages, likely due to phagocytosis of apoptotic MSCs, increasing functionality of these macrophages through MSC efferocytosis. We showed decreased MRI synovitis scores in MSC-treated compared to control animals. For the first time we show that MSC-treated OA mice had increased macrophage infiltration (p<0.08) with an increased proportion of CD206+ (homeostatic) macrophages (p<0.01), supporting our hypothesis that MSCs modulate synovial inflammation.

scholarly journals Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kangkang Zha ◽  
Xu Li ◽  
Zhen Yang ◽  
Guangzhao Tian ◽  
Zhiqiang Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Damage ◽  
Cartilage Regeneration ◽  
Great Promise ◽  
Traditional Treatment ◽  
Different Types ◽  
Selection Of

AbstractArticular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.

scholarly journals Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Weiping Lin ◽  
Zhengmeng Yang ◽  
Liu Shi ◽  
Haixing Wang ◽  
Qi Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Subchondral Bone ◽  
Peripheral Blood ◽  
Cartilage Degradation ◽  
Cartilage Tissue ◽  
Synovial Joint ◽  
Post Surgery ◽  
Sham Surgery

Abstract Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

scholarly journals Mechanism of Action of Icariin in Bone Marrow Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Aofei Yang ◽  
Chaochao Yu ◽  
Qilin Lu ◽  
Hao Li ◽  
Zhanghua Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Mechanism Of Action ◽  
Underlying Mechanism ◽  
Bone Defects ◽  
Clinical Use ◽  
Regenerative Therapy ◽  
Herba Epimedii ◽  
Marrow Mesenchymal Stem Cells

Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.

Mesenchymal Stem Cells in Rat Hepatic Fibrosis MModel: Benefits? Mechanism of Action?: 2017 Presidential Poster Award

2017 ◽  
Vol 112 ◽  
pp. S521
Author(s):  
Deniz Guney Duman ◽  
Umit Mustafa Ugurlu ◽  
Noushin Zibandeh ◽  
Tolga Akkoc ◽  
Munkhtsetseg Banzragch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hepatic Fibrosis ◽  
Mechanism Of Action ◽  
Poster Award

174 Use of mesenchymal stem cell treatment to improve oocyte yield and invitro embryo production in cattle

2020 ◽  
Vol 32 (2) ◽  
pp. 214
Author(s):  
M. Peixer ◽  
P. Malard ◽  
J. Carvalho ◽  
M. Dode ◽  
J. Viana ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Repeated Measures ◽  
Treatment Time ◽  
Left Ovary ◽  
Saline Control ◽  
Embryo Production ◽  
Oocyte Yield ◽  
The Right ◽  
Phosphate Buffered Saline

Cumulative tissue damage and chronic inflammation associated with frequent ovum pickup (OPU) may lead to a progressive reduction in the number and quality of the oocytes recovered, particularly in donors with a high antral follicle count. The aim of this study was to evaluate the effect of an intraovarian treatment with mesenchymal stem cells (MSC) on oocyte yield, quality, and development potential during invitro embryo production (IVEP) in cattle donors undergoing repeated OPU. Mesenchymal stem cells were previously isolated from adipose tissue, cultured in Dulbecco's modified Eagle medium until reaching 80% confluence, isolated with trypsin, and frozen in liquid N2 until use. Characterisation of MSC was carried out according to the guidelines of the International Society for Cellular Therapy. Nelore (Bos indicus) cows (n=5) were used in this study, with the ovaries as replicates. The cows underwent eight OPU sessions at 15-day intervals, and the oocytes recovered were graded and used for IVEP with the semen of a single sire and batch under similar invitro culture conditions. To ensure a high inflammatory response, immediately after the fourth OPU session all ovaries received 30 additional punctures, performed with a 16-gauge Jelco needle. Six hours later, the left ovary of each cow was injected with 500µL of Dulbecco's modified phosphate buffered saline (control ovary) and the right ovary received 500µL of Dulbecco's modified phosphate buffered saline with 2.5×106 allogenic MSC (treated ovary). Oocyte yield and embryo production before and after treatment were recorded for each ovary and donor. Grade I blastocysts produced from control and treated ovaries were used for gene expression evaluation. Data was analysed using the repeated-measures procedure of SAS (SAS Institute Inc.) to account for the effects of treatment, time, and interactions. There was no difference (P&gt;0.05) in any endpoint before treatment (sessions 1-4) between the right and left ovaries. Thus, differences between ovaries observed in OPU sessions 5-8 were assumed to be due to the treatment. After the injection of MSC, more total and viable oocytes were collected from the right ovaries compared with the left ovaries (15.3±2.2 vs. 8.7±1.2 (P&lt;0.02) and 13.6±2.1 vs. 7.1±1.0 (P&lt;0.01), respectively), resulting in more embryos produced invitro (7.6±1.2 vs. 3.6±0.6, respectively; P&lt;0.01) as well as more initial and expanded blastocysts (1.4±0.3 vs. 0.4±0.1 and 4.4±0.9 vs. 2.1±0.4, respectively; P&lt;0.04). The proportion of viable oocytes recovered from the right ovary after treatment was greater than that from the left ovary (89.1% vs. 81.5%; P&lt;0.05). However, blastocyst rates did not differ between ovaries before or after treatment (50.4% vs. 55.5%: P&gt;0.05). In the blastocysts produced from treated ovaries, SLC2A3 was overexpressed (P&lt;0.04), whereas there was no difference for the expression of KRT8, PLAC8, SLC2A1, CASP3, PRDX3, or SOD2 (P&gt;0.05), suggesting potential differences in glucose uptake and metabolism. In conclusion, intraovarian treatment with MSC improved oocyte yield and quality and may be an alternative to increase IVEP from donors under intensive OPU schedules. This research was supported by CNPq, CAPES, and Fazenda Grupo Esplanada.

scholarly journals Therapeutic Effects of Transplantation of As-MiR-937-Expressing Mesenchymal Stem Cells in Murine Model of Alzheimer's Disease

2015 ◽  
Vol 37 (1) ◽  
pp. 321-330 ◽  
Author(s):  
Zhen Liu ◽  
Cunfu Wang ◽  
Xiao Wang ◽  
Shunliang Xu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Social Recognition ◽  
Saline Control ◽  
Mouse Bone Marrow ◽  
Therapeutic Effects ◽  
Mrna Levels

Background/Aims: Alzheimer's disease (AD) is one of the most common dementias among aged people, and is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits. So far, this is no cure for AD. A therapeutic effect of transplantation of mesenchymal stem cells (MSCs) into murine model of AD has been reported, but remains to be further improved. Brn-4 is a transcription factor that plays a critical role in neuronal development, whereas the effects of Brn-4 overexpression in transplanted MSCs on AD are unknown. Methods: MSCs were isolated from mouse bone marrow and induced to overexpress antisense of miRNA-937 (as-miR-937) through adeno-associated virus (AAV)-mediated transduction, and purified by flow cytometry based on expression of a GFP co-transgene in the cells. The Brn-4 levels in mouse MSCs were examined in miR-937-modified MSCs by RT-qPCR and by Western blot. These miR-937-modified MSCs were then transplanted into an APP/PS1 transgenic AD model in mice. The effects of saline control, MSCs and asmiR-937 MSCs on AD mice were examined by deposition of amyloid-beta peptide aggregates (Aβ), social recognition test (SR), Plus-Maze Discriminative Avoidance Task (PM-DAT) and the levels of Brain-derived neurotrophic factor (BDNF) in the mouse brain. Results: MSCs expressed high levels of Brn-4 transcripts but low levels of Brn-4 protein. Poor protein vs mRNA levels of Brn-4 in MSCs appeared to result from the presence of high levels of miR-937 in MSCs. miR-937 inhibited translation of Brn-4 mRNA through binding to the 3'-UTR of the Brn-4 mRNA in MSCs. Expression of as-miR-937 significantly increased Brn-4 protein levels in MSCs. Transplantation of as-miR-937-expressing MSCs significantly reduced the deposition of Aβ, increased the levels of BDNF, and significantly improved the appearance in SR and PM-DAT in AD mice. Conclusion: Overexpression of as-miR-937 in MSCs may substantially improve the therapeutic effects of MSCs on AD, possibly through augmenting Brn-4 levels in MSCs.

scholarly journals Preclinical Studies of the Biosafety and Efficacy of Human Bone Marrow Mesenchymal Stem Cells Pre-Seeded into β-TCP Scaffolds after Transplantation

Materials ◽  
2018 ◽  
Vol 11 (8) ◽  
pp. 1349 ◽  
Author(s):  
Mar Gonzálvez-García ◽  
Carlos Martinez ◽  
Victor Villanueva ◽  
Ana García-Hernández ◽  
Miguel Blanquer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Clinical Signs ◽  
Bone Diseases ◽  
Scid Mice ◽  
Human Bone ◽  
Saline Control ◽  
Subchronic Toxicity ◽  
Toxic Response

Background: Cell-Based Therapies (CBT) constitute a valid procedure for increasing the quantity and quality of bone in areas with an inadequate bone volume. However, safety and efficacy should be investigated prior to clinical application. The objective of this study was to evaluate the biodistribution, safety and osteogenic capacity of bone marrow-derived human mesenchymal stem cells (hBMMSCs) pre-seeded into β-tricalcium phosphate (TCP) and implanted into NOD/SCID mice at subcutaneous and intramuscular sites. Methods: hBMMSCs were isolated, characterized and then cultured in vitro on a porous β-TCP scaffold. Cell viability and attachment were analyzed and then hBMMSCs seeded constructs were surgically placed at subcutaneous and intramuscular dorsal sites into NOD/SCID mice. Acute and subchronic toxicity, cell biodistribution and efficacy were investigated. Results: There were no deaths or adverse events in treated mice during the 48-hour observation period, and no toxic response was observed in mice. In the 12-week subchronic toxicity study, no mortalities, abnormal behavioral symptoms or clinical signs were observed in the saline control mice or the hBMMSCs/β-TCP groups. Finally, our results showed the bone-forming capacity of hBMMSCs/β-TCP since immunohistochemical expression of human osteocalcin was detected from week 7. Conclusions: These results show that transplantation of hBMMSCs/β-TCP in NOD/SCID mice are safe and effective, and might be applied to human bone diseases in future clinical trials.

scholarly journals Intra-Articular Injection of Alginate-Microencapsulated Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Osteoarthritis in Rabbits

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Seongjae Choi ◽  
Jun-Hyung Kim ◽  
Jeongho Ha ◽  
Bo-Ing Jeong ◽  
Yun Chan Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Femoral Condyle ◽  
Cruciate Ligament ◽  
Cartilage Damage ◽  
Rabbit Model ◽  
Cartilage Degradation ◽  
Research Society ◽  
Femoral Condyles

We investigated the effects of intra-articular injections of alginate-microencapsulated adipose tissue-derived mesenchymal stem cells (ASCs) during osteoarthritis (OA) development in a rabbit model of anterior cruciate ligament transection (ACLT). We induced OA in mature New Zealand white rabbits by bilateral ACLT. Stifle joints were categorised into four groups according to intra-articular injection materials. Alginate microbeads and microencapsulated ASCs were prepared using the vibrational nozzle technology. Two weeks after ACLT, the rabbits received three consecutive weekly intra-articular injections of 0.9% NaCl, alginate microbeads, ASCs, or microencapsulated ASCs, into each joint. Nine weeks after ACLT, we euthanised the rabbits and collected bilateral femoral condyles for macroscopic, histological, and immunohistochemical analyses. Macroscopic evaluation using the modified OA Research Society International (OARSI) score and total cartilage damage score showed that cartilage degradation on the femoral condyle was relatively low in the microencapsulated-ASC group. Histological analysis of the lateral femoral condyles indicated that microencapsulated ASCs had significant chondroprotective effects. Immunohistochemically, the expression of MMP-13 after the articular cartilage damage was relatively low in the microencapsulated-ASC-treated stifle joints. During the development of experimental OA, as compared to ASCs alone, intra-articular injection of microencapsulated ASCs significantly decreased the progression and extent of OA.

Sign in / Sign up

Export Citation Format

Share Document