scholarly journals Insights into the Secretome of Mesenchymal Stem Cells and Its Potential Applications

2019 ◽  
Vol 20 (18) ◽  
pp. 4597 ◽  
Author(s):  
Sharon Eleuteri ◽  
Alessandra Fierabracci
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Therapeutic Response ◽  
Diagnostic Procedures ◽  
Clinical Applications ◽  
Potential Applications

Mesenchymal stem cells (MSCs) have regenerative, immunoregulatory properties and can be easily isolated and expanded in vitro. Despite being a powerful tool for clinical applications, they present limitations in terms of delivery, safety, and variability of therapeutic response. Interestingly, the MSC secretome composed by cytokines, chemokines, growth factors, proteins, and extracellular vesicles, could represent a valid alternative to their use. It is noteworthy that MSC-derived extracellular vesicles (MSC-EVs) have the same effect and could be advantageous compared to the parental cells because of their specific miRNAs load. MiRNAs could be useful both in diagnostic procedures such as “liquid biopsy” to identify early pathologies and in the therapeutic field. Not only are MSC-EVs’ preservation, transfer, and production easier, but their administration is also safer, hence some clinical trials are ongoing. However, much effort is required to improve the characterization of EVs to avoid artifacts and guarantee reproducibility of the studies.

scholarly journals Expanded mesenchymal stem cell transplantation is safe in both local injection and vein transfusion

2017 ◽  
Vol 4 (3-4) ◽  
pp. 234-235 ◽  
Author(s):  
Vlassov V Salval ◽  
Yone Moto
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Clinical Applications ◽  
Local Injection ◽  
Mesenchymal Stem Cell Transplantation ◽  
Routine Treatment ◽  
Drug Products ◽  
The World

More than 500 clinical trials are using mesenchymal stem cells (MSCs) in the world to treat some different diseases. The safety of expanded MSC transplantation is the most important thing to ensure that this therapy can become the routine treatment for human diseases. More than five MSCs based stem cell drug products are approved at various countries demonstrated that expanded MSCs are safe in both local injection and transfusion. Moreover, some recent reports for 5 and 10 years followed-up clinical trials using expanded MSCs confirmed that there is not different tumorigenesis between the patients with and without expanded MSC transplantation. This letter aims to provide some evidences about the safety of expanded MSCs in clinical applications. However, the MSC quality should be stritcly controlled during the in vitro MSC expansion.

scholarly journals Research Status of Mesenchymal Stem Cells in Liver Transplantation

2019 ◽  
Vol 28 (12) ◽  
pp. 1490-1506 ◽  
Author(s):  
Yu You ◽  
Di-guang Wen ◽  
Jian-ping Gong ◽  
Zuo-jin Liu
Keyword(s):  
Stem Cells ◽  
Liver Transplantation ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
In Vivo Studies ◽  
Cell Contact ◽  
Clinical Effects ◽  
Clinical Safety

Liver transplantation has been deemed the best choice for end-stage liver disease patients but immune rejection after surgery is still a serious problem. Patients have to take immunosuppressive drugs for a long time after liver transplantation, and this often leads to many side effects. Mesenchymal stem cells (MSCs) gradually became of interest to researchers because of their powerful immunomodulatory effects. In the past, a large number of in vitro and in vivo studies have demonstrated the great potential of MSCs for participation in posttransplant immunomodulation. In addition, MSCs also have properties that may potentially benefit patients undergoing liver transplantation. This article aims to provide an overview of the current understanding of the immunomodulation achieved by the application of MSCs in liver transplantation, to discuss the problems that may be encountered when using MSCs in clinical practice, and to describe some of the underlying capabilities of MSCs in liver transplantation. Cell–cell contact, soluble molecules, and exosomes have been suggested to be critical approaches to MSCs’ immunoregulation in vitro; however, the exact mechanism, especially in vivo, is still unclear. In recent years, the clinical safety of MSCs has been proven by a series of clinical trials. The obstacles to the clinical application of MSCs are decreasing, but large sample clinical trials involving MSCs are still needed to further study their clinical effects.

scholarly journals Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daphne Hingert ◽  
Karin Ekström ◽  
Jonathan Aldridge ◽  
Rosella Crescitelli ◽  
Helena Brisby
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Treatment Strategies ◽  
Human Mesenchymal Stem Cells ◽  
Invasive Treatment ◽  
Disc Cells ◽  
Apoptotic Activity

Abstract Background Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model. Methods hMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 × 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions. Results The findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs. Conclusion hMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.

scholarly journals Very Long-Chain C24:1 Ceramide Is Increased in Serum Extracellular Vesicles with Aging and Can Induce Senescence in Bone-Derived Mesenchymal Stem Cells

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 37 ◽  
Author(s):  
Andrew Khayrullin ◽  
Priyanka Krishnan ◽  
Luis Martinez-Nater ◽  
Bharati Mendhe ◽  
Sadanand Fulzele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Cardiovascular Health ◽  
Rhesus Macaques ◽  
Cell Communication ◽  
Size Exclusion ◽  
Target Cells ◽  
Serum Samples

Extracellular vesicles (EVs), including exosomes and microvesicles, function in cell-to-cell communication through delivery of proteins, lipids and microRNAs to target cells via endocytosis and membrane fusion. These vesicles are enriched in ceramide, a sphingolipid associated with the promotion of cell senescence and apoptosis. We investigated the ceramide profile of serum exosomes from young (24–40 yrs.) and older (75–90 yrs.) women and young (6–10 yrs.) and older (25–30 yrs.) rhesus macaques to define the role of circulating ceramides in the aging process. EVs were isolated using size-exclusion chromatography. Proteomic analysis was used to validate known exosome markers from Exocarta and nanoparticle tracking analysis used to characterize particle size and concentration. Specific ceramide species were identified with lipidomic analysis. Results show a significant increase in the average amount of C24:1 ceramide in EVs from older women (15.4 pmol/sample) compared to those from younger women (3.8 pmol/sample). Results were similar in non-human primate serum samples with increased amounts of C24:1 ceramide (9.3 pmol/sample) in older monkeys compared to the younger monkeys (1.8 pmol/sample). In vitro studies showed that primary bone-derived mesenchymal stem cells (BMSCs) readily endocytose serum EVs, and serum EVs loaded with C24:1 ceramide can induce BMSC senescence. Elevated ceramide levels have been associated with poor cardiovascular health and memory impairment in older adults. Our data suggest that circulating EVs carrying C24:1 ceramide may contribute directly to cell non-autonomous aging.

300 ESTABLISHMENT AND CHARACTERIZATION OF RAT MESENCHYMAL STEM CELLS

2011 ◽  
Vol 23 (1) ◽  
pp. 247
Author(s):  
T. H. Kim ◽  
B. G. Jeon ◽  
S. L. Lee ◽  
G. J. Rho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Transcriptional Factors ◽  
Skin Tissue ◽  
Rt Pcr ◽  
Alternative Source ◽  
Differentiated Cells ◽  
Fetal Bovine

Mesenchymal stem cells (MSC) are regarded as an attractive source for tissue engineering and regeneration, and bone marrow extract has been commonly used as a source of pluripotent MSC. However, skin tissue has recently been identified as a convenient alternative source of MSC. The present study was focused on the effect of characterised MSC derived from rat on expression of early transcriptional factors, alkaline phosphate (AP) activity, and in vitro differentiation into selected cell lineages. The MSC were isolated from 8-week-old s.d. rat’s ear skin and cultured in advanced DMEM supplemented with 10% fetal bovine serum at 37°C in a humidified atmosphere of 5% CO2 in air. To evaluate AP activity, cells were fixed with 3.7% formaldehyde solution and stained with Western Blue® (Promega, Madison, WI, USA). Expressions of early transcriptional factors (Oct-4, Sox2, and Nanog) were evaluated by RT-PCR. Differentiation into distinct mesenchymal lineages such as adipogenic, osteogenic, and neuron was done by following previously described protocols and assessed by lineage-specific stains. The specific genes in the osteocytes (osteocalcin, osteonectin, osteopontin, and Runx2), adipocytes (pparγ2, adiponectin, and aP2) or neuron (nestin, neurogenin 1, β-tublin, and nerve growth factor) were characterised by RT-PCR. The MSC were positive for AP activity and expressed Oct-4, Sox2, and Nanog. Following induction, MSC were successfully differentiated into adipocytes, osteocytes, and neurons. As adipocytes markers, aP2, pparγ2, and adiponectin were strongly detected in the adipocyte induced cells. Osteonectin, osteocalcin, Runx2, and osteopontin were expressed in the adipocyte induced cells. Futhermore, neuron-specific markers were clearly expressed in the neuronal differentiated cells. In conclusion, MSC have the capability of differentiation into multilineages including adipocytes, osteocytes, and neurons under the specific induction conditions. Skin tissue in rat can serve as an easily accessible and expandable alternative source for MSC harvesting and preclinical applications using an animal model. This work was supported by Grant No. 2007031034040 from Bio-organ and 200908FHT010204005 from Biogreen21, Republic of Korea.

191 Canine Mesenchymal Stem Cells as Therapeutic Agents in Spinal Cord Injured Dog

2018 ◽  
Vol 30 (1) ◽  
pp. 236 ◽  
Author(s):  
Y.-H. Choe ◽  
H.-J. Lee ◽  
S.-L. Lee ◽  
J.-H. Lee ◽  
B.-W. Park ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Agents ◽  
Clinical Applications ◽  
Pain Sensation ◽  
Differentiation Potential ◽  
Na Currents ◽  
Spinal Cord Injured

In the recent era of veterinary research, stem cells have gained special attention due to their efficiency and use in clinical applications. Mesenchymal stem cells (MSC) have been extensively studied over decades, and their prospect for clinical application is recognised in human medicine. Despite numerous reports in veterinary clinical trials of stem cells, few studies have been presented regarding the in vitro characterisation of canine mesenchymal stem cells (cMSC). Therefore, their efficacy as therapeutic agents in vitro has not been much elucidated. Canine adipose-derived mesenchymal stem cells (cAMSC) were characterised as per International Society for Cellular Therapy guidelines. Culturing cells showed spindle-like morphology and high proliferation rate. They displayed positive expression of mesenchymal markers CD44, CD90, and CD105, and lacked expression of CD34 and CD45. They were also positive for expression of pluripotency-related transcription factors (Oct3/4, Nanog, and Sox2) and showed differentiation potential towards mesodermal lineages. The cAMSC were further analysed for the neuronal trans-differentiation potential. Under appropriate differentiation conditions, cAMSC displayed distinctive dendritic morphology along with axon projections. Neuronal specific genes including Nestin, β-tubulin, neurofilament protein (NF-M, NF-H), and nerve growth factor (NGF) were also positively expressed. Nevertheless, functional analysis of neuronal differentiated cAMSC displayed voltage dependence and kinetics for transient K+ and Na+ currents (Ito). Both K+ and Na+ currents were recorded in differentiated MSC by voltage steps (between −120 and +60 mV for K+ currents, −40 and +50 mV for Na+ currents), whereas control undifferentiated MSC lacked the currents. Taken together, we concluded that the cAMSC have potential to differentiate into neuron-like cells. Based on these findings, we transplanted cAMSC into the spinal cord injured dogs to evaluate their clinical efficiency under approved medical guidelines set by Gyeongsang National University Animal Medical Center (Korea). Neurological examination showed that the injured dog had undergone hind limb paralysis and lost deep pain sensation due to an L2 spinal cord lesion, as detected by CT and MRI. The dog was diagnosed with traumatic L2 intradural spinal cord contusion, and decompression surgery was performed, but deep pain sensation did not recover. Therefore, each cAMSC (diluted in 0.5 mL of saline) was transplanted into spinal cord segment (L2~L3) 5 times at 1-week intervals. The dog showed mild recovery of deep pain sensation by neurological examinations and exhibited gradual improvement in hind limb function. Finally, we concluded that transplantation of cAMSC has a beneficial therapeutic effect on spinal cord injury. This study also provides a significant advantage in understanding the potential of MSC-based products in veterinary clinical applications.

scholarly journals A Simplified Method for the Aspiration of Bone Marrow from Patients Undergoing Hip and Knee Joint Replacement for Isolating Mesenchymal Stem Cells and In Vitro Chondrogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Subhash C. Juneja ◽  
Sowmya Viswanathan ◽  
Milan Ganguly ◽  
Christian Veillette
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Isolation And Characterization ◽  
Standard Operating ◽  
Total Knee ◽  
Detailed Protocol

The procedure for aspiration of bone marrow from the femur of patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA) may vary from an OR (operating room) to OR based on the surgeon’s skill and may lead to varied extent of clotting of the marrow and this, in turn, presents difficulty in the isolation of mesenchymal stem cells (MSCs) from such clotted bone marrow. We present a simple detailed protocol for aspirating bone marrow from such patients, isolation, and characterization of MSCs from the aspirated bone marrow specimens and show that the bone marrow presented no clotting or exhibited minimal clotting. This represents an economical source and convenient source of MSCs from bone marrow for use in regenerative medicine. Also, we presented the detailed protocol and showed that the MSCs derived from such bone marrow specimens exhibited MSCs characteristics and generated micromass cartilages, the recipe for regenerative medicine for osteoarthritis. The protocols we presented can be used as standard operating procedures (SOPs) by researchers and clinicians.

Isolation and Characterization of Mesenchymal Stem Cells from Chicken Liver

2020 ◽  
Vol 10 (1) ◽  
pp. 8-16
Author(s):  
Xibin Liu ◽  
Shuang Zhang ◽  
Weijun Guan ◽  
Dong Zheng
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Protein Markers ◽  
Multilineage Differentiation ◽  
Rt Pcr ◽  
Multipotent Stem Cells ◽  
Isolation And Characterization ◽  
Potential Applications ◽  
Polymerase Chain

Hepatic mesenchymal stem cells (HMSCs) are multipotent stem cells that is a vital part of the regeneration of hepatocytes after injury. In this study, HMSCs were isolated in embryonic livers from of 12-day-old chick embryo using collagenase, and the primary HMSCs were sub-cultured to passage. The protein markers of HMSCs, namely CD71, CD29 and CD44, were tested with immunofluorescence and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The proliferation of HMSCs in different passages was detected using growth curve, which shown a typically sigmoidal. And then, the pluripotent of HMSCs was analyzed, the results showed that HMSCs could directly induce to differentiate into neural-like cells, adipocytes, and osteoblasts. Our data illustrated that the chick HMSCs have same characteristics to those obtained from other species. The capacity of these cells for multilineage differentiation shows promise for many potential applications.

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