scholarly journals Magnetic Nanoparticle Based Nonviral MicroRNA Delivery into Freshly Isolated CD105+hMSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Anna Schade ◽  
Paula Müller ◽  
Evgenya Delyagina ◽  
Natalia Voronina ◽  
Anna Skorska ◽  
...  
Keyword(s):  
Stem Cell ◽  
Therapeutic Potential ◽  
Human Mesenchymal Stem Cells ◽  
Nucleic Acid Delivery ◽  
Innovative Strategies ◽  
Genetic Modifications ◽  
Microrna Delivery ◽  
Magnetic Vectors

Genetic modifications of bone marrow derived human mesenchymal stem cells (hMSCs) using microRNAs (miRs) may be used to improve their therapeutic potential and enable innovative strategies in tissue regeneration. However, most of the studies use cultured hMSCs, although these can lose their stem cell characteristics during expansion. Therefore, we aimed to develop a nonviral miR carrier based on polyethylenimine (PEI) bound to magnetic nanoparticles (MNPs) for efficient miR delivery in freshly isolated hMSCs. MNP based transfection is preferable for genetic modificationsin vivodue to improved selectivity, safety of delivery, and reduced side effects. Thus, in this study different miR/PEI and miR/PEI/MNP complex formulations were testedin vitrofor uptake efficiency and cytotoxicity with respect to the influence of an external magnetic field. Afterwards, optimized magnetic complexes were selected and compared to commercially available magnetic vectors (Magnetofectamine, CombiMag). We found that all tested transfection reagents had high miR uptake rates (yielded over 60%) and no significant cytotoxic effects. Our work may become crucial for virus-free introduction of therapeutic miRs as well as other nucleic acidsin vivo. Moreover, in the field of targeted stem cell therapy nucleic acid delivery prior to transplantation may allowfor initial cell modulationin vitro.

scholarly journals Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Bardelli ◽  
Marco Moccetti
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Translational Medicine ◽  
Process Development ◽  
Therapeutic Potential ◽  
Adult Stem Cell ◽  
Cell Renewal ◽  
Stem Cell Niches

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

scholarly journals Early Developmental Zebrafish Embryo Extract to Modulate Senescence in Multisource Human Mesenchymal Stem Cells

2019 ◽  
Vol 20 (11) ◽  
pp. 2646 ◽  
Author(s):  
Federica Facchin ◽  
Francesco Alviano ◽  
Silvia Canaider ◽  
Eva Bianconi ◽  
Martina Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Zebrafish Embryo ◽  
Human Mesenchymal Stem Cells ◽  
Cell Senescence ◽  
Embryo Extract ◽  
Early Developmental

Stem cells undergo senescence both in vivo, contributing to the progressive decline in self-healing mechanisms, and in vitro during prolonged expansion. Here, we show that an early developmental zebrafish embryo extract (ZF1) could act as a modulator of senescence in human mesenchymal stem cells (hMSCs) isolated from both adult tissues, including adipose tissue (hASCs), bone marrow (hBM-MSCs), dental pulp (hDP-MSCs), and a perinatal tissue such as the Wharton’s Jelly (hWJ-MSCs). In all the investigated hMSCs, ZF1 decreased senescence-associated β-galactosidase (SA β-gal) activity and enhanced the transcription of TERT, encoding the catalytic telomerase core. In addition, it was associated, only in hASCs, with a transcriptional induction of BMI1, a pleiotropic repressor of senescence. In hBM-MSCs, hDP-MSCs, and hWJ-MSCs, TERT over-expression was concomitant with a down-regulation of two repressors of TERT, TP53 (p53), and CDKN1A (p21). Furthermore, ZF1 increased the natural ability of hASCs to perform adipogenesis. These results indicate the chance of using ZF1 to modulate stem cell senescence in a source-related manner, to be potentially used as a tool to affect stem cell senescence in vitro. In addition, its anti-senescence action could also set the basis for future in vivo approaches promoting tissue rejuvenation bypassing stem cell transplantation.

scholarly journals Protect TUDCA stimulated CKD-derived hMSCs against the CKD-Ischemic disease via upregulation of PrPC

2018 ◽  
Author(s):  
Yeo Min Yoon ◽  
SangMin Kim ◽  
Yong-Seok Han ◽  
Chul Won Yun ◽  
Jun Hee Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
Blood Perfusion ◽  
Ischemic Disease ◽  
Tail Vein Injection ◽  
Promising Source ◽  
Dependent Pathway ◽  
Th 1

AbstractAlthough autologous human mesenchymal stem cells (hMSCs) are a promising source for regenerative stem cell therapy, the barriers associated with pathophysiological conditions in this disease limit therapeutic applicability to patients. We proved treatment of CKD-hMSCs with TUDCA enhanced the mitochondrial function of these cells and increased complex I & IV enzymatic activity, increasing PINK1 expression and decreasing mitochondrial O2•− and mitochondrial fusion in a PrPC-dependent pathway. Moreover, TH-1 cells enhanced viability when co-cultured in vitro with TUDCA-treated CKD-hMSC. In vivo, tail vein injection of TUDCA-treated CKD-hMSCs into the mouse model of CKD associated with hindlimb ischemia enhanced kidney recovery, the blood perfusion ratio, vessel formation, and prevented limb loss, and foot necrosis along with restored expression of PrPC in the blood serum of the mice. These data suggest that TUDCA-treated CKD-hMSCs are a promising new autologous stem cell therapeutic intervention that dually treats cardiovascular problems and CKD in patients.

Nanocarrier Mediated siRNA Delivery Targeting Stem Cell Differentiation

2020 ◽  
Vol 15 (2) ◽  
pp. 155-172 ◽  
Author(s):  
Fiona Fernandes ◽  
Pooja Kotharkar ◽  
Adrija Chakravorty ◽  
Meenal Kowshik ◽  
Indrani Talukdar
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Viral Vectors ◽  
Therapeutic Potential ◽  
Transfection Efficiency ◽  
Polymeric Nanoparticles ◽  
Sirna Delivery ◽  
Stem Cell Differentiation

Stem cell-based regenerative medicine holds exceptional therapeutic potential and hence the development of efficient techniques to enhance control over the rate of differentiation has been the focus of active research. One of the strategies to achieve this involves delivering siRNA into stem cells and exploiting the RNA interference (RNAi) mechanism. Transport of siRNA across the cell membrane is a challenge due to its anionic property, especially in primary human cells and stem cells. Moreover, naked siRNA incites immune responses, may cause off-target effects, exhibits low stability and is easily degraded by endonucleases in the bloodstream. Although siRNA delivery using viral vectors and electroporation has been used in stem cells, these methods demonstrate low transfection efficiency, cytotoxicity, immunogenicity, events of integration and may involve laborious customization. With the advent of nanotechnology, nanocarriers which act as novel gene delivery vehicles designed to overcome the problems associated with safety and practicality are being developed. The various nanomaterials that are currently being explored and discussed in this review include liposomes, carbon nanotubes, quantum dots, protein and peptide nanocarriers, magnetic nanoparticles, polymeric nanoparticles, etc. These nanodelivery agents exhibit advantages such as low immunogenic response, biocompatibility, design flexibility allowing for surface modification and functionalization, and control over the surface topography for achieving the desired rate of siRNA delivery and improved gene knockdown efficiency. This review also includes discussion on siRNA co-delivery with imaging agents, plasmid DNA, drugs etc. to achieve combined diagnostic and enhanced therapeutic functionality, both for in vitro and in vivo applications.

scholarly journals Human cardiac stem cells rejuvenated by modulating autophagy with MHY-1685 enhance the therapeutic potential for cardiac repair

2021 ◽  
Author(s):  
Ji Hye Park ◽  
Hyeok Kim ◽  
Hyung Ryong Moon ◽  
Bong-Woo Park ◽  
Jae-Hyun Park ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cardiac Fibrosis ◽  
Replicative Senescence ◽  
Therapeutic Potential ◽  
Mammalian Target Of Rapamycin ◽  
Cardiac Stem Cells ◽  
Differentiation Potential

AbstractStem cell-based therapies with clinical applications require millions of cells. Therefore, repeated subculture is essential for cellular expansion, which is often complicated by replicative senescence. Cellular senescence contributes to reduced stem cell regenerative potential as it inhibits stem cell proliferation and differentiation as well as the activation of the senescence-associated secretory phenotype (SASP). In this study, we employed MHY-1685, a novel mammalian target of rapamycin (mTOR) inhibitor, and examined its long-term priming effect on the activities of senile human cardiac stem cells (hCSCs) and the functional benefits of primed hCSCs after transplantation. In vitro experiments showed that the MHY-1685‒primed hCSCs exhibited higher viability in response to oxidative stress and an enhanced proliferation potential compared to that of the unprimed senile hCSCs. Interestingly, priming MHY-1685 enhanced the expression of stemness-related markers in senile hCSCs and provided the differentiation potential of hCSCs into vascular lineages. In vivo experiment with echocardiography showed that transplantation of MHY-1685‒primed hCSCs improved cardiac function than that of the unprimed senile hCSCs at 4 weeks post-MI. In addition, hearts transplanted with MHY-1685-primed hCSCs exhibited significantly lower cardiac fibrosis and higher capillary density than that of the unprimed senile hCSCs. In confocal fluorescence imaging, MHY-1685‒primed hCSCs survived for longer durations than that of the unprimed senile hCSCs and had a higher potential to differentiate into endothelial cells (ECs) within the infarcted hearts. These findings suggest that MHY-1685 can rejuvenate senile hCSCs by modulating autophagy and that as a senescence inhibitor, MHY-1685 can provide opportunities to improve hCSC-based myocardial regeneration.

scholarly journals Neural Stem Cell-Conditioned Medium Suppresses Inflammation and Promotes Spinal Cord Injury Recovery

2017 ◽  
Vol 26 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Zhijian Cheng ◽  
Dale B. Bosco ◽  
Li Sun ◽  
Xiaoming Chen ◽  
Yunsheng Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Conditioned Medium ◽  
Neural Stem Cell ◽  
Therapeutic Potential ◽  
Secondary Injury ◽  
Cord Injury

Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned medium (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors. Utilizing primary cell culture and murine models of SCI, we determined that systemic treatment with NSC-M was able to significantly improve motor function and lesion healing. In addition, NSC-M demonstrated significant anti-inflammatory potential in vitro and in vivo, reducing inflammatory cytokine expression in both activated macrophages and injured spinal cord tissues. NSC-M was also able to reduce the expression of inducible nitric oxide synthase (iNOS) within the spleen of injured animals, indicating an ability to reduce systemic inflammation. Thus, we believe that NSC-M offers a possible alternative to direct stem cell engraftment for the treatment of SCI.

scholarly journals A Chemically Defined Serum-Free Culture System for Spontaneous Human Mesenchymal Stem Cell Spheroid Formation

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Yajun Zhao ◽  
E. Xiao ◽  
Wanqi Lv ◽  
Xian Dong ◽  
Linhai He ◽  
...  
Keyword(s):  
Stem Cell ◽  
Culture System ◽  
Monolayer Culture ◽  
Therapeutic Potential ◽  
Spheroid Formation ◽  
Special Equipment ◽  
Spheroid Culture ◽  
Lps Challenge

Mesenchymal stem cells (MSCs) possess promising potential in tissue engineering and regenerative medicine. Previous studies demonstrated that spheroid formation of MSCs exhibited improved stemness maintenance and therapeutic potential compared with monolayer culture. To date, various spheroid culture systems have been developed but most of them required low adhesion conditions or special equipment. In this study, we demonstrated that inoculation of dissociated MSCs in TeSR-E8 medium could induce self-assemble spheroid formation in conventional tissue culture polystyrene dishes. Compared with monolayer culture, adipose-derived stem cell (ADSC) spheroids enhanced the proliferation and osteogenic capability of ADSCs compared with monolayer culture. When reseeded in normal serum-containing medium, the expression level of stemness biomarkers was even higher in spheroid-derived ADSCs than monolayer culture. Importantly, spheroid ADSCs could effectively promote the M2 polarization of macrophages both in vitro and in vivo. After transplantation into mouse, spheroid ADSCs improved the survival rate and significantly decreased serum levels of proinflammatory factors IL-1β and TNF-α following LPS challenge. In summary, we developed a 3D spheroid culture system through TeSR-E8 medium without the involvement of low adhesion conditions and special equipment, which provided a practical and convenient method for spheroid formation of MSCs with great potential for stem cell clinical therapy.

scholarly journals The therapeutic potential of stem cells

2010 ◽  
Vol 365 (1537) ◽  
pp. 155-163 ◽  
Author(s):  
Fiona M. Watt ◽  
Ryan R. Driskell
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Therapeutic Potential ◽  
Patient Specific ◽  
Religious Groups ◽  
Differentiation Potential ◽  
Cell Behaviour ◽  
Different Types

In recent years, there has been an explosion of interest in stem cells, not just within the scientific and medical communities but also among politicians, religious groups and ethicists. Here, we summarize the different types of stem cells that have been described: their origins in embryonic and adult tissues and their differentiation potential in vivo and in culture. We review some current clinical applications of stem cells, highlighting the problems encountered when going from proof-of-principle in the laboratory to widespread clinical practice. While some of the key genetic and epigenetic factors that determine stem cell properties have been identified, there is still much to be learned about how these factors interact. There is a growing realization of the importance of environmental factors in regulating stem cell behaviour and this is being explored by imaging stem cells in vivo and recreating artificial niches in vitro . New therapies, based on stem cell transplantation or endogenous stem cells, are emerging areas, as is drug discovery based on patient-specific pluripotent cells and cancer stem cells. What makes stem cell research so exciting is its tremendous potential to benefit human health and the opportunities for interdisciplinary research that it presents.

scholarly journals Investigation of the Therapeutic Potential of Momelotinib on Hepatitis Virus-Associated Liver Cancer Is Through Suppressing Oncogenic/Stemnes IFNGR-JAK-STAT Pathway

2020 ◽  
Author(s):  
Jiann Ruey Ong ◽  
Chi-Tai Yeh ◽  
Ting-Yi Huang ◽  
Ming-Shou Hsieh ◽  
Wei-Hwa Lee ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Cancer ◽  
Therapeutic Potential ◽  
Hepatitis Virus ◽  
Signal Transmission ◽  
Tumor Burden ◽  
Poor Overall Survival ◽  
Invasive Property

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, accounting for more than 700,000 deaths annually. In this study, we hypothesized that momelotinib could regulate the progression of HCC by targeting Jak family related protein. The proteins of IFN gamma-related pathways are obviously activated after hepatitis virus infection. This result suggests the difference in signal transmission between viral liver cancer and general liver cancer. Based on this observation, we are linked to the relevant targets of the JAK family and the potential applications of targeted therapy inhibitors.Methods: We analyzed possible synergism between Momelotinib and Sorafenib in hepatitis virus-associated liver cancer. Immunostaining, colony formation Assay, cell invasion, migration, and tumorsphere-formation assay was used drug cytotoxicity, cell viability and possible molecular mechanism. Result: We found that Jak2 downstream gene STAT1 expression was correlated with poor prognosis and poor overall survival of patients with HCC. Treatment of momelotinib significantly inhibits Jak2, resultant in the reduction of the migratory, invasive property of vHCC cells. Interestingly, cell cycle arrest and inhibition of the stem cell-like phenotype of vHCC cells were also observed after the momelotinib treatment. Furthermore, the combined effect of momelotinib and sorafenib both at in-vitro and in-vivo synergistically suppresses the proliferation of vHCC cells and effectively reduces the tumor burden.Conclusion: Our results showed that momelotinib effectively suppressed the expression of Jak2, which results in the downregulation of cancer stem cell genes and enhances the antitumor efficacy of sorafenib by initiating the expression of apoptosis-related genes in vHCC cells, thus maximizing its therapeutic potential for patients with HCC.

Immnuoregulatory Effect of Human Mesenchymal Stem Cell Is Mediated Via STAT3 Molecule

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4741-4741
Author(s):  
Jinsun Yoon ◽  
Seoju Kim ◽  
Eun Shil Kim ◽  
Byoungbae PARK ◽  
Junghye Choi ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Lymphocytes ◽  
Human Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cell ◽  
Treg Cells ◽  
Human Mscs ◽  
Hematopoietic Stem

Abstract The best curative treatment modality in hematologic malignancies is allogeneic hematopoietic stem cell transplantation (HSCT). Graft-versus-host disease (GVHD) is a major obstacle of allogenic HSCT. Bone marrow derived human mesenchymal stem cells (MSCs) is known to have immunoregulatory effect in vitro and in vivo via inhibiting alloreactive T lymphocytes, leading to their clinical use for the prevention of GVHD in HSCT. However, the molecular mechanism of immunoregulatory effect of human MSCs is not fully understood. In this study we investigated the signaling of immunoregulatory effect by co-culture of human MSCs with lymphocytes. The proliferation of allogeneic T cells was strongly inhibited. The fraction of CD4+CD25+Foxp3+ cells (Treg cells) was increased, while the fraction of CD4+, CD8+, CD25+ was decreased. In addition, induction of Th1 to Th2 shift was observed. Western blot study showed that phosphorylation of STAT1, STAT3, STAT6 was up-regulated, but STAT1, STAT4, ERK, AKT, NF-κB (p65, p50 subunits) was down-regulated. While expression of STAT3 was observed in culture of MSCs only, no expression of STAT3 was shown in co-cultured human MSCs with lymphocytes. In order to validate our results, expression of STAT3 in human MSCs co-cultured with lymphocytes was ablated using small interfering RNA. As a result, inhibition of CD4+CD25+FoxP3+ cells, proliferation of allogenic T lymphocytes, inhibited induction of Th1 to Th2 shift and proliferation of CD4+, CD8+, CD25+ cells. Furthermore, expressions of Th1 and Th17-related cytokines were increased, while expressions of Th2-related cytokines were decreased. In summary, these results suggest that STAT 3 may be an indispensable molecule in the immunoregulatory effects in human MSCs via modulation of regulatory T cells.

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