scholarly journals Mechanisms of unprimed and dexamethasone‐primed nonviral gene delivery to human mesenchymal stem cells

2018 ◽  
Vol 116 (2) ◽  
pp. 427-443 ◽  
Author(s):  
Andrew Hamann ◽  
Kelly Broad ◽  
Albert Nguyen ◽  
Angela K. Pannier
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Human Mesenchymal Stem Cells ◽  
Nonviral Gene Delivery

scholarly journals Enhanced PRL-1 expression in placenta-derived mesenchymal stem cells accelerates hepatic function via mitochondrial dynamics in a cirrhotic rat model

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jae Yeon Kim ◽  
Jong Ho Choi ◽  
Ji Hye Jun ◽  
Sohae Park ◽  
Jieun Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Cell Therapy ◽  
Delivery Systems ◽  
Nonviral Gene Delivery ◽  
Early Gene ◽  
Next Generation ◽  
Atp Production ◽  
Mitochondrial Functions

Abstract Background Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as an alternative cell therapy agent that has become a next-generation stem cell treatment. Phosphatase of regenerating liver-1 (PRL-1), an immediate early gene, plays a critical role during liver regeneration. Here, we generated enhanced PRL-1 in PD-MSCs (PD-MSCsPRL-1, PRL-1+) using lentiviral and nonviral gene delivery systems and investigated mitochondrial functions by PD-MSCPRL-1 transplantation for hepatic functions in a rat bile duct ligation (BDL) model. Methods PD-MSCsPRL-1 were generated by lentiviral and nonviral AMAXA gene delivery systems and analyzed for their characteristics and mitochondrial metabolic functions. Liver cirrhosis was induced in Sprague-Dawley (SD) rats using common BDL for 10 days. PKH67+ naïve and PD-MSCsPRL-1 using a nonviral sysyem (2 × 106 cells/animal) were intravenously administered into cirrhotic rats. The animals were sacrificed at 1, 2, 3, and 5 weeks after transplantation and engraftment of stem cells, and histopathological analysis and hepatic mitochondrial functions were performed. Results PD-MSCsPRL-1 were successfully generated using lentiviral and nonviral AMAXA systems and maintained characteristics similar to those of naïve cells. Compared with naïve cells, PD-MSCsPRL-1 improved respirational metabolic states of mitochondria. In particular, mitochondria in PD-MSCsPRL-1 generated by the nonviral AMAXA system showed a significant increase in the respirational metabolic state, including ATP production and mitochondrial biogenesis (*p < 0.05). Furthermore, transplantation of PD-MSCsPRL-1 using a nonviral AMAXA system promoted engraftment into injured target liver tissues of a rat BDL cirrhotic model and enhanced the metabolism of mitochondria via increased mtDNA and ATP production, thereby improving therapeutic efficacy. Conclusions Our findings will further our understanding of the therapeutic mechanism of enhanced MSCs and provide useful data for the development of next-generation MSC-based cell therapy and therapeutic strategies for regenerative medicine in liver disease.

scholarly journals Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Christian Bucher ◽  
Amiq Gazdhar ◽  
Lorin M. Benneker ◽  
Thomas Geiser ◽  
Benjamin Gantenbein-Ritter
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Transfer ◽  
Gene Delivery ◽  
Intervertebral Disc ◽  
Organ Culture ◽  
Nonviral Gene Delivery ◽  
Human Mscs ◽  
Differentiation Factor ◽  
Gdf5 Gene

Intervertebral disc (IVD) cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC) is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5) by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved byin vitroelectroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

scholarly journals Nonviral Gene Delivery to Mesenchymal Stem Cells Using Cationic Liposomes for Gene and Cell Therapy

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
C. Madeira ◽  
R. D. Mendes ◽  
S. C. Ribeiro ◽  
J. S. Boura ◽  
M. R. Aires-Barros ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Cationic Liposome ◽  
Nonviral Gene Delivery ◽  
Great Promise ◽  
Full Potential ◽  
Genetically Engineer ◽  
Or Gene ◽  
First Time

Mesenchymal stem cells (MSCs) hold a great promise for application in several therapies due to their unique biological characteristics. In order to harness their full potential in cell-or gene-based therapies it might be advantageous to enhance some of their features through gene delivery strategies. Accordingly, we are interested in developing an efficient and safe methodology to genetically engineer human bone marrow MSC (BM MSC), enhancing their therapeutic efficacy in Regenerative Medicine. The plasmid DNA delivery was optimized using a cationic liposome-based reagent. Transfection efficiencies ranged from ~2% to ~35%, resulting from using a Lipid/DNA ratio of 1.25 with a transgene expression of 7 days. Importantly, the number of plasmid copies in different cell passages was quantified for the first time and ~20,000 plasmid copies/cell were obtained independently of cell passage. As transfected MSC have shown high viabilities (>90%) and recoveries (>52%) while maintaining their multipotency, this might be an advantageous transfection strategy when the goal is to express a therapeutic gene in a safe and transient way.

PEO–PPO–PEO micelles as effective rAAV-mediated gene delivery systems to target human mesenchymal stem cells without altering their differentiation potency

2015 ◽  
Vol 27 ◽  
pp. 42-52 ◽  
Author(s):  
Ana Rey-Rico ◽  
Jagadeesh K. Venkatesan ◽  
Janina Frisch ◽  
Isabel Rial-Hermida ◽  
Gertrud Schmitt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Human Mesenchymal Stem Cells ◽  
Delivery Systems

scholarly journals Niosomes-based gene delivery systems for effective transfection of human mesenchymal stem cells

2021 ◽  
pp. 112307
Author(s):  
Natalia Carballo-Pedrares ◽  
Axel Kattar ◽  
Angel Concheiro ◽  
Carmen Alvarez-Lorenzo ◽  
Ana Rey-Rico
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Gene Delivery ◽  
Human Mesenchymal Stem Cells ◽  
Delivery Systems

scholarly journals Enhanced Transfection of Human Mesenchymal Stem Cells Using a Hyaluronic Acid/Calcium Phosphate Hybrid Gene Delivery System

Polymers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 798 ◽  
Author(s):  
Jung Eun Lee ◽  
Yue Yin ◽  
Su Yeon Lim ◽  
E. Seul Kim ◽  
Jaeback Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Calcium Phosphate ◽  
Gene Delivery ◽  
Delivery System ◽  
Gene Transfection ◽  
Human Mesenchymal Stem Cells ◽  
Bone Morphogenetic Protein 2 ◽  
Gene Delivery System

Human mesenchymal stem cells (hMSCs) show enormous potential in regenerative medicine and tissue engineering. However, current use of hMSCs in clinics is still limited because there is no appropriate way to control their behavior in vivo, such as differentiation to a desired cell type. Genetic modification may provide an opportunity to control the cells in an active manner. One of the major hurdles for genetic manipulation of hMSCs is the lack of an efficient and safe gene delivery system. Herein, biocompatible calcium phosphate (CaP)-based nanoparticles stabilized with a catechol-derivatized hyaluronic acid (dopa-HA) conjugate were used as a carrier for gene transfection to hMSCs for improved differentiation. Owing to the specific interactions between HA and CD44 of bone marrow-derived hMSCs, dopa-HA/CaP showed significantly higher transfection in hMSCs than branched polyethylenimine (bPEI, MW 25 kDa) with no cytotoxicity. The co-delivery of a plasmid DNA encoding bone morphogenetic protein 2 (BMP-2 pDNA) and micro RNA 148b (miRNA-148b) by dopa-HA/CaP achieved significantly improved osteogenic differentiation of hMSCs.

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