A low dose cell therapy system for treating osteoarthritis: In vivo study and in vitro mechanistic investigations

Intra-articular injection of mesenchymal stem cells (MSCs) in an osteoarthritic joint can help slow down cartilage destruction. However, cell survival and the efficiency of repair are generally low due to mechanical damage during injection and a high rate of cell loss. We, thus, investigated an improved strategy for cell delivery to an osteoarthritic joint through the use of three-dimensional (3D) microcryogels. MSCs were seeded into 3D microcryogels. The viability and proliferation of MSCs in microcryogels were determined over 5 d, and the phenotype of MSCs was confirmed through trilineage differentiation tests and flow cytometry. In Sprague Dawley rats with induced osteoarthritis (OA) of the knee joint, a single injection was made with the following groups: saline control, low-dose free MSCs (1 × 105 cells), high-dose free MSCs (1 × 106 cells), and microcryogels + MSCs (1 × 105 cells). Cartilage degeneration was evaluated by macroscopic examination, micro-computed tomographic analysis, and histology. MSCs grown in microcryogels exhibited optimal viability and proliferation at 3 d with stable maintenance of phenotype in vitro. Microcryogels seeded with MSCs were, therefore, primed for 3 d before being used for in vivo experiments. At 4 and 8 wk, the microcryogels + MSCs and high-dose free MSC groups had significantly higher International Cartilage Repair Society macroscopic scores, histological evidence of more proteoglycan deposition and less cartilage loss accompanied by a lower Mankin score, and minimal radiographic evidence of osteoarthritic changes in the joint compared to the other two groups. In conclusion, intra-articular injection of cell-laden 3D microcryogels containing a low dose of MSCs can achieve similar effects as a high dose of free MSCs for OA in a rat model. Primed MSCs in 3D microcryogels can be considered as an improved delivery strategy for cell therapy in treating OA that minimizes cell dose while retaining therapeutic efficacy.

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Oxidative stress as antifibrogenic stimulus? Low dose steady state H2O2 induces fibrolytic MMP–3 in vitro and in vivo

Zeitschrift für Gastroenterologie ◽

10.1055/s-0031-1295764 ◽

2012 ◽

Vol 50 (01) ◽

Author(s):

G Millonig ◽

S Ottinger ◽

HK Seitz ◽

S Mueller

Keyword(s):

Oxidative Stress ◽

Steady State ◽

Low Dose

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Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

Perspectives in Surgery ◽

10.33699/pis.2019.98.9.350-355 ◽

2019 ◽

Vol 98 (9) ◽

pp. 350-355

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cell Therapy ◽

Portal Vein ◽

Liver Parenchyma ◽

Miniature Pig ◽

Hepatic Diseases ◽

Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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Ciamexon in low-dose streptozotocin induced diabetes mellitus. In vivo and in vitro studies

Acta Endocrinologica ◽

10.1530/acta.0.111s120 ◽

1986 ◽

Vol 113 (1_Suppl) ◽

pp. S120-S121

Author(s):

TH. LINN ◽

H. GERMANN ◽

B. HERING ◽

R. BRETZEL ◽

K. FEDERLIN

Keyword(s):

Diabetes Mellitus ◽

Low Dose ◽

In Vitro Studies ◽

Streptozotocin Induced Diabetes

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Faculty Opinions recommendation of A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1120094.576229 ◽

2008 ◽

Author(s):

Richard Riedel

Keyword(s):

Growth Factor ◽

Heat Shock ◽

Heat Shock Protein ◽

Ewing Sarcoma ◽

Heat Shock Protein 90 ◽

Pivotal Role ◽

In Vivo Study ◽

Insulin Like Growth Factor

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Biological effect of Egyptian Propolis on BHK cell line and on dental pulp tissue (An In vitro And In vivo study)

Egyptian Dental Journal ◽

10.21608/edj.2018.76780 ◽

2018 ◽

Vol 64 (3) ◽

pp. 2161-2170

Author(s):

Marwa Moussa ◽

Marwa Temirek

Keyword(s):

Cell Line ◽

Dental Pulp ◽

Biological Effect ◽

In Vivo Study ◽

Pulp Tissue ◽

Dental Pulp Tissue

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Formulation and Evaluation of Atorvastatin Calcium-Poly-ε-Caprolactone Nanoparticles Loaded Ocular Inserts for Sustained Release and Antiinflammatory Efficacy

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200519133350 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1688-1698

Author(s):

Germeen N.S. Girgis

Keyword(s):

Sustained Release ◽

In Vitro Release ◽

Pluronic F127 ◽

In Vivo Study ◽

Average Weight ◽

Drug Release Profile ◽

Atorvastatin Calcium ◽

Anti Inflammatory

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.

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