The Behavior of Human Mesenchymal Stem Cells in 3D Fibrin Clots: Dependence on Fibrinogen Concentration and Clot Structure

Ho, Wendy; Tawil, Bill; Dunn, James C.Y.; Wu, Benjamin M.

doi:10.1089/ten.2006.12.1587

Cited by 211 publications

(181 citation statements)

References 36 publications

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“…Thrombin buffer solution, on the other hand, contains calcium and sodium chlorides. High fibrinogen, and to a lesser extent low thrombin, concentrations have been shown to reduce the proliferation of human MSCs [7][8][9] and dermal fibroblasts [3]. The fibrinogen concentration thresholds determined by these studies, however, varied from 18 to 50 mg/mL fibrinogen.…”

Section: Introductionmentioning

confidence: 83%

“…More recently, they also have been proposed as scaffolding for cell delivery in several tissue engineering applications [2]. Numerous in vitro studies, indeed, have demonstrated the ability of fibrin gels to support survival, proliferation, and/or differentiation of many cell types [3][4][5][6], including mesenchymal stromal cells (MSCs) [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Influencing biophysical properties of fibrin with buffer solutions

et al. 2010

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Fibrin has been proposed as cell scaffold for numerous tissue engineering applications. While most of the studies have focused on fibrinogen and thrombin, other components of fibrin can also affect its properties. The present study aimed to evaluate the effects of buffer solution composition on fibrin biophysical properties. Fibrin scaffolds were synthesized with different calcium, chloride, and factor XIII (FXIII) final concentrations. Light transmission was determined as a relative, semi-quantitative estimator of fiber structure differences, and two compositions, resulting in translucent and opaque gels, were tested for mechanical and biological properties. Gels were seeded with mouse mesenchymal cells, C3H10T1/2, or bovine bone marrow-derived mesenchymal stromal cells and cultured up to 10 or 24 days, before cell number, morphology and distribution were evaluated. Calcium increased gel opacity (i.e., fiber thickness), while chloride and FXIII decreased it. Opaque gels displayed a fluid-like viscous behavior while translucent gels showed improved elastic properties. Both compositions supported survival of both cell types with opaque gels leading to better proliferation, but significant scaffold shrinkage after 17 days of culture. These results demonstrated that calcium, chloride, and FXIII modulate the biophysical properties of fibrin, and can be used to adjust mechanical and biological properties for tissue engineering applications.

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Section: Introductionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Influencing biophysical properties of fibrin with buffer solutions

et al. 2010

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“…The fibrinogen/thrombin concentration in the FG preparation has been shown to affect the structural properties of the scaffold, and in turn influence the proliferation rate and morphology of hMSCs. 27 Therefore, alterations in FG scaffold microstructure can influence its function as a delivery scaffold for AAV2. The aim of the current study was to assess, in vitro, the structural characteristics of FG hydrogels containing varying fibrinogen concentrations, their AAV2-particles release kinetics, and subsequent transgene expression in target cells for articular cartilage tissue engineering.…”

Section: Discussionmentioning

confidence: 99%

“…All of these advantages make FG an appealing scaffold for preclinical translational cartilage tissue engineering applications. It has been shown that diluted FG produces a more open fibrin network compared with undiluted FG scaffolds, 27 and that FG can act as an efficient scaffold for gene delivery. [28][29][30] In the current study, we investigated the effect of different fibrinogen dilutions during the preparation of FG scaffold on the delivery of AAV2 and their early effects on human BM-MSC (hBM-MSC) chondrogenesis in vitro.…”

Section: Introductionmentioning

confidence: 99%

Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Lee

Haleem

Yao

et al. 2011

Tissue Engineering Part A

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Fibrin glue (FG) is used in a variety of clinical applications and in the laboratory for localized and sustained release of factors potentially important for tissue engineering. However, the effect of different fibrinogen concentrations on FG scaffold delivery of bioactive adeno-associated viruses (AAVs) has not been established. This study was performed to test the hypothesis that FG concentration alters AAV release profiles, which affect AAV bioavailability. Gene transfer efficiency of AAV-GFP released from FG was measured using HEK-293 cells. Bioactivity of AAV transforming growth factor-beta1 (TGF-b 1 ) released from FG was assessed using the mink lung cell assay, and by measuring induction of cartilage-specific gene expression in human mesenchymal stem cells (hMSCs). Nondiluted FG had longer clotting times, smaller pore sizes, thicker fibers, and slower dissolution rate, resulting in reduced release of AAV. AAV release and gene transfer efficiency was higher with 25% and 50% FG than with the 75% and 100% FG. AAV-TGF-b 1 released from dilute-FG transduced hMSCs, resulting in higher concentrations of bioactive TGF-b 1 and greater upregulation of cartilage-specific gene expression compared with hMSC from undiluted FG. This study, showing improved release, transduction efficiency, and chondrogenic effect on hMSC of bioactive AAV-TGF-b 1 released from diluted FG, provides information important to optimization of this clinically available scaffold for therapeutic gene delivery, both in cartilage regeneration and for other tissue engineering applications.

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“…However, the commercially available product, unlike that used in this study, is not suitable for tissue engineering applications as the high crosslinking density of the fibrin network prevents cell migration within the construct [39,40]. Moreover, the PRP gel used in our current study can be an autologous preparation, which can be obtained easily in large quantities, at no extra cost [26] .…”

Section: Page 18 Of 35mentioning

confidence: 99%

Engineering New Bone via a Minimally Invasive Route Using Human Bone Marrow-Derived Stromal Cell Aggregates, Microceramic Particles, and Human Platelet-Rich Plasma Gel

Chatterjea

Yuan

Chatterjea

et al. 2013

Tissue Engineering Part A

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Tissue Engineering Part A eering new bone via a minimally invasive route using human bone marrow derived stromal cell aggregates, micro ceramic particles and human platelet rich plasma gel (doi: 10.1089(doi: 10. /ten.TEA.2012 This article has been peer-reviewed and accepted for publication, but has yet to undergo copyediting and proof correction. The final published version may differ from this proof. 2 AbstractThere is a rise in the popularity of arthroscopic procedures in orthopedics. However, the majority of cell based bone tissue engineered constructs rely on solid pre-formed scaffolding materials, which require large incisions and extensive dissections for placement at the defect site. Thus, they are not suitable for minimally invasive techniques.The aim of this study was to develop a clinically relevant, easily moldable, bone tissue engineered construct (TEC), amenable to minimally invasive techniques, using human mesenchymal stromal cells (hMSC) and calcium phosphate micro particles in combination with an in-situ forming platelet rich plasma (PRP) gel obtained from human platelets. Most conventional TECs rely on seeding and culturing single cell suspensions of hMSCs on scaffolds. However, for generating TECs amenable to the minimally invasive approach, it was essential to aggregate the hMSCs in vitro prior to seeding them on the scaffolds as unaggregated MSCs did not generate any bone. 24 hours of in vitro aggregation was determined to be optimal for maintaining cell viability in vitro and bone formation in vivo. Moreover, no statistically significant difference was observed in the amount of bone formed when the TECs were implanted via an open approach or a minimally invasive route. TECs generated using MSCs from three different human donors generated new bone through the minimally invasive route in a reproducible manner, suggesting that these TECs could be a viable alternative to pre-formed scaffoldsemployed through an open surgery for treating bone defects. Page 2 of 35Tissue Engineering Part A eering new bone via a minimally invasive route using human bone marrow derived stromal cell aggregates, micro ceramic particles and human platelet rich plasma gel

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The Behavior of Human Mesenchymal Stem Cells in 3D Fibrin Clots: Dependence on Fibrinogen Concentration and Clot Structure

Cited by 211 publications

References 36 publications

Influencing biophysical properties of fibrin with buffer solutions

Influencing biophysical properties of fibrin with buffer solutions

Release of Bioactive Adeno-Associated Virus from Fibrin Scaffolds: Effects of Fibrin Glue Concentrations

Engineering New Bone via a Minimally Invasive Route Using Human Bone Marrow-Derived Stromal Cell Aggregates, Microceramic Particles, and Human Platelet-Rich Plasma Gel

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