Human Mesenchymal Stem Cell Proliferation and Osteogenic Differentiation in Fibrin Gels in Vitro

Catelas, Isabelle; Sese, Nadjah; Wu, Benjamin M.; Dunn, James C.Y.; Helgerson, Sam; Tawil, Bill

doi:10.1089/ten.2006.12.ft-97

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…Just as important, the material must support differentiation of progenitor cells down the osteogenic lineage. Previously, fibrin materials have demonstrated the ability to induce osteogenesis of hMSCs 48. Similarly, we found that gene expression of hMSCs encapsulated within CS‐BM and exposed to osteogenic media conditions was consistent with that of cells undergoing osteogenesis.…”

Section: Discussionsupporting

confidence: 80%

An orthopedic tissue adhesive for targeted delivery of intraoperative biologics

Simson

Crist

Strehin

et al. 2012

Journal Orthopaedic Research

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Tissue adhesives can bind together damaged tissues and serve as tools to deliver and localize therapeutics to facilitate regeneration. One emerging therapeutic trend in orthopedics is the use of intraoperative biologics (IOB), such as bone marrow (BM) and platelet-rich plasma (PRP), to stimulate healing. Here, we introduce the application of the biomaterial chondroitin sulfate succinimidyl succinate (CS-NHS) to deliver IOB in a hydrogel adhesive. We demonstrate the biomaterial's ability to bind various tissue types and its cellular biocompatibility with encapsulated human mesenchymal stem cells (hMSCs). Further, we examine in detail the CS-NHS adhesive combined with BM aspirate for use in bone applications. hMSCs were encapsulated in CS-BM and cultured for 5 weeks in osteogenic medium. Quantitative RT-PCR demonstrated osteogenesis via upregulation of the osteogenic transcription factor Runx2 and bone markers alkaline phosphatase and osteocalcin. Significant deposition of calcium and osteocalcin was detected using biochemical, histological, and immunohistochemical techniques. Shear testing demonstrated that the CS-BM adhesive exhibited an adhesive strength approximately an order of magnitude stronger than fibrin glue and approaching that of a cyanoacrylate adhesive. These results indicate that CS-NHS is a promising delivery tool for IOB in orthopedic applications requiring a strong, degradable, and biocompatible adhesive that supports bone growth. ß

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Section: Discussionsupporting

confidence: 80%

An orthopedic tissue adhesive for targeted delivery of intraoperative biologics

Simson

Crist

Strehin

et al. 2012

Journal Orthopaedic Research

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“…In this particular study, we focused on MSC encapsulation within fibrin, in part, because fibrin is a widely used material, 19 which has been shown to promote cell survival and proliferation both in vitro and in vivo. [20][21][22][23] There is compelling evidence that fibrin supports the delivery of stem cells, such as bone marrow mononuclear cells 24,25 and human MSCs, 20,26,27 and stimulates the MSC differentiation toward osteogenic and chondrogenic differentiation. [27][28][29] In our own work, we have used fibrin extensively as an extracellular matrix analog capable of supporting capillary morphogenesis in vitro [30][31][32][33] and neovascularization in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…[20][21][22][23] There is compelling evidence that fibrin supports the delivery of stem cells, such as bone marrow mononuclear cells 24,25 and human MSCs, 20,26,27 and stimulates the MSC differentiation toward osteogenic and chondrogenic differentiation. [27][28][29] In our own work, we have used fibrin extensively as an extracellular matrix analog capable of supporting capillary morphogenesis in vitro [30][31][32][33] and neovascularization in vivo. 31,34 We have also shown that cocultures of MSCs and endothelial cells in 3D fibrin hydrogels readily form pericyte-invested capillary networks, 32,35,36 which have prompted our efforts to better understand how the perivascular location of MSCs may influence their phenotype.…”

Section: Introductionmentioning

confidence: 99%

A Safe and Efficient Method to Retrieve Mesenchymal Stem Cells from Three-Dimensional Fibrin Gels

Carrion

Janson

Kong

et al. 2014

Tissue Engineering Part C: Methods

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Mesenchymal stem cells (MSCs) display multipotent characteristics that make them ideal for potential therapeutic applications. MSCs are typically cultured as monolayers on tissue culture plastic, but there is increasing evidence suggesting that they may lose their multipotency over time in vitro and eventually cease to retain any resemblance to in vivo resident MSCs. Three-dimensional (3D) culture systems that more closely recapitulate the physiological environment of MSCs and other cell types are increasingly explored for their capacity to support and maintain the cell phenotypes. In much of our own work, we have utilized fibrin, a natural protein-based material that serves as the provisional extracellular matrix during wound healing. Fibrin has proven to be useful in numerous tissue engineering applications and has been used clinically as a hemostatic material. Its rapid self-assembly driven by thrombin-mediated alteration of fibrinogen makes fibrin an attractive 3D substrate, in which cells can adhere, spread, proliferate, and undergo complex morphogenetic programs. However, there is a significant need for simple cost-effective methods to safely retrieve cells encapsulated within fibrin hydrogels to perform additional analyses or use the cells for therapy. Here, we present a safe and efficient protocol for the isolation of MSCs from 3D fibrin gels. The key ingredient of our successful extraction method is nattokinase, a serine protease of the subtilisin family that has a strong fibrinolytic activity. Our data show that MSCs recovered from 3D fibrin gels using nattokinase are not only viable but also retain their proliferative and multilineage potentials. Demonstrated for MSCs, this method can be readily adapted to retrieve any other cell type from 3D fibrin gel constructs for various applications, including expansion, bioassays, and in vivo implantation.

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“…Lower concentrations of fibrinogen might have facilitated cell elongation and proliferation as compared to higher concentrations as observed in a previous study (Catelas et al . ). It was reported that delivering of DPSCs in fibrin gel into immature human root canals resulted in ectopic pulp‐like tissue formation in rats (Ruangsawasdi et al .…”

Section: Discussionmentioning

confidence: 97%