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Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels.

Sridharan B, Lin SM, Hwu AT, Laflin AD, Detamore MS - PLoS ONE (2015)

Bottom Line: Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis.Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis.Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance.

View Article: PubMed Central - PubMed

Affiliation: Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas, United States of America.

ABSTRACT
There are a variety of exciting hydrogel technologies being explored for cartilage regenerative medicine. Our overall goal is to explore whether using stem cells in an aggregate form may be advantageous in these applications. 3D stem cell aggregates hold great promise as they may recapitulate the in vivo skeletal tissue condensation, a property that is not typically observed in 2D culture. We considered two different stem cell sources, human umbilical cord Wharton's jelly cells (hWJCs, currently being used in clinical trials) and rat bone marrow-derived mesenchymal stem cells (rBMSCs). The objective of the current study was to compare the influence of cell phenotype, aggregate size, and aggregate number on chondrogenic differentiation in a generic hydrogel (agarose) platform. Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis. Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis. Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance.

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Related in: MedlinePlus

Representative images for immunohistochemistry analysis for collagen I, collagen II, and aggrecan staining for hWJC groups at week 0, 2, and 3.The 10M LA and 20M HA groups at week 0 displayed the highest staining intensity for aggrecan and 20M LA group at week 3 displayed the highest staining intensity for aggrecan. Scale bar = 200 μm.
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pone.0141479.g010: Representative images for immunohistochemistry analysis for collagen I, collagen II, and aggrecan staining for hWJC groups at week 0, 2, and 3.The 10M LA and 20M HA groups at week 0 displayed the highest staining intensity for aggrecan and 20M LA group at week 3 displayed the highest staining intensity for aggrecan. Scale bar = 200 μm.

Mentions: Collagen I stain was prominent in the center of the aggregate for the 20M LA group at week 3 (Fig 10). Collagen I did not increase in staining intensity over the 3 week period except for the 10M LA and 20M LA group, where the collagen I staining was highest at week 3. 20M HA showed highest collagen II staining at week 3. Aggrecan presented a very interesting staining pattern in the 10M LA and 20M HA groups, as both of these groups had starting aggrecan staining at week 0 to be the most intense (throughout the aggregate) and at week 3, staining was localized to specific patches near the center (10M LA) and around the periphery (20M HA). The 20M LA group were also striking for its intense aggrecan staining at week 3.


Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels.

Sridharan B, Lin SM, Hwu AT, Laflin AD, Detamore MS - PLoS ONE (2015)

Representative images for immunohistochemistry analysis for collagen I, collagen II, and aggrecan staining for hWJC groups at week 0, 2, and 3.The 10M LA and 20M HA groups at week 0 displayed the highest staining intensity for aggrecan and 20M LA group at week 3 displayed the highest staining intensity for aggrecan. Scale bar = 200 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697858&req=5

pone.0141479.g010: Representative images for immunohistochemistry analysis for collagen I, collagen II, and aggrecan staining for hWJC groups at week 0, 2, and 3.The 10M LA and 20M HA groups at week 0 displayed the highest staining intensity for aggrecan and 20M LA group at week 3 displayed the highest staining intensity for aggrecan. Scale bar = 200 μm.
Mentions: Collagen I stain was prominent in the center of the aggregate for the 20M LA group at week 3 (Fig 10). Collagen I did not increase in staining intensity over the 3 week period except for the 10M LA and 20M LA group, where the collagen I staining was highest at week 3. 20M HA showed highest collagen II staining at week 3. Aggrecan presented a very interesting staining pattern in the 10M LA and 20M HA groups, as both of these groups had starting aggrecan staining at week 0 to be the most intense (throughout the aggregate) and at week 3, staining was localized to specific patches near the center (10M LA) and around the periphery (20M HA). The 20M LA group were also striking for its intense aggrecan staining at week 3.

Bottom Line: Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis.Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis.Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance.

View Article: PubMed Central - PubMed

Affiliation: Bioengineering Graduate Program, University of Kansas, Lawrence, Kansas, United States of America.

ABSTRACT
There are a variety of exciting hydrogel technologies being explored for cartilage regenerative medicine. Our overall goal is to explore whether using stem cells in an aggregate form may be advantageous in these applications. 3D stem cell aggregates hold great promise as they may recapitulate the in vivo skeletal tissue condensation, a property that is not typically observed in 2D culture. We considered two different stem cell sources, human umbilical cord Wharton's jelly cells (hWJCs, currently being used in clinical trials) and rat bone marrow-derived mesenchymal stem cells (rBMSCs). The objective of the current study was to compare the influence of cell phenotype, aggregate size, and aggregate number on chondrogenic differentiation in a generic hydrogel (agarose) platform. Despite being differing cell sources, both rBMSC and hWJC aggregates were consistent in outperforming cell suspension control groups in biosynthesis and chondrogenesis. Higher cell density impacted biosynthesis favorably, and the number of aggregates positively influenced chondrogenesis. Therefore, we recommend that investigators employing hydrogels consider using cells in an aggregate form for enhanced chondrogenic performance.

Show MeSH
Related in: MedlinePlus