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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

Cell viability at weeks 0 and 3.(A) Live-dead images of the 10M/mL rBMSC aggregates and controls. (B) Live-dead images of the 20M/mL rBMSC aggregates and controls. Scale bar = 100 μm.
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pone.0141479.g002: Cell viability at weeks 0 and 3.(A) Live-dead images of the 10M/mL rBMSC aggregates and controls. (B) Live-dead images of the 20M/mL rBMSC aggregates and controls. Scale bar = 100 μm.

Mentions: Cell viability overall was quite high. Compared to the 20M aggregate groups, the 10M LA and 10M HA grouops had relatively higher densities of live cells at week 3 than at week 0 (Fig 2). 20M aggregates exhibited some cell death right from week 0, and all of the HA groups had more visible dead cells than the LA groups for both 10M and 20M at week 3 compared to week 0. Among the aggregate groups, 20M HA, 10M HA, and 20M LA had condensed regions of cell death at the aggregate periphery at week 0, whereas cell death was distributed throughout the aggregate at week 3. There was no noticeable increase in aggregate diameter over the 3 weeks for any of the groups. There was increased cell death in week 3 in 20M HA CS compared to week 0, but lesser cell death compared to aggregates.


Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels.

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

Cell viability at weeks 0 and 3.(A) Live-dead images of the 10M/mL rBMSC aggregates and controls. (B) Live-dead images of the 20M/mL rBMSC aggregates and controls. Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0141479.g002: Cell viability at weeks 0 and 3.(A) Live-dead images of the 10M/mL rBMSC aggregates and controls. (B) Live-dead images of the 20M/mL rBMSC aggregates and controls. Scale bar = 100 μm.
Mentions: Cell viability overall was quite high. Compared to the 20M aggregate groups, the 10M LA and 10M HA grouops had relatively higher densities of live cells at week 3 than at week 0 (Fig 2). 20M aggregates exhibited some cell death right from week 0, and all of the HA groups had more visible dead cells than the LA groups for both 10M and 20M at week 3 compared to week 0. Among the aggregate groups, 20M HA, 10M HA, and 20M LA had condensed regions of cell death at the aggregate periphery at week 0, whereas cell death was distributed throughout the aggregate at week 3. There was no noticeable increase in aggregate diameter over the 3 weeks for any of the groups. There was increased cell death in week 3 in 20M HA CS compared to week 0, but lesser cell death compared to aggregates.

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