Limits...
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.

Show MeSH

Related in: MedlinePlus

Gene expression of Collagen I, Aggrecan and SOX9 for rBMSC groups at week 0, 2, and 3.There was significant increase in the SOX9 and Aggrecan value at week 2 and 3 for 20 M HA group, compared to the controls. Values are reported as mean ± standard deviation, n = 4. (*) represents statistically significant difference over the week 0 value. (#) represents statistically significant highest value of the group (**) represents statistically significant difference from the control at that time point. (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4697858&req=5

pone.0141479.g007: Gene expression of Collagen I, Aggrecan and SOX9 for rBMSC groups at week 0, 2, and 3.There was significant increase in the SOX9 and Aggrecan value at week 2 and 3 for 20 M HA group, compared to the controls. Values are reported as mean ± standard deviation, n = 4. (*) represents statistically significant difference over the week 0 value. (#) represents statistically significant highest value of the group (**) represents statistically significant difference from the control at that time point. (p < 0.05).

Mentions: The 10M LA CS group (Fig 7A & 7B) had a 3.5-fold increase in expression in collagen I gene expression from week 0 to week 2, and the 20M LA CS group had a 10.2-fold increase in collagen I expression from week 0 to week 3 (p < 0.05). The 10M HA CS group did not show any significant increase in gene expression over time, but the 20M HA CS group had a 97.5% increase in gene expression from week 0 to week 2 (p < 0.05). Among the aggregate groups, there were two significant changes in gene expression over time. First, the 20M LA group had a 5.6-fold increase at week 2 compared to week 0 and no significant increase at week 3 (p < 0.05). Second, the 10M HA group had a 3.6-fold increase in gene expression at week 2 compared to week 0 and no significant increase at week 3 (p < 0.05). The other aggregate groups (10M LA and 20M HA) did not show statistically significant changes over time. In comparing the aggregate and corresponding CS control groups, at week 3, the 10M HA group had a 1.7-fold higher collagen I expression compared to its respective CS control group (p < 0.05).


Stem Cells in Aggregate Form to Enhance Chondrogenesis in Hydrogels.

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

Gene expression of Collagen I, Aggrecan and SOX9 for rBMSC groups at week 0, 2, and 3.There was significant increase in the SOX9 and Aggrecan value at week 2 and 3 for 20 M HA group, compared to the controls. Values are reported as mean ± standard deviation, n = 4. (*) represents statistically significant difference over the week 0 value. (#) represents statistically significant highest value of the group (**) represents statistically significant difference from the control at that time point. (p < 0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0141479.g007: Gene expression of Collagen I, Aggrecan and SOX9 for rBMSC groups at week 0, 2, and 3.There was significant increase in the SOX9 and Aggrecan value at week 2 and 3 for 20 M HA group, compared to the controls. Values are reported as mean ± standard deviation, n = 4. (*) represents statistically significant difference over the week 0 value. (#) represents statistically significant highest value of the group (**) represents statistically significant difference from the control at that time point. (p < 0.05).
Mentions: The 10M LA CS group (Fig 7A & 7B) had a 3.5-fold increase in expression in collagen I gene expression from week 0 to week 2, and the 20M LA CS group had a 10.2-fold increase in collagen I expression from week 0 to week 3 (p < 0.05). The 10M HA CS group did not show any significant increase in gene expression over time, but the 20M HA CS group had a 97.5% increase in gene expression from week 0 to week 2 (p < 0.05). Among the aggregate groups, there were two significant changes in gene expression over time. First, the 20M LA group had a 5.6-fold increase at week 2 compared to week 0 and no significant increase at week 3 (p < 0.05). Second, the 10M HA group had a 3.6-fold increase in gene expression at week 2 compared to week 0 and no significant increase at week 3 (p < 0.05). The other aggregate groups (10M LA and 20M HA) did not show statistically significant changes over time. In comparing the aggregate and corresponding CS control groups, at week 3, the 10M HA group had a 1.7-fold higher collagen I expression compared to its respective CS control group (p < 0.05).

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