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Controlled Delivery of Human Cells by Temperature Responsive Microcapsules.

Mak WC, Olesen K, Sivlér P, Lee CJ, Moreno-Jimenez I, Edin J, Courtman D, Skog M, Griffith M - J Funct Biomater (2015)

Bottom Line: However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into.Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line-human umbilical vein endothelial cells (HUVECs).While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

View Article: PubMed Central - PubMed

Affiliation: Integrative Regenerative Medicine Centre, Department of Clinical and Experimental Medicine, Linköping University, SE58185, Linköping, Sweden. mamak@ifm.liu.se.

ABSTRACT
Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line-human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

No MeSH data available.


Related in: MedlinePlus

The relatively cell viability of (A) encapsulated human fibroblast cells and (B) encapsulated HUVECs over time, within the agarose–gelatin–fibrinogen microcapsules. Time points with a connecting line over their bars were not found to be significantly different. Bars not connected by lines were found to be significantly different (GLM using Tukey post hoc, p ≤ 0.05).
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jfb-06-00439-f003: The relatively cell viability of (A) encapsulated human fibroblast cells and (B) encapsulated HUVECs over time, within the agarose–gelatin–fibrinogen microcapsules. Time points with a connecting line over their bars were not found to be significantly different. Bars not connected by lines were found to be significantly different (GLM using Tukey post hoc, p ≤ 0.05).

Mentions: With human fibroblasts, the encapsulation process resulted in 19.9% dead cells (at Day 0). With HUVECs, which are more sensitive cells, the encapsulation resulted in 30.1% dead cells. Between Days 0 and 1, the ratio of dead fibroblasts had increased by 4.9% and from Day 1 to Day 2, the ratio of dead cells increased a further 7.8%. For the HUVEC cells, the ratio of dead cells increased by 26.6% between Day 0 and Day 1, and there was a further 2.2% increase in the ratio of dead HUVEC cells between Day 1 and 2 (Figure 3). There was a significant difference between cell viability of the two different cell types (General linear model/GLM, p ≤ 0.01). Both cell types had significant differences between time points (GLM, p ≤ 0.01), the dynamics of the overtime change differed between cell types. Fibroblast survival did not show a significant difference between Day 0 and Day 1; at Day 2 there was, however, a significantly smaller ratio of live cells. The HUVEC cells on the other hand, showed a significant loss of live cells between Day 0 and Day 1. However, between Day 1 and 2 there was no significant further loss.


Controlled Delivery of Human Cells by Temperature Responsive Microcapsules.

Mak WC, Olesen K, Sivlér P, Lee CJ, Moreno-Jimenez I, Edin J, Courtman D, Skog M, Griffith M - J Funct Biomater (2015)

The relatively cell viability of (A) encapsulated human fibroblast cells and (B) encapsulated HUVECs over time, within the agarose–gelatin–fibrinogen microcapsules. Time points with a connecting line over their bars were not found to be significantly different. Bars not connected by lines were found to be significantly different (GLM using Tukey post hoc, p ≤ 0.05).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493523&req=5

jfb-06-00439-f003: The relatively cell viability of (A) encapsulated human fibroblast cells and (B) encapsulated HUVECs over time, within the agarose–gelatin–fibrinogen microcapsules. Time points with a connecting line over their bars were not found to be significantly different. Bars not connected by lines were found to be significantly different (GLM using Tukey post hoc, p ≤ 0.05).
Mentions: With human fibroblasts, the encapsulation process resulted in 19.9% dead cells (at Day 0). With HUVECs, which are more sensitive cells, the encapsulation resulted in 30.1% dead cells. Between Days 0 and 1, the ratio of dead fibroblasts had increased by 4.9% and from Day 1 to Day 2, the ratio of dead cells increased a further 7.8%. For the HUVEC cells, the ratio of dead cells increased by 26.6% between Day 0 and Day 1, and there was a further 2.2% increase in the ratio of dead HUVEC cells between Day 1 and 2 (Figure 3). There was a significant difference between cell viability of the two different cell types (General linear model/GLM, p ≤ 0.01). Both cell types had significant differences between time points (GLM, p ≤ 0.01), the dynamics of the overtime change differed between cell types. Fibroblast survival did not show a significant difference between Day 0 and Day 1; at Day 2 there was, however, a significantly smaller ratio of live cells. The HUVEC cells on the other hand, showed a significant loss of live cells between Day 0 and Day 1. However, between Day 1 and 2 there was no significant further loss.

Bottom Line: However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into.Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line-human umbilical vein endothelial cells (HUVECs).While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

View Article: PubMed Central - PubMed

Affiliation: Integrative Regenerative Medicine Centre, Department of Clinical and Experimental Medicine, Linköping University, SE58185, Linköping, Sweden. mamak@ifm.liu.se.

ABSTRACT
Cell therapy is one of the most promising areas within regenerative medicine. However, its full potential is limited by the rapid loss of introduced therapeutic cells before their full effects can be exploited, due in part to anoikis, and in part to the adverse environments often found within the pathologic tissues that the cells have been grafted into. Encapsulation of individual cells has been proposed as a means of increasing cell viability. In this study, we developed a facile, high throughput method for creating temperature responsive microcapsules comprising agarose, gelatin and fibrinogen for delivery and subsequent controlled release of cells. We verified the hypothesis that composite capsules combining agarose and gelatin, which possess different phase transition temperatures from solid to liquid, facilitated the destabilization of the capsules for cell release. Cell encapsulation and controlled release was demonstrated using human fibroblasts as model cells, as well as a therapeutically relevant cell line-human umbilical vein endothelial cells (HUVECs). While such temperature responsive cell microcapsules promise effective, controlled release of potential therapeutic cells at physiological temperatures, further work will be needed to augment the composition of the microcapsules and optimize the numbers of cells per capsule prior to clinical evaluation.

No MeSH data available.


Related in: MedlinePlus