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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

(A) Micrographs of HUVECs within agarose–gelatin–fibrinogen microcapsules at Day 0 and after their release. On Day 1, released HUVECs are seen attached and spread after their release onto gelatin-coated tissue culture plastic. By Day 2, several cells have migrated and have aligned themselves into a cord-like structure that is typical of HUVEC in vitro tubulogenesis behavior [27]. (B) Non-encapsulated HUVEVs control.
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jfb-06-00439-f007: (A) Micrographs of HUVECs within agarose–gelatin–fibrinogen microcapsules at Day 0 and after their release. On Day 1, released HUVECs are seen attached and spread after their release onto gelatin-coated tissue culture plastic. By Day 2, several cells have migrated and have aligned themselves into a cord-like structure that is typical of HUVEC in vitro tubulogenesis behavior [27]. (B) Non-encapsulated HUVEVs control.

Mentions: We have shown using human fibroblasts as a model cell line that cells can be very simply and effectively encapsulated within hydrogel microcapsules and subsequently released onto gelatin coated tissue culture plates. With a view to potential clinical application, we also showed that the methodologies developed were also applicable for endothelial cells, e.g., for revascularization of ischemic tissues such as heart muscle after a myocardial infraction, while HUVECs were more delicate and had a higher rate of cell death due to the encapsulation process (as shown in Figure 4). We observed that the released HUVECs retained their ability to migrate on the gelatin substratum to form cord-like structures that are precursors to the in vitro tubulogenesis (Figure 7), a behavior typical of HUVEC on gelatin [27]. This showed that the encapsulation did not adversely alter the behavior of the encapsulated cells, an important criterion for potential clinical application.


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)

(A) Micrographs of HUVECs within agarose–gelatin–fibrinogen microcapsules at Day 0 and after their release. On Day 1, released HUVECs are seen attached and spread after their release onto gelatin-coated tissue culture plastic. By Day 2, several cells have migrated and have aligned themselves into a cord-like structure that is typical of HUVEC in vitro tubulogenesis behavior [27]. (B) Non-encapsulated HUVEVs control.
© Copyright Policy
Related In: Results  -  Collection

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

jfb-06-00439-f007: (A) Micrographs of HUVECs within agarose–gelatin–fibrinogen microcapsules at Day 0 and after their release. On Day 1, released HUVECs are seen attached and spread after their release onto gelatin-coated tissue culture plastic. By Day 2, several cells have migrated and have aligned themselves into a cord-like structure that is typical of HUVEC in vitro tubulogenesis behavior [27]. (B) Non-encapsulated HUVEVs control.
Mentions: We have shown using human fibroblasts as a model cell line that cells can be very simply and effectively encapsulated within hydrogel microcapsules and subsequently released onto gelatin coated tissue culture plates. With a view to potential clinical application, we also showed that the methodologies developed were also applicable for endothelial cells, e.g., for revascularization of ischemic tissues such as heart muscle after a myocardial infraction, while HUVECs were more delicate and had a higher rate of cell death due to the encapsulation process (as shown in Figure 4). We observed that the released HUVECs retained their ability to migrate on the gelatin substratum to form cord-like structures that are precursors to the in vitro tubulogenesis (Figure 7), a behavior typical of HUVEC on gelatin [27]. This showed that the encapsulation did not adversely alter the behavior of the encapsulated cells, an important criterion for potential clinical application.

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