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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

Schematic diagram illustrating (A) the concept of cell delivery and release with temperature responsive microcapsules and (B) the hypothesized mechanism of cell release from a composite temperature responsive hydrogel comprising two materials with different phase transition temperatures.
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jfb-06-00439-f001: Schematic diagram illustrating (A) the concept of cell delivery and release with temperature responsive microcapsules and (B) the hypothesized mechanism of cell release from a composite temperature responsive hydrogel comprising two materials with different phase transition temperatures.

Mentions: In this study, our goal was to build upon and refine the agarose-fibrinogen microcapsules with temperature responsive hydrogel to allow delivery, as well as release of encapsulated cells for future therapeutic application. We tested the hypothesis that the combination of two biomaterials such as low-gelling temperature agarose (gels at <30 °C and melts at >60 °C) and gelatin (melts at >35 °C), which possess different phase transition temperatures from gel to sol, will result in a temperature responsive composite microcapsule that can be used to temporarily encase cells for controlled delivery. For example, at the physiological temperature of 37 °C, low-gelling temperature agarose exists as a solid gel, while gelatin melts, entering the liquid phase and thereby destabilizing the resulting capsule and allowing the encased cells to escape (Figure 1). We verified the hypothesis by fabricating microcapsules of agarose and gelatin, with and without added fibrinogen, and testing these as cell delivery systems that allowed for controlled cell release, using human fibroblast as model cells. We then confirmed the utility of this tool with human umbilical vein endothelial cells (HUVECs) as a model of therapeutic angiogenic cells.


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)

Schematic diagram illustrating (A) the concept of cell delivery and release with temperature responsive microcapsules and (B) the hypothesized mechanism of cell release from a composite temperature responsive hydrogel comprising two materials with different phase transition temperatures.
© Copyright Policy
Related In: Results  -  Collection

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

jfb-06-00439-f001: Schematic diagram illustrating (A) the concept of cell delivery and release with temperature responsive microcapsules and (B) the hypothesized mechanism of cell release from a composite temperature responsive hydrogel comprising two materials with different phase transition temperatures.
Mentions: In this study, our goal was to build upon and refine the agarose-fibrinogen microcapsules with temperature responsive hydrogel to allow delivery, as well as release of encapsulated cells for future therapeutic application. We tested the hypothesis that the combination of two biomaterials such as low-gelling temperature agarose (gels at <30 °C and melts at >60 °C) and gelatin (melts at >35 °C), which possess different phase transition temperatures from gel to sol, will result in a temperature responsive composite microcapsule that can be used to temporarily encase cells for controlled delivery. For example, at the physiological temperature of 37 °C, low-gelling temperature agarose exists as a solid gel, while gelatin melts, entering the liquid phase and thereby destabilizing the resulting capsule and allowing the encased cells to escape (Figure 1). We verified the hypothesis by fabricating microcapsules of agarose and gelatin, with and without added fibrinogen, and testing these as cell delivery systems that allowed for controlled cell release, using human fibroblast as model cells. We then confirmed the utility of this tool with human umbilical vein endothelial cells (HUVECs) as a model of therapeutic angiogenic cells.

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