Encapsulation of macrophages enhances their retention and angiogenic potential

Francesca E. Ludwinski; Ashish S. Patel; Gopinath Damodaran; Jun Seok Cho; Joanna Furmston; Qingbo Xu; Suwan N. Jayasinghe; Alberto Smith; Bijan Modarai

doi:10.1038/s41536-019-0068-5

Encapsulation of macrophages enhances their retention and angiogenic potential

Francesca E. Ludwinski, Ashish S. Patel, Gopinath Damodaran, Jun Seok Cho, Joanna Furmston, Qingbo Xu, Suwan N. Jayasinghe, Alberto Smith, Bijan Modarai

UCL University College London

Research output: Contribution to journal › Article › peer-review

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Abstract

Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate-encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P=0.0001), and that this was associated both enhanced angiogenesis (P=0.02) and arteriogenesis (P=0.03), and an overall improvement in limb perfusion (P=0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.

Original language	English
Article number	6
Journal	NPJ Regenerative Medicine
Volume	4
DOIs	https://doi.org/10.1038/s41536-019-0068-5
Publication status	Published - 20 Mar 2019

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Encapsulation of macrophages enhances_LUDWINSKI_Accepted19December2018_GOLD AAMAccepted author manuscript, 284 KB

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title = "Encapsulation of macrophages enhances their retention and angiogenic potential",

abstract = "Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate-encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P=0.0001), and that this was associated both enhanced angiogenesis (P=0.02) and arteriogenesis (P=0.03), and an overall improvement in limb perfusion (P=0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.",

author = "Ludwinski, {Francesca E.} and Patel, {Ashish S.} and Gopinath Damodaran and Cho, {Jun Seok} and Joanna Furmston and Qingbo Xu and Jayasinghe, {Suwan N.} and Alberto Smith and Bijan Modarai",

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doi = "10.1038/s41536-019-0068-5",

language = "English",

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T1 - Encapsulation of macrophages enhances their retention and angiogenic potential

AU - Ludwinski, Francesca E.

AU - Patel, Ashish S.

AU - Damodaran, Gopinath

AU - Cho, Jun Seok

AU - Furmston, Joanna

AU - Xu, Qingbo

AU - Jayasinghe, Suwan N.

AU - Smith, Alberto

AU - Modarai, Bijan

PY - 2019/3/20

Y1 - 2019/3/20

N2 - Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate-encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P=0.0001), and that this was associated both enhanced angiogenesis (P=0.02) and arteriogenesis (P=0.03), and an overall improvement in limb perfusion (P=0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.

AB - Cell therapies to treat critical limb ischaemia have demonstrated only modest results in clinical trials, and this has been partly attributed to poor cell retention following their delivery directly into the ischaemic limb. The aim of this study was to determine whether alginate-encapsulation of therapeutic pro-angio/arteriogenic macrophages enhances their retention and ultimately improves limb perfusion. A reproducible GMP-compliant method for generating 300µm alginate capsules was developed to encapsulate pro-angio/arteriogenic macrophages. Longitudinal analysis revealed no detrimental effect of encapsulation on cell number or viability in vitro, and macrophages retained their pro-angio/arteriogenic phenotype. Intramuscular delivery of encapsulated macrophages into the murine ischaemic hindlimb demonstrated increased cell retention compared with injection of naked cells (P=0.0001), and that this was associated both enhanced angiogenesis (P=0.02) and arteriogenesis (P=0.03), and an overall improvement in limb perfusion (P=0.0001). Alginate encapsulation of pro-angio/arteriogenic macrophages enhances cell retention and subsequent limb reperfusion in vivo. Encapsulation may therefore represent a means of improving the efficacy of cell-based therapies currently under investigation for the treatment of limb ischaemia.

U2 - 10.1038/s41536-019-0068-5

DO - 10.1038/s41536-019-0068-5

M3 - Article

SN - 2057-3995

VL - 4

JO - NPJ Regenerative Medicine

JF - NPJ Regenerative Medicine

M1 - 6

ER -

Encapsulation of macrophages enhances their retention and angiogenic potential

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