In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three dimensional collagen scaffolds

Bellinda Bladergroen, B. Siebum, Kim G.C. Siebers-Vermeulen, Toin H. van Kuppevelt, Andreas A. Poot, Jan Feijen, Carl Figdor, Ruurd Torensma

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Implantable three-dimensional (3D) constructs to engineer tissue have great therapeutic potential in regenerative medicine and immunotherapy. However, autonomous recruitment of cells into the engineered scaffold in vivo is hampered by lack of attracting scaffolds. As a first step to engineering immune tissue, 3D collagen scaffolds were investigated for their ability to enhance in vivo recruitment and growth of various hematopoietic cells. Scaffolds containing immobilized heparin to trap the stem cell chemo-attractant stromal cell–derived factor 1 alpha (SDF1α) were implanted subcutaneously into C57Bl6 mice, and influx of cells was monitored using immunohistochemistry. Five weeks post-implantation, heparinized scaffolds were always populated by cells, but incorporating SDF1α considerably stimulated recruitment of cells. SDF1α could not exert this effect when the formation of a SDF1α gradient was abrogated. Scaffolds were mainly populated by CD11b+ and CD11c+ myeloid cells and fibroblasts. One week after implantation, scaffolds harbored only low numbers of cells. Apparently, not all CXCR4-expressing cells, like large numbers of granulocytes, migrate into the scaffold, but retransplantation of a 1-week-old scaffold from a CD45.2+ into a CD45.1+ mouse yielded a scaffold harboring mainly CD45.2+ cells after 5 weeks. These data confirm that only a few progenitor cells are recruited early after implantation. These cells then proliferate and differentiate along different lineages and determine the outcome after 5 weeks.
Original languageUndefined
Pages (from-to)1591-1599
JournalTissue engineering. Part A
Volume15
Issue number7
DOIs
Publication statusPublished - 2009

Keywords

  • IR-76377
  • METIS-264528

Cite this

Bladergroen, Bellinda ; Siebum, B. ; Siebers-Vermeulen, Kim G.C. ; van Kuppevelt, Toin H. ; Poot, Andreas A. ; Feijen, Jan ; Figdor, Carl ; Torensma, Ruurd. / In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three dimensional collagen scaffolds. In: Tissue engineering. Part A. 2009 ; Vol. 15, No. 7. pp. 1591-1599.
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abstract = "Implantable three-dimensional (3D) constructs to engineer tissue have great therapeutic potential in regenerative medicine and immunotherapy. However, autonomous recruitment of cells into the engineered scaffold in vivo is hampered by lack of attracting scaffolds. As a first step to engineering immune tissue, 3D collagen scaffolds were investigated for their ability to enhance in vivo recruitment and growth of various hematopoietic cells. Scaffolds containing immobilized heparin to trap the stem cell chemo-attractant stromal cell–derived factor 1 alpha (SDF1α) were implanted subcutaneously into C57Bl6 mice, and influx of cells was monitored using immunohistochemistry. Five weeks post-implantation, heparinized scaffolds were always populated by cells, but incorporating SDF1α considerably stimulated recruitment of cells. SDF1α could not exert this effect when the formation of a SDF1α gradient was abrogated. Scaffolds were mainly populated by CD11b+ and CD11c+ myeloid cells and fibroblasts. One week after implantation, scaffolds harbored only low numbers of cells. Apparently, not all CXCR4-expressing cells, like large numbers of granulocytes, migrate into the scaffold, but retransplantation of a 1-week-old scaffold from a CD45.2+ into a CD45.1+ mouse yielded a scaffold harboring mainly CD45.2+ cells after 5 weeks. These data confirm that only a few progenitor cells are recruited early after implantation. These cells then proliferate and differentiate along different lineages and determine the outcome after 5 weeks.",
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author = "Bellinda Bladergroen and B. Siebum and Siebers-Vermeulen, {Kim G.C.} and {van Kuppevelt}, {Toin H.} and Poot, {Andreas A.} and Jan Feijen and Carl Figdor and Ruurd Torensma",
year = "2009",
doi = "10.1089/ten.tea.2008.0348",
language = "Undefined",
volume = "15",
pages = "1591--1599",
journal = "Tissue engineering. Part A",
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In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three dimensional collagen scaffolds. / Bladergroen, Bellinda; Siebum, B.; Siebers-Vermeulen, Kim G.C.; van Kuppevelt, Toin H.; Poot, Andreas A.; Feijen, Jan; Figdor, Carl; Torensma, Ruurd.

In: Tissue engineering. Part A, Vol. 15, No. 7, 2009, p. 1591-1599.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - In vivo recruitment of hematopoietic cells using stromal cell-derived factor 1 alpha-loaded heparinized three dimensional collagen scaffolds

AU - Bladergroen, Bellinda

AU - Siebum, B.

AU - Siebers-Vermeulen, Kim G.C.

AU - van Kuppevelt, Toin H.

AU - Poot, Andreas A.

AU - Feijen, Jan

AU - Figdor, Carl

AU - Torensma, Ruurd

PY - 2009

Y1 - 2009

N2 - Implantable three-dimensional (3D) constructs to engineer tissue have great therapeutic potential in regenerative medicine and immunotherapy. However, autonomous recruitment of cells into the engineered scaffold in vivo is hampered by lack of attracting scaffolds. As a first step to engineering immune tissue, 3D collagen scaffolds were investigated for their ability to enhance in vivo recruitment and growth of various hematopoietic cells. Scaffolds containing immobilized heparin to trap the stem cell chemo-attractant stromal cell–derived factor 1 alpha (SDF1α) were implanted subcutaneously into C57Bl6 mice, and influx of cells was monitored using immunohistochemistry. Five weeks post-implantation, heparinized scaffolds were always populated by cells, but incorporating SDF1α considerably stimulated recruitment of cells. SDF1α could not exert this effect when the formation of a SDF1α gradient was abrogated. Scaffolds were mainly populated by CD11b+ and CD11c+ myeloid cells and fibroblasts. One week after implantation, scaffolds harbored only low numbers of cells. Apparently, not all CXCR4-expressing cells, like large numbers of granulocytes, migrate into the scaffold, but retransplantation of a 1-week-old scaffold from a CD45.2+ into a CD45.1+ mouse yielded a scaffold harboring mainly CD45.2+ cells after 5 weeks. These data confirm that only a few progenitor cells are recruited early after implantation. These cells then proliferate and differentiate along different lineages and determine the outcome after 5 weeks.

AB - Implantable three-dimensional (3D) constructs to engineer tissue have great therapeutic potential in regenerative medicine and immunotherapy. However, autonomous recruitment of cells into the engineered scaffold in vivo is hampered by lack of attracting scaffolds. As a first step to engineering immune tissue, 3D collagen scaffolds were investigated for their ability to enhance in vivo recruitment and growth of various hematopoietic cells. Scaffolds containing immobilized heparin to trap the stem cell chemo-attractant stromal cell–derived factor 1 alpha (SDF1α) were implanted subcutaneously into C57Bl6 mice, and influx of cells was monitored using immunohistochemistry. Five weeks post-implantation, heparinized scaffolds were always populated by cells, but incorporating SDF1α considerably stimulated recruitment of cells. SDF1α could not exert this effect when the formation of a SDF1α gradient was abrogated. Scaffolds were mainly populated by CD11b+ and CD11c+ myeloid cells and fibroblasts. One week after implantation, scaffolds harbored only low numbers of cells. Apparently, not all CXCR4-expressing cells, like large numbers of granulocytes, migrate into the scaffold, but retransplantation of a 1-week-old scaffold from a CD45.2+ into a CD45.1+ mouse yielded a scaffold harboring mainly CD45.2+ cells after 5 weeks. These data confirm that only a few progenitor cells are recruited early after implantation. These cells then proliferate and differentiate along different lineages and determine the outcome after 5 weeks.

KW - IR-76377

KW - METIS-264528

U2 - 10.1089/ten.tea.2008.0348

DO - 10.1089/ten.tea.2008.0348

M3 - Article

VL - 15

SP - 1591

EP - 1599

JO - Tissue engineering. Part A

JF - Tissue engineering. Part A

SN - 1937-3341

IS - 7

ER -