Stem cell recruitment and angiogenesis of neuropeptide substance P coupled with self-assembling peptide nanofiber in a mouse hind limb ischemia model

Ji Hyun Kim, Youngmee Jung, Byung Soo Kim, Soo Hyun Kim

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

For the successful treatment of ischemia, it is important to resupply sufficient blood into ischemic regions by inducing angiogenesis. Many stem cell transplantation studies have been reported to enhance angiogenesis, especially those relating to mesenchymal stem cells (MSCs); however cell transplantation has a number of limitations, such as the low rate of cell survival and donor cell shortage. In this study, we developed bioactive peptides by immobilizing substance P into self-assembling peptides, and their MSCs recruiting ability and therapeutic effects were evaluated by using ischemic hind limb models. Limb ischemia was produced in athymic mice, and 1% (wt/vol) peptides were injected into ischemic sites (n = 6 in each group: ischemia, substance P, RADA16-II, RADA16-II + substance P, and RADA16-II + RADA-SP (bioactive peptides)). The tissues were harvested for histological analysis and tissue perfusion measurement at 1, 3, 7, and 28 days after injection. We observed that bioactive peptides assembled themselves (<10 nm nanofibers) and formed 3-dimensional (3D) microenvironments within ischemic regions. In the animal study, it was observed that by applying bioactive peptides, substance P continued to be released at 28 days, and consequently, MSCs were successfully recruited into ischemic regions. Bioactive peptides could prevent fibrosis, promote neovascularization, enhance tissue perfusion, and prevent limb salvages. Our results demonstrated that bioactive peptides are one of the most powerful tools for the treatment of ischemia, through their recruitment of autologous MSCs and promotion of angiogenesis without cells transplantation.

Original languageEnglish
Pages (from-to)1657-1668
Number of pages12
JournalBiomaterials
Volume34
Issue number6
DOIs
Publication statusPublished - 2013 Feb 1

Fingerprint

Nanofibers
Substance P
Stem cells
Neuropeptides
Peptides
Stem Cells
Ischemia
Extremities
Mesenchymal Stromal Cells
Cell Transplantation
Tissue
Perfusion
Limb Salvage
Salvaging
Stem Cell Transplantation
Therapeutic Uses
Nude Mice
Cell Survival
Fibrosis
Animals

Keywords

  • Angiogenesis
  • Bioactive peptides
  • Ischemia
  • Mesenchymal stem cells
  • Substance P

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Stem cell recruitment and angiogenesis of neuropeptide substance P coupled with self-assembling peptide nanofiber in a mouse hind limb ischemia model. / Kim, Ji Hyun; Jung, Youngmee; Kim, Byung Soo; Kim, Soo Hyun.

In: Biomaterials, Vol. 34, No. 6, 01.02.2013, p. 1657-1668.

Research output: Contribution to journalArticle

Kim, Ji Hyun ; Jung, Youngmee ; Kim, Byung Soo ; Kim, Soo Hyun. / Stem cell recruitment and angiogenesis of neuropeptide substance P coupled with self-assembling peptide nanofiber in a mouse hind limb ischemia model. In: Biomaterials. 2013 ; Vol. 34, No. 6. pp. 1657-1668.
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