Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells

Suk Ho Bhang, Seung-Woo Cho, Wan Geun La, Tae Jin Lee, Hee Seok Yang, Ah Young Sun, Sang Hong Baek, Jong Won Rhie, Byung Soo Kim

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

Stem cells offer significant therapeutic promise for the treatment of ischemic disease. However, stem cells transplanted into ischemic tissue exhibit limited therapeutic efficacy due to poor engraftment in vivo. Several strategies for improving the survival and engraftment of stem cells in ischemic tissue have been developed including transplantation in combination with growth factor delivery, genetic modification of stem cells, and the use of cell-transplantation scaffolds. Here, we demonstrate that human adipose-derived stromal cells (hADSCs) cultured and grafted as spheroids exhibit improved therapeutic efficacy for ischemia treatment. hADSCs were cultured in monolayer or spheroids. Spheroid cultures were more effective in preconditioning hADSCs to a hypoxic environment, upregulating hypoxia-adaptive signals (i.e., stromal cell-derived factor-1α and hypoxia-inducible factor-1α), inhibiting apoptosis, and enhancing secretion of both angiogenic and anti-apoptotic factors (i.e., hepatocyte growth factor, vascular endothelial growth factor, and fibroblast growth factor 2) compared to monolayer cultures. Moreover, cell harvesting following spheroid cultures avoided damage to extracellular matrices due to harsh proteolytic enzyme treatment, thereby preventing anoikis (apoptosis induced by a lack of cell-matrix interaction). Following intramuscular transplantation to ischemic hindlimbs of athymic mice, hADSC spheroids showed improved cell survival, angiogenic factor secretion, neovascularization, and limb survival as compared to hADSCs grafted as dissociated cells. Taken together, spheroid cultures precondition hADSCs to a hypoxic environment, and grafting hADSCs as spheroids to ischemic limbs improves therapeutic efficacy for ischemia treatment due to enhanced cell survival and paracrine effects. Spheroid-based cell delivery could be a simple and effective strategy for improving stem cell therapy for ischemic diseases, eliminating the need for growth factor delivery, biomaterial scaffolds or genetic modification.

Original languageEnglish
Pages (from-to)2734-2747
Number of pages14
JournalBiomaterials
Volume32
Issue number11
DOIs
Publication statusPublished - 2011 Apr 1

Fingerprint

Stromal Cells
Stem cells
Tissue
Stem Cells
Cell death
Scaffolds
Monolayers
Intercellular Signaling Peptides and Proteins
Cells
Apoptosis
Chemokine CXCL12
Hypoxia-Inducible Factor 1
Cell Survival
Hepatocyte Growth Factor
Angiogenesis Inducing Agents
Therapeutics
Ischemia
Extremities
Transplantation
Biocompatible Materials

All Science Journal Classification (ASJC) codes

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

Cite this

Bhang, Suk Ho ; Cho, Seung-Woo ; La, Wan Geun ; Lee, Tae Jin ; Yang, Hee Seok ; Sun, Ah Young ; Baek, Sang Hong ; Rhie, Jong Won ; Kim, Byung Soo. / Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. In: Biomaterials. 2011 ; Vol. 32, No. 11. pp. 2734-2747.
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Bhang, SH, Cho, S-W, La, WG, Lee, TJ, Yang, HS, Sun, AY, Baek, SH, Rhie, JW & Kim, BS 2011, 'Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells', Biomaterials, vol. 32, no. 11, pp. 2734-2747. https://doi.org/10.1016/j.biomaterials.2010.12.035

Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells. / Bhang, Suk Ho; Cho, Seung-Woo; La, Wan Geun; Lee, Tae Jin; Yang, Hee Seok; Sun, Ah Young; Baek, Sang Hong; Rhie, Jong Won; Kim, Byung Soo.

In: Biomaterials, Vol. 32, No. 11, 01.04.2011, p. 2734-2747.

Research output: Contribution to journalArticle

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T1 - Angiogenesis in ischemic tissue produced by spheroid grafting of human adipose-derived stromal cells

AU - Bhang, Suk Ho

AU - Cho, Seung-Woo

AU - La, Wan Geun

AU - Lee, Tae Jin

AU - Yang, Hee Seok

AU - Sun, Ah Young

AU - Baek, Sang Hong

AU - Rhie, Jong Won

AU - Kim, Byung Soo

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