Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles

Fan Yang, Seung Woo Cho, Sun Mi Son, Said R. Bogatyrev, Deepika Singh, Jordan Green, Ying Mei, Sohyun Park, Suk Ho Bhang, Byung Soo Kim, Robert Langer, Daniel G. Anderson

Research output: Contribution to journalArticle

Abstract

Stem cells hold great potential as cell-based therapies to promote vascularization and tissue regeneration. However, the use of stem cells alone to promote angiogenesis remains limited because of insufficient expression of angiogenic factors and low cell viability after transplantation. Here, we have developed vascular endothelial growth factor (VEGF) high-expressing, transiently modified stem cells for the purposes of promoting angiogenesis. Nonviral, biodegradable polymeric nanoparticles were developed to deliver hVEGF gene to human mesenchymal stem cells (hMSCs) and human embryonic stem cell-derived cells (hESdCs). Treated stem cells demonstrated markedly enhanced hVEGF production, cell viability, and engraftment into target tissues. S.c. implantation of scaffolds seeded with VEGF-expressing stem cells (hMSCs and hESdCs) led to 2- to 4-fold-higher vessel densities 2 weeks after implantation, compared with control cells or cells transfected with VEGF by using Lipofectamine 2000, a leading commercial reagent. Four weeks after intramuscular injection into mouse ischemic hindlimbs, genetically modified hMSCs substantially enhanced angiogenesis and limb salvage while reducing muscle degeneration and tissue fibrosis. These results indicate that stem cells engineered with biodegradable polymer nanoparticles may be therapeutic tools for vascularizing tissue constructs and treating ischemic disease.

Original languageEnglish (US)
Pages (from-to)3317-3322
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number8
DOIs
StatePublished - Feb 23 2010
Externally publishedYes

Fingerprint

Genetic Engineering
Nanoparticles
Stem Cells
Mesenchymal Stromal Cells
Vascular Endothelial Growth Factor A
Cell Survival
Limb Salvage
Angiogenesis Inducing Agents
Intramuscular Injections
Hindlimb
Cell- and Tissue-Based Therapy
Regeneration
Polymers
Fibrosis
Transplantation
Muscles
Genes

Keywords

  • Biodegradable polymers
  • Ischemia
  • Nonviral gene delivery

ASJC Scopus subject areas

  • General

Cite this

Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles. / Yang, Fan; Cho, Seung Woo; Son, Sun Mi; Bogatyrev, Said R.; Singh, Deepika; Green, Jordan; Mei, Ying; Park, Sohyun; Bhang, Suk Ho; Kim, Byung Soo; Langer, Robert; Anderson, Daniel G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 8, 23.02.2010, p. 3317-3322.

Research output: Contribution to journalArticle

Yang, F, Cho, SW, Son, SM, Bogatyrev, SR, Singh, D, Green, J, Mei, Y, Park, S, Bhang, SH, Kim, BS, Langer, R & Anderson, DG 2010, 'Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles', Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 8, pp. 3317-3322. https://doi.org/10.1073/pnas.0905432106
Yang, Fan ; Cho, Seung Woo ; Son, Sun Mi ; Bogatyrev, Said R. ; Singh, Deepika ; Green, Jordan ; Mei, Ying ; Park, Sohyun ; Bhang, Suk Ho ; Kim, Byung Soo ; Langer, Robert ; Anderson, Daniel G. / Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 8. pp. 3317-3322.
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