Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo

Ryo Hotta, Lily S. Cheng, Hannah K. Graham, N. Nagy, Jaime Belkind-Gerson, George Mattheolabakis, Mansoor M. Amiji, Allan M. Goldstein

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Cell therapy offers an innovative approach for treating enteric neuropathies. Postnatal gut-derived enteric neural stem/progenitor cells (ENSCs) represent a potential autologous source, but have a limited capacity for proliferation and neuronal differentiation. Since serotonin (5-HT) promotes enteric neuronal growth during embryonic development, we hypothesized that serotonin receptor agonism would augment growth of neurons from transplanted ENSCs. Postnatal ENSCs were isolated from 2 to 4 week-old mouse colon and cultured with 5-HT4 receptor agonist (RS67506)-loaded liposomal nanoparticles. ENSCs were co-cultured with mouse colon explants in the presence of RS67506-loaded (n = 3) or empty nanoparticles (n = 3). ENSCs were also transplanted into mouse rectum in vivo with RS67506-loaded (n = 8) or blank nanoparticles (n = 4) confined in a thermosensitive hydrogel, Pluronic F-127. Neuronal density and proliferation were analyzed immunohistochemically. Cultured ENSCs gave rise to significantly more neurons in the presence of RS67506-loaded nanoparticles. Similarly, colon explants had significantly increased neuronal density when RS67506-loaded nanoparticles were present. Finally, following in vivo cell delivery, co-transplantation of ENSCs with 5-HT4 receptor agonist-loaded nanoparticles led to significantly increased neuronal density and proliferation. We conclude that optimization of postnatal ENSCs can support their use in cell-based therapies for neurointestinal diseases.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalBiomaterials
Volume88
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Serotonin 5-HT4 Receptor Agonists
Neural Stem Cells
Hydrogel
Cell proliferation
Stem cells
Hydrogels
Nanoparticles
Cell Differentiation
Stem Cells
Transplantation
Cell Proliferation
Receptors, Serotonin, 5-HT4
Colon
Cell- and Tissue-Based Therapy
Neurons
Serotonin
Intestinal Pseudo-Obstruction
Poloxamer
Serotonin Receptors
Growth

Keywords

  • 5-HT receptor agonist
  • Cell therapy
  • Enteric neuropathies
  • Liposomal nanoparticles
  • Serotonin
  • Thermosensitive hydrogel

ASJC Scopus subject areas

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

Cite this

Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo. / Hotta, Ryo; Cheng, Lily S.; Graham, Hannah K.; Nagy, N.; Belkind-Gerson, Jaime; Mattheolabakis, George; Amiji, Mansoor M.; Goldstein, Allan M.

In: Biomaterials, Vol. 88, 01.05.2016, p. 1-11.

Research output: Contribution to journalArticle

Hotta, Ryo ; Cheng, Lily S. ; Graham, Hannah K. ; Nagy, N. ; Belkind-Gerson, Jaime ; Mattheolabakis, George ; Amiji, Mansoor M. ; Goldstein, Allan M. / Delivery of enteric neural progenitors with 5-HT4 agonist-loaded nanoparticles and thermosensitive hydrogel enhances cell proliferation and differentiation following transplantation in vivo. In: Biomaterials. 2016 ; Vol. 88. pp. 1-11.
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