Long-term stability, functional competence, and safety of microencapsulated specific pathogen-free neonatal porcine Sertoli cells: a potential product for cell transplant therapy

Xenotransplantation. 2015 Jul-Aug;22(4):273-83. doi: 10.1111/xen.12175. Epub 2015 Jul 2.

Abstract

Background: Porcine Sertoli cells (pSCs) have been employed for cell therapy in pre-clinical studies for several chronic/immune diseases as they deliver molecules associated with trophic and anti-inflammatory effects. To be employed for human xenografts, pSCs products need to comply with safety and stability. To fulfill such requirements, we employed a microencapsulation technology to increase pre-transplant storage stability of specific pathogen-free pSCs (SPF-pSCs) and evaluated the in vivo long-term viability and safety of grafts.

Methods: Specific pathogen free neonatal pigs underwent testis excision under sterility. pSCs were isolated, characterized by immunofluorescence (IF) and cytofluorimetric analysis (CA) and examined in terms of viability and function [namely, production of anti-müllerian hormone (AMH), inhibin B, and transforming growth factor beta-1 (TFGβ-1)]. After microencapsulation in barium alginate microcapsules (Ba-MC), long-term SPF-pSCs (Ba-MCpSCs) viability and barium concentrations were evaluated at 1, 24 throughout 40 h to establish pre-transplant storage conditions.

Results: The purity of isolated pSCs was about 95% with negligible contaminating cells. Cultured pSCs monolayers, both prior to and after microencapsulation, maintained high function and full viability up to 24 h of storage. At 40 h post-encapsulation, pSCs viability decreased to 80%. Barium concentration in Ba-MCpSCs lagged below the normal maximum daily allowance and was stable for 4 months in mice with no evident side effects.

Conclusions: Such results suggest that this protocol for the isolation and microencapsulation of pSCs is compatible with long-haul transportation and that Ba-MCpSCs could be potentially employable for xenotransplantation.

Keywords: Sertoli cells; microcapsules; specific pathogen free; xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates
  • Animals
  • Animals, Newborn
  • Cell Separation
  • Cell Transplantation / methods
  • Cells, Cultured
  • Glucuronic Acid
  • Hexuronic Acids
  • Humans
  • Male
  • Mice
  • Sertoli Cells / cytology
  • Sertoli Cells / physiology
  • Sertoli Cells / transplantation*
  • Specific Pathogen-Free Organisms
  • Swine
  • Transplantation, Heterologous / methods*

Substances

  • Alginates
  • Hexuronic Acids
  • Glucuronic Acid