Long-Term Hematopoietic Engraftment of Congenic Amniotic Fluid Stem Cells after in Utero Intraperitoneal Transplantation to Immune Competent Mice

Panicos Shangaris, Stavros P. Loukogeorgakis, Michael P. Blundell, Eleni Petra, Steven W. Shaw, Durrgah L. Ramachandra, Panagiotis Maghsoudlou, Luca Urbani, Adrian J. Thrasher, Paolo De Coppi, Anna L. David*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)
93 Downloads (Pure)

Abstract

Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13.5). At 4 and 16 weeks of age, multilineage donor engraftment was higher in congenic versus allogeneic animals. In vitro mixed lymphocyte reaction confirmed an immune response in the allogeneic group with higher CD4 and CD8 cell counts and increased proliferation of stimulated lymphocytes. IUT with congenic cells resulted in 100% of donor animals having chimerism of around 8% and successful hematopoietic long-term engraftment in immune-competent mice when compared with IUT with allogeneic cells. AFSCs may be useful for autologous cell/gene therapy approaches in fetuses diagnosed with congenital hematopoietic disorders.

Original languageEnglish
Pages (from-to)515-523
Number of pages9
JournalSTEM CELLS AND DEVELOPMENT
Volume27
Issue number8
Early online date27 Mar 2018
DOIs
Publication statusPublished - 15 Apr 2018

Keywords

  • amniotic fluid stem cells
  • in utero stem cell transplantation
  • prenatal therapy

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