Immunohistochemical toolkit for tracking and quantifying xenotransplanted human stem cells

Regen Med. 2014;9(4):437-52. doi: 10.2217/rme.14.26.

Abstract

Aim: Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting.

Materials & methods: Using immunohistochemistry and in situ hybridization, we analyzed the expression of three human-specific biomarkers: Ku80, human mitochondria (hMito) and Alu.

Results: We showed that Ku80, hMito and Alu biomarkers are broadly expressed in human tissues with no or low cross-reactivity toward rat, mouse or pig tissues. In vitro, we demonstrated that their expression is stable over time and does not change along the differentiation of human-derived induced pluripotent stem cells or human glial-restricted precursors. We tracked in vivo these cell populations after transplantation in rodent spinal cords using aforementioned biomarkers and human-specific antibodies detecting apoptotic, proliferating or neural-committed cells.

Conclusion: This study assesses the human-species specificity of Ku80, hMito and Alu, and proposes useful biomarkers for characterizing human stem cells in xenotransplantation paradigms.

Keywords: cell therapy; human-specific biomarker; image quantification; stem cells; xenotransplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism*
  • Cell Tracking / methods*
  • Heterografts
  • Humans
  • Immunohistochemistry / methods
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Induced Pluripotent Stem Cells* / transplantation
  • Male
  • Mice
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation*

Substances

  • Antigens, Differentiation