Behavior of xeno-Transplanted undifferentiated human induced pluripotent stem cells is impacted by microenvironment without evidence of tumors

Veronica Martinez-Cerdeno, Bonnie L. Barrilleaux, Ashley McDonough, Jeanelle Ariza, Benjamin T.K. Yuen, Priyanka Somanath, Catherine T. Le, Craig Steward, Kayla Horton-Sparks, Paul S Knoepfler

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Human pluripotent stem cells (hPSC) have great clinical potential through the use of their differentiated progeny, a population in which there is some concern over risks of tumorigenicity or other unwanted cellular behavior due to residual hPSC. Preclinical studies using human stem cells are most often performed within a xenotransplant context. In this study, we sought to measure how undifferentiated hPSC behave following xenotransplant. We directly transplanted undifferentiated human induced pluripotent stem cells (hIPSC) and human embryonic stem cells (hESC) into the adult mouse brain ventricle and analyzed their fates. No tumors or precancerous lesions were present at more than one year after transplantation. This result differed with the tumorigenic capacity we observed after allotransplantation of mouse ESC into the mouse brain. A substantial population of cellular derivatives of undifferentiated hESC and hIPSC engrafted, survived, and migrated within the mouse brain parenchyma. Within brain structures, transplanted cell distribution followed a very specific pattern, suggesting the existence of distinct microenvironments that offer different degrees of permissibility for engraftment. Most of the transplanted hESC and hIPSC that developed into brain cells were NeuN+ neuronal cells, and no astrocytes were detected. Substantial cell and nuclear fusion occurred between host and transplanted cells, a phenomenon influenced by microenvironment. Overall, hIPSC appear to be largely functionally equivalent to hESC in vivo. Altogether, these data bring new insights into the behavior of stem cells without prior differentiation following xenotransplantation into the adult brain.

Original languageEnglish (US)
Pages (from-to)1409-1423
Number of pages15
JournalStem Cells and Development
Volume26
Issue number19
DOIs
StatePublished - Oct 1 2017

Fingerprint

Induced Pluripotent Stem Cells
Pluripotent Stem Cells
Brain
Neoplasms
Nuclear Fusion
Stem Cells
Heterologous Transplantation
Cell Fusion
Astrocytes
Population
Transplantation
Human Embryonic Stem Cells

Keywords

  • Cell fate
  • Microenvironment
  • Teratoma
  • Tumorigenesis

ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Behavior of xeno-Transplanted undifferentiated human induced pluripotent stem cells is impacted by microenvironment without evidence of tumors. / Martinez-Cerdeno, Veronica; Barrilleaux, Bonnie L.; McDonough, Ashley; Ariza, Jeanelle; Yuen, Benjamin T.K.; Somanath, Priyanka; Le, Catherine T.; Steward, Craig; Horton-Sparks, Kayla; Knoepfler, Paul S.

In: Stem Cells and Development, Vol. 26, No. 19, 01.10.2017, p. 1409-1423.

Research output: Contribution to journalArticle

Martinez-Cerdeno, Veronica ; Barrilleaux, Bonnie L. ; McDonough, Ashley ; Ariza, Jeanelle ; Yuen, Benjamin T.K. ; Somanath, Priyanka ; Le, Catherine T. ; Steward, Craig ; Horton-Sparks, Kayla ; Knoepfler, Paul S. / Behavior of xeno-Transplanted undifferentiated human induced pluripotent stem cells is impacted by microenvironment without evidence of tumors. In: Stem Cells and Development. 2017 ; Vol. 26, No. 19. pp. 1409-1423.
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