Advances in preclinical hematopoietic stem cell models and possible implications for improving therapeutic transplantation

Ellen Fraint, Bianca A. Ulloa, María Feliz Norberto, Kathryn S. Potts, Teresa V. Bowman

Research output: Contribution to journalReview articlepeer-review

Abstract

Hematopoietic stem cell transplantation (HSCT) is a treatment for many malignant, congenital, and acquired hematologic diseases. Some outstanding challenges in the HSCT field include the paucity of immunologically-matched donors, our inability to effectively expand hematopoeitic stem cells (HSCs) ex vivo, and the high infection risk during engraftment. Scientists are striving to develop protocols to generate, expand and maintain HSCs ex vivo, however these are not yet ready for clinical application. Given these problems, advancing our understanding of HSC specification, regulation and differentiation in preclinical models is essential to improve the therapeutic utility of HSCT. In this review, we link biomedical researchers and transplantation clinicians by discussing the potential therapeutic implications of recent fundamental HSC research in model organisms. We consider deficiencies in current HSCT practice, such as problems achieving adequate cell dose for successful and rapid engraftment, immense inflammatory cascade activation after myeloablation, and graft-vs-host disease. Furthermore, we discuss recent advances in the field of HSC biology and transplantation made in preclinical models of zebrafish, mouse and nonhuman primates that could inform emerging practice for clinical application.

Original languageEnglish (US)
JournalStem Cells Translational Medicine
DOIs
StateAccepted/In press - 2020

Keywords

  • graft-vs-host disease
  • hematopoietic stem cells
  • lineage tracing
  • preclinical models
  • transplantation

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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