Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Upcoming)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Human-derived neural progenitors functionally replace astrocytes in adult mice
Hong Chen, … , Melvin Ayala, Su-Chun Zhang
Hong Chen, … , Melvin Ayala, Su-Chun Zhang
Published February 2, 2015
Citation Information: J Clin Invest. 2015;125(3):1033-1042. https://doi.org/10.1172/JCI69097.
View: Text | PDF
Technical Advance Neuroscience

Human-derived neural progenitors functionally replace astrocytes in adult mice

  • Text
  • PDF
Abstract

Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair.

Authors

Hong Chen, Kun Qian, Wei Chen, Baoyang Hu, Lisle W. Blackbourn IV, Zhongwei Du, Lixiang Ma, Huisheng Liu, Karla M. Knobel, Melvin Ayala, Su-Chun Zhang

×

Figure 1

Human cells survive and migrate in the adult spinal cord.

Options: View larger image (or click on image) Download as PowerPoint
Human cells survive and migrate in the adult spinal cord.
(A) Distributi...
(A) Distribution of hNu+ and GFP+ cells (from ESCs) in the spinal cord over time (0.5 to 9 months). (B) The dividing human cells (from iPSCs) were revealed by Ki67+/hNu+ over time. Scale bar: 50 μm. (C) Human cells (marked by GFP) in the spinal cord migrated longitudinally to both rostral (A) and caudal (P) areas, and the distance (mean ± SEM) that hNu+ cells spread in the spinal cord was measured (n = 6), with “O” indicating the injection location. (D) Quantification of Ki67+/hNu+ cells (mean ± SEM) in the spinal cord over time. Ki67 expression in the mouse spinal cord was used as an endogenous control (n = 6). (E) Longitudinal view of the distribution of hNu+ cells along the spinal cord. Scale bar: 500 μm.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts