Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like cells in vitro.
Abstract
A large percentage of the population may be expected to experience painful symptoms
or disability associated with intervertebral disc (IVD) degeneration - a condition
characterized by diminished integrity of tissue components. Great interest exists
in the use of autologous or allogeneic cells delivered to the degenerated IVD to promote
matrix regeneration. Induced pluripotent stem cells (iPSCs), derived from a patient's
own somatic cells, have demonstrated their capacity to differentiate into various
cell types although their potential to differentiate into an IVD cell has not yet
been demonstrated. The overall objective of this study was to assess the possibility
of generating iPSC-derived nucleus pulposus (NP) cells in a mouse model, a cell population
that is entirely derived from notochord. This study employed magnetic activated cell
sorting (MACS) to isolate a CD24(+) iPSC subpopulation. Notochordal cell-related gene
expression was analyzed in this CD24(+) cell fraction via real time RT-PCR. CD24(+)
iPSCs were then cultured in a laminin-rich culture system for up to 28 days, and the
mouse NP phenotype was assessed by immunostaining. This study also focused on producing
a more conducive environment for NP differentiation of mouse iPSCs with addition of
low oxygen tension and notochordal cell conditioned medium (NCCM) to the culture platform.
iPSCs were evaluated for an ability to adopt an NP-like phenotype through a combination
of immunostaining and biochemical assays. Results demonstrated that a CD24(+) fraction
of mouse iPSCs could be retrieved and differentiated into a population that could
synthesize matrix components similar to that in native NP. Likewise, the addition
of a hypoxic environment and NCCM induced a similar phenotypic result. In conclusion,
this study suggests that mouse iPSCs have the potential to differentiate into NP-like
cells and suggests the possibility that they may be used as a novel cell source for
cellular therapy in the IVD.
Type
Journal articleSubject
AnimalsAntigens, CD24
Cell Differentiation
Culture Media, Conditioned
Induced Pluripotent Stem Cells
Intervertebral Disc Degeneration
Mice
Notochord
Phenotype
Permalink
https://hdl.handle.net/10161/8878Published Version (Please cite this version)
10.1371/journal.pone.0075548Publication Info
Chen, Jun; Lee, Esther J; Jing, Liufang; Christoforou, Nicolas; Leong, Kam W; & Setton,
Lori A (2013). Differentiation of mouse induced pluripotent stem cells (iPSCs) into nucleus pulposus-like
cells in vitro. PLoS One, 8(9). pp. e75548. 10.1371/journal.pone.0075548. Retrieved from https://hdl.handle.net/10161/8878.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Jun Chen
Associate Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Kam Leong
Adjunct Professor of Biomedical Engineering
Professor Leong's research interest focuses on biomaterials design, particularly on
synthesis of nanoparticles for DNA-based therapeutics, and nanostructured biomaterials
for regenerative medicine
Biomaterials Design:
design of self-assembled fibers for tissue engineering
microfluidics-mediated synthesis of multifunctional nanoparticles for drug and gene
delivery
synthesis of novel quantum dots for biomedical applications
Con
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
Lori A. Setton
Adjunct Professor of Biomedical Engineering
Research in Setton's laboratory is focused on the role of mechanical factors in the
degeneration and repair of soft tissues of the musculoskeletal system, including the
intervertebral disc, articular cartilage and meniscus. Work in the Laboratory is focused
on engineering and evaluating materials for tissue regeneration and drug delivery.
Studies combining engineering and biology are also used to determine the role of mechanical
factors to promote and control healing of cartilaginous tissues. Re
Alphabetical list of authors with Scholars@Duke profiles.

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info