http://nnr.sagepub.com/content/24/7/636.short
- Jin Zhong, PhD
- Albert Chan, MD
- Harley I. Kornblum, MD, PhD
- Guoping Fan, PhD
- S. Thomas Carmichael, MD, PhD
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA, scarmichael@mednet.ucla.edu
Abstract
Stroke is a leading cause of adult
disability. Stem/progenitor cell transplantation improves recovery after
stroke in rodent
models. These studies have 2 main limitations to
clinical translation. First, most of the cells in stem/progenitor
transplants
die after brain transplantation. Second,
intraparenchymal approaches target transplants to normal brain adjacent
to the stroke,
which is the site of the most extensive natural
recovery in humans. Transplantation may damage this tissue. The stroke
cavity
provides an ideal target for transplantation
because it is a compartmentalized region of necrosis, can accept a high
volume
transplant without tissue damage, and lies directly
adjacent to the most plastic brain area in stroke. However, direct
transplantation
into the stroke cavity has caused massive death in
the transplant. To overcome these limitations, the authors tested
stem/progenitor
transplants within a specific biopolymer hydrogel
matrix to create a favorable environment for transplantation into the
infarct
cavity after stroke, and they tested this in
comparison to stem cell injection without hydrogel support. A biopolymer
hydrogel
composed of cross-linked hyaluronan and heparin
sulfate significantly promoted the survival of 2 different neural
progenitor
cell lines in vitro in conditions of stress and in
vivo into the infarct cavity. Quantitative analysis of the transplant
and
surrounding tissue indicates diminished
inflammatory infiltration of the graft with the hydrogel transplant.
This result indicates
that altering the local environment in stem cell
transplantation enhances survival and diminishes cell stress. Stem cell
transplantation
into the infarct cavity within a pro-survival
hydrogel matrix may provide a translational therapy for stroke recovery.
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