3 research outputs found
An Injectable Decellularized Matrix That Improves Mesenchymal Stem Cell Engraftment for Therapeutic Angiogenesis
Stem cell therapy
has great potential for the treatment of ischemic
diseases, but poor engraftment of implanted stem cells limits the
therapeutic efficacy. Here, we developed an approximately 80 Ī¼m
injectable decellularized matrix (IDM) to increase the angiogenic
efficacy of mesenchymal stem cells by improving the engraftment of
the stem cells implanted in to an ischemic tissue. Adhesion of human
adipose tissue-derived stem cells (hADSCs) to the IDM enhanced the
cell viability and upregulated angiogenic factors in vitro under either
cell adhesion-suppressive conditions or hypoxic conditions, which
simulated the microenvironment of ischemic tissues. In a murine ischemic-hindlimb
model, hADSCs that were attached to the IDM and subsequently injected
into an ischemic region showed better grafting and angiogenic factor
expression. The hADSCāIDM implantation subsequently promoted
the formation of microvessels, attenuated fibrosis, and increased
blood perfusion in the ischemic region, as compared to implantation
of hADSCs only. The IDM may be an effective off-the-shelf material
that can enhance therapeutic efficacy of stem cell therapy for ischemic
diseases
Therapeutic Efficacy-Potentiated and Diseased Organ-Targeting Nanovesicles Derived from Mesenchymal Stem Cells for Spinal Cord Injury Treatment
Human
mesenchymal stem cell (hMSC)-derived exosomes have been spotlighted
as a promising therapeutic agent for cell-free regenerative medicine.
However, poor organ-targeting ability and insufficient therapeutic
efficacy of systemically injected hMSC-exosomes were identified as
critical limitations for their further applications. Therefore, in
this study we fabricated iron oxide nanoparticle (IONP)āincorporated
exosome-mimetic nanovesicles (NV-IONP) from IONP-treated hMSCs and
evaluated their therapeutic efficacy in a clinically relevant model
for spinal cord injury. Compared to exosome-mimetic nanovesicles (NV)
prepared from untreated hMSCs, NV-IONP not only contained IONPs which
act as a magnet-guided navigation tool but also carried greater amounts
of therapeutic growth factors that can be delivered to the target
cells. The increased amounts of therapeutic growth factors inside
NV-IONP were attributed to IONPs that are slowly ionized to iron ions
which activate the JNK and c-Jun signaling cascades in hMSCs. In vivo
systemic injection of NV-IONP with magnetic guidance significantly
increased the amount of NV-IONP accumulating in the injured spinal
cord. Accumulated NV-IONP enhanced blood vessel formation, attenuated
inflammation and apoptosis in the injured spinal cord, and consequently
improved spinal cord function. Taken together, these findings highlight
the development of therapeutic efficacy-potentiated extracellular
nanovesicles and demonstrate their feasibility for repairing injured
spinal cord
Dual Roles of Graphene Oxide To Attenuate Inflammation and Elicit Timely Polarization of Macrophage Phenotypes for Cardiac Repair
Development of localized
inflammatory environments by M1 macrophages
in the cardiac infarction region exacerbates heart failure after myocardial
infarction (MI). Therefore, the regulation of inflammation by M1 macrophages
and their timely polarization toward regenerative M2 macrophages suggest
an immunotherapy. Particularly, controlling cellular generation of
reactive oxygen species (ROS), which cause M1 differentiation, and
developing M2 macrophage phenotypes in macrophages propose a therapeutic
approach. Previously, stem or dendritic cells were used in MI for
their anti-inflammatory and cardioprotective potentials and showed
inflammation modulation and M2 macrophage progression for cardiac
repair. However, cell-based therapeutics are limited due to invasive
cell isolation, time-consuming cell expansion, labor-intensive and
costly <i>ex vivo</i> cell manipulation, and low grafting
efficiency. Here, we report that graphene oxide (GO) can serve as
an antioxidant and attenuate inflammation and inflammatory polarization
of macrophages <i>via</i> reduction in intracellular ROS.
In addition, GO functions as a carrier for interleukin-4 plasmid DNA
(IL-4 pDNA) that propagates M2 macrophages. We synthesized a macrophage-targeting/polarizing
GO complex (MGC) and demonstrated that MGC decreased ROS in immune-stimulated
macrophages. Furthermore, DNA-functionalized MGC (MGC/IL-4 pDNA) polarized
M1 to M2 macrophages and enhanced the secretion of cardiac repair-favorable
cytokines. Accordingly, injection of MGC/IL-4 pDNA into mouse MI models
attenuated inflammation, elicited early polarization toward M2 macrophages,
mitigated fibrosis, and improved heart function. Taken together, the
present study highlights a biological application of GO in timely
modulation of the immune environment in MI for cardiac repair. Current
therapy using off-the-shelf material GO may overcome the shortcomings
of cell therapies for MI