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Kim JY et al. Therapeutic effects of hUCB-MSCs

with control. Although this glioma tropism has been dem- tory inhibitory factor and TNF-α. Furthermore, collagen
onstrated, the exact molecular mechanism has not been level was decreased due to up-regulation of matrix metal-
elucidated. As glioma over expressed interleukin-8 (IL-8), loproteinase-2 and reduced endogenous inhibitors, tissue
our group tested IL-8 action in hUCB-MSCs migration inhibitors of matrix metalloproteinases. These results
toward glioma. Interestingly, a high level of IL-8 was suggested that uMSCs participate in anti-fibrosis in lung
detected in the conditioned media of co-cultured glioma injury. Interestingly, hUCB-MSCs transplantation can atten-
cells with hUCB-MSCs. Recombinant IL-8 treatment of uate hyperoxia-induced lung injury in immunocompetent
[32]
hUCB-MSCs enhanced migration to the lower chamber newborn rats . A single dose of PKH26 labeled hUCB-
6
under the Transwell system. This effect was reduced by MSCs was administered intratracheally (2 × 10 cells) at
pre-treatment of hUCB-MSCs with antibody against postnatal day 5. Two abilities of hUCB-MSCs, immune
CXC chemokine receptor 1 (CXCR1) and CXCR2, IL-8 modulation and differentiation potential, were evaluated
receptor. Therefore, IL-8 will be an attracting factor for after hUCB-MSCs administration. The hyperoxia-induced
[27]
hUCB-MSCs migration toward glioma . We expect increase in the number of dead cells, myeloperoxidase ac-
that IL-8 receptor over expression in hUCB-MSCs will tivity, abnormal alveolarization and level of IL-6 mRNA
efficiently deliver cancer drugs to glioma. For application were significantly decreased with intratracheal hUCB-
of hUCB-MSCs in human glioma, more efficient and safe MSCs administration. Furthermore, increased level of
methods of therapeutic gene expression in hUCB-MSCs TNF-α, TGF-β mRNA, α-SMA protein and collagen
should be established. were significantly reduced by hUCB-MSCs. As pKH26-
labeled differentiated lung epithelial cells were observed in
hUCB-MSCs for ischemic brain damage damaged lung, collectively, hUCB-MSCs could be used for
Because brain injury due to ischemia cannot be recovered cell therapy via both anti-inflammation and regeneration in
and can result in severe functional defects in the brain, hypoxia induced lung injury.
stroke is a primary disease target for stem cell therapy. In
ischemia studies, most data show that cell therapy is per- hUCB-MSCs for liver diseases
formed using hUCB. The first evidence of a therapeutic Cirrhosis is a consequence of chronic hepatic injury char-
effect of hUCB came from Chopp’s laboratory, where rat acterized by replacement of liver tissue by fibrosis and scar
was used for middle cerebral artery occlusion to induce tissue. Cirrhosis is most commonly caused by alcoholism,
focal ischemia. Intravenous administration of hUCB re- fatty liver and hepatitis B and C. No effective therapy is
[28]
duces behavioral deficits after stroke in rats . Recently, currently available for this disease . Recent reports have
[33]
infarct volume was reduced 1 d after intra arterial delivery shown that MSCs have the capacity for differentiation
of hUCB-MSCs in canine cerebral ischemia whereas into hepatocytes. In carbon tetrachloride (CCl4)-induced
infarct volume was increased in the control groups. Trans- cirrhosis in a rat model, hUCB-MSCs infusion showed
planted hUCB-MSCs were differentiated into neurons inhibition of TGF-β1, collagen type Ⅰ and α-SMA ex-
and astrocytes in and around endothelial cells and secreted pression. In addition, CM-DiI-labeled hUCB-MSCs ex-
brain-derived neurotrophic factor and vascular endothelial pressed hepatocyte-specific markers, human albumin and
[29]
[30]
growth factor at 4 wk after transplantation . Jeong et al α-fetoprotein in injured liver . Similar data was observed
[34]
reported that transplantation of hUCB-MSCs into contra- by Yan et al . Interestingly, terminal deoxynucleotidyl
[35]
lateral regions of injured rat brain at 7 d after injury resulted transferase-mediated deoxyuridine triphosphate (dUTP)-
in significant behavioral improvement. In addition, PKH26- biotin nick end labeling and proliferating cell nuclear anti-
labled hUCB-MSCs differentiated into neural cells at the gen staining showed that transplanted hUCB-MSCs could
injured site at 4 wk after transplantation. These results prevent hepatocyte cell death and stimulate proliferation.
suggested that transplantation of hUCB-MSCs could be According to these data, hUCB-MSCs could be useful in
used in clinical trials for ischemia. Despite these interesting liver therapy. Liver contains endogenous abundant pro-
data, stem cell therapy using hUCB-MSCs have to make genitor cells for recovery of liver damage. Therefore, it
critical decisions with regard to the route of transplantation, is currently difficult to determine which stem/progenitor
type of injected cell (hUCB vs hUCB-MSCs) and timing of cell populations are best for liver disease therapy.
transplantation.

hUCB-MSCs for lung diseases CONCLUSION
Progression of acute respiratory distress syndrome is In the effort to overcome incurable disease, stem cell
demonstrated by loss of lung tissue as a result of inflam- therapy has been regarded as the next solution. In par-
mation and fibrosis. Human umbilical cord cells derived ticular, adult stem cells such as hUCB-MSCs have shown
from Wharton’s jelly with a phenotype consistent with therapeutic efficacy in various animal disease models. Com-
that of MSCs (uMSCs) were treated using a bleomycin pared to embryonic stem cells, adult stem cells have several
[31]
induced-lung injury mouse model . After 2 wk, systemic advantages for use in stem cell therapy. Adult stem cells
administration of uMSCs was located in the area of are relatively free of ethical issues, immune rejection and
inflammation and fibrosis. Injected uMSCs reduced inflam- tumor formation. In particular, hUCB-MSCs are obtained
mation and inhibited expression of TGF-β, IFN-γ and from discarded umbilical cord blood after child birth. If
proinflammatory cytokines, including macrophage migra- informed consent is available from pregnant mothers,

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