Effects Of Human Umbilical Cord Blood Research Articles

Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder.

Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 106) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy.

Nerve Growth Factor and Human Umbilical Cord Blood-Derived Cells Confer Neurovascular Protection in Ischemia

Human umbilical cord blood (HUCB), a valuable source for cell therapy of hematologic diseases, was recently found to confer neuroprotection in animal models of brain injury. To explore the neuroprotective properties of HUCB in an ischemic environment, we studied a unique sub-population of collagen-adherent cells. In the presence of nerve growth factor (NGF) and interferon-gamma, these cells differentiate in vitro into a neuronal phenotype (termed HUCBNPs). Using a closed-head injury brain trauma model, we recently demonstrated neuroprotective effects of HUCB upon their local injection into the brain. Our in-vitro studies indicated that upon co-culture with ischemia exposed PC12 cells, HUCBNP conferred about 30% neuroprotection, as assessed by decreased lactate dehydrogenase (LDH) release and inhibition of caspase-3 activity. HUCBNP decreased by 95% the level of free radicals in the insulted-PC12 cells, which was in correlation with the appearance of antioxidants and NGF in the medium. HUCBNP-induced neuroprotection also correlated with changes in NGF mRNA expression levels, a process which was blocked by K252a, an antagonist of the NGF-neurotrophin receptor TrkA. To further extend the possible contribution of NGF-mediated protective role, we investigated its neuroprotective mechanisms using PC12 cells and brain capillary endothelial cells exposed to ischemic insult. Pretreatment of the cultures with NGF conferred neuroprotection in a dose- and time-dependent fashion. Time course experiments indicated marked activation of mitogen activated protein kinasas (MAPKs) during the ischemic insult, while treatment of the cultures with NGF inhibited them to different degrees. It appears that both neuronal and endothelial compartments may be protected by NGF under ischemic conditions. Therefore, in future neuroprotection studies, we propose to address additional components of the neurovascular unit such as astrocytes and pericytes in mono-, co- and multi-culture setups. In conclusion, our findings indicate that HUCBNP-induced neuroprotection involves antioxidant(s) and NGF, which by paracrine and/or autocrine route, affects all components of the neurovascular unit.