2 research outputs found
Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma
Transdifferentiation (TD) is a recent advancement in somatic cell reprogramming. The direct conversion of TD eliminates the pluripotent intermediate state to create cells that are ideal for personalized cell therapy. Here we provide evidence that TD-derived induced neural stem cells (iNSCs) are an efficacious therapeutic strategy for brain cancer. We find that iNSCs genetically engineered with optical reporters and tumouricidal gene products retain the capacity to differentiate and induced apoptosis in co-cultured human glioblastoma cells. Time-lapse imaging shows that iNSCs are tumouritropic, homing rapidly to co-cultured glioblastoma cells and migrating extensively to distant tumour foci in the murine brain. Multimodality imaging reveals that iNSC delivery of the anticancer molecule TRAIL decreases the growth of established solid and diffuse patient-derived orthotopic glioblastoma xenografts 230- and 20-fold, respectively, while significantly prolonging the median mouse survival. These findings establish a strategy for creating autologous cell-based therapies to treat patients with aggressive forms of brain cancer
Relationship of oxidative stress and antioxidant response with vaso-occlusive crisis in sickle cell anaemia
Background: Though sickle cell anaemia (SCA) is known to promote
oxidative stress, there is paucity of information on the relationship
between oxidative stress and vaso-occlusive crisis (VOC). Objective:
This study was undertaken to evaluate the relationship of oxidative
stress and antioxidant response with VOC in SCA. Methods: A
cross-sectional case-control study was carried out at University of
Nigeria Teaching Hospital (UNTH), Ituku-Ozalla, Enugu Nigeria involving
116 individuals which included 36 SCA subject, 40 sickle cell carriers
(AS) and 40 healthy individuals (AA). Baseline information as well as
the frequency of VOC was obtained from the participants and anaemia as
well as oxidative stress and antioxidant indices were assessed in
blood. Results: Anaemia was prevalent (88.9 %) in SCA individuals
compared to AS (52.5%) and AA (47.5 %) individuals. Nitric oxide
scavenging (NOS) and superoxide dismutase (SOD) activities as well as
glutathione level were significantly (p<0.005) lower while catalase
activity was higher in SCA individuals compared to controls (AA and
AS). Higher malondialdehyde (MDA) level was associated with very severe
VOC while low level of NOS activity was associated with severe VOC in
SCA individuals. Conclusion: Sickle cell anaemia exhibited oxidative
stress and alteration in the levels of antioxidant indices which was
possibly associated with vaso-occlusive crisis