Research in Neurosurgery
Brain Tumour Stem Cell
Laboratory
Daniel Weinberg
Supervisor: Dr Quiñones-Hinojosa
SBNS Elective Report
Daniel Weinberg
I spent my 8-week elective at the prestigious Johns Hopkins Hospital in
Baltimore (USA), working under the supervision of Dr Quiñones-Hinojosa
(known as “Dr Q”) in the Brain Tumour Stem Cell Laboratory. Previously, I
have investigated the use of neural stem cell therapies and magnetic
nanoparticles during my intercalated M.Phil. Hence, I was keen to further
develop my interests in cutting edge nanotechnology platforms and
neurotherapeutic agents by working with Dr Quiñones-Hinojosa in a heavily
translational environment.
Background
Glioblastoma multiforme (GBM) is the most common form of brain tumour in
adults, with over 25,000 new cases diagnosed each year in the USA alone.[1]
Patients with GBM have a poor prognosis with a median survival of 14.6
months despite combined surgical resection, radiotherapy and
chemotherapy.[1] The persistence of GBM cells following these treatments
calls for the development of novel therapies to target and destroy remaining
cancer cells.
One potential strategy currently being investigated is the use of gene therapy
to induce apoptosis in tumour cells and modulate the immune response to
GBMs. Considering the risk of insertional mutagenesis and immunogenicity
issues with virus-mediated gene therapy, Dr Q and his team are exploring the
use of nanoparticle-mediated gene delivery (transfection) to GBM cells.
Additionally, Dr Q and his team are exploiting the pathotropic capabilities of
mesenchymal stem cells (MSCs) in order to specifically target GBM cells.
Here, human adipose-derived MSCs (hAMSCs) can be engineered with
therapeutic proteins and serve as ‘Trojan horses’ to achieve localised
therapeutic effects. Importantly, hAMSCs have been shown to bypass the
blood brain barrier and migrate long distances across brain tissue.[2]
Dr Q’s end goal is to harvest, engineer and transplant autologous hAMSCs
from GBM patients, in order to destroy remaining GBM cells. In this respect,
one of three strategies could be considered: transplanting engineered
hAMSCs (i) intraoperatively following tumour resection, (ii) during follow up
surgery into the resection site, (iii) intravenously as a course of cell therapy.
The first strategy would require efficient hAMSC transfection to be achieved
within a short time period, which may not be feasible. Hence, strategy (ii) may
offer sufficient time for hAMSCs to achieve high transfection rates. Lastly, one
could consider option (iii) whereby hAMSCs could be delivered in a similar
fashion to chemotherapy resulting in sustained therapeutic benefits.
Objectives and Learning
The objectives for my elective were threefold:
1. To develop my understanding of a career in academic neurooncological surgery
2. To enhance my knowledge of the current nanotechnological advances
and strategies for treating glioblastoma patients
3. To enhance my pre-existing laboratory skills and learn new techniques
SBNS Elective Report
Daniel Weinberg
Shadowing Dr Q and his team provided me with excellent insight into the
career of an academic neurosurgeon. I was able to appreciate the importance
of narrowing the gap between laboratory research and clinical trials, having
been actively involved in a number of translational research projects at Johns
Hopkins. I have learnt about novel and evolving strategies being investigated
to treat GBM patients, including the use of stem cell, nanoparticle and
combinatory therapies, which offer hope for GBM patients to improve and
potentially cure their devastating conditions. Having thoroughly enjoyed my
involvement with in vivo studies, I have learnt a diversity of new skills
including mouse anaesthesia, stereotactic neurosurgery, euthanasia and
cryrosectioning. Further, I developed skills in deriving hAMSCs from human
fat samples and maintaining a range of primary and commercial GBM cell
lines.
This elective has been a fantastic opportunity to advance my skills with
computer software including AxioVision, ImageJ and MATLAB, which will
prove to be useful throughout the course of my Academic Foundation
Programme. Having had exposure to grant writing and being involved in
multidisciplinary research meetings, I have gained a comprehensive
understanding of a career in academic neurosurgery. I was also able to
enhance my clinical knowledge through attending weekly neurosurgery grand
rounds and shadowing Dr Q in the operating theatre.
Conclusions
Working alongside Dr Q and his team was a truly inspirational experience and
has heightened my desire to pursue a career in academic neurosurgery. I
have gained an invaluable portfolio of new laboratory and research skills
within a short time period, which I look forward to using in my future career.
The learning environment at Johns Hopkins was fantastic, and I would highly
recommend an elective here to anyone considering a career in neurosurgery.
Acknowledgements
I would like to thank Dr Quiñones-Hinojosa and his team for this fantastic
opportunity and their support. Further, I owe my thanks to the Society of
British Neurological Surgeons for their most generous financial support, which
without, this opportunity would not have been possible.
References
1. Guerrero-Cázares H, Tzeng SY, Young NP, Abutaleb AO, Quiñones-Hinojosa A, Green
JJ. Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA
delivery to human glioblastoma in vitro and in vivo. ACS Nano. 2014;8(5):5141-53.
2. Li Q, Wijesekera O, Salas SJ, Wang JY, Zhu M, Aprhys C, Chaichana KL, Chesler DA,
Zhang H, Smith CL, Guerrero-Cázares H, Levchenko A, Quiñones-Hinojosa A.
Mesenchymal Stem Cells from Human Fat Engineered to Secrete BMP4 Are
Nononcogenic, Suppress Brain Cancer, and Prolong Survival. Clin Cancer Res.
2014;20(9):2375-87.