J.Blanco (e-mail: jblancof@csic-iccc.santpau.es)
Research Topics: The group has developed photonic non invasive imaging procedures to monitor and quantify
the distribution of small populations of cells, tumour metastasis and stem cells, in small animal models. The group is
interested in developing further the imaging technology, including the development of viral vectors with multiple
promoters to regulate luciferase gene expression and allow imaging of changes in gene expression.
Non-Invasive Imaging: The strategy is based on a) the use of viral vectors to tag the cells of interest with
luciferase genes, as very sensitive cell lineage reporters; b) implantation of luciferase expressing cells in live animals
(generally nude mice); c) tracking and quantification of luciferase expressing cells by in vivo non-invasive imaging
using a high sensitivity video systems. Images of luciferase activity contain relevant information on the organ
distribution and number of cells in the mouse body. Use of tissue specific promoters allows non invasive monitoring
of cell differentiation.
Oncology: We are interested in the study of tumour proliferation and metastatic spread and
have developed tumour metastasis models based on bioluminiscence technology. Such
procedures allow the repeated evaluation of tumour cell burden and distribution, without the
need to sacrifice large numbers of experimental animals and generating better reproducibility
and consistency of the data. Additionally, ex vivo luminometric analysis of luciferase activity in
homogenates of target organs provides alternative and sensitive estimates of tumour cell
number, allowing detection and independent validation of the in vivo generated data. The
system is very sensitive and easy to use, allowing the detection of as few as 5 to 10 metastatic
cells in a mouse lymph node and approximately 100 cells in larger organs, like the liver.
The figure shows a nude mice bearing a 16 week old human PC-3.Sluc solid prostate tumor implanted
orthotopically and lymph node metastasis (ventral view).
Tumour therapy: We are currently applying photonic non invasive imaging to
explore the use of mesenchymal stem cells as vehicles for tumour therapy. Non
invasive imaging allows monitoring of cell homing and tumour cell killing. The
image shows stem cells at tumor sites 7 weeks post implantation in the same
mouse. Left panel: human prostate PC-3 tumors expressing renilla luciferase.
Right panel: human mesenchymal stem cells expressing firefly luciferase.
Stem cells for tissue repair: We are currently using non invasive imaging technology to explore the use of
mesenchymal
stem
cells
in
tissue
regeneration.
This
convenient approach
allows monitoring of
stem cell proliferation
/differentiation
in
vivo, as well as
evaluating the performance of “stem cell/scaffold” combinations for tissue regeneration.
The images show the same nude mouse bearing a calvaria implant of hydrogel scaffolds seeded with
mesenchymal stem cells expressing firefly luciferase. Light intensity (blue low; red, high) indicates number of
cells. Imaging times, post implantation, are indicated on top.
References:
- N. Rubio, M. Martínez-Villacampa and J. Blanco Traffic to lymph nodes of PC-3 prostate tumour cells in nude
mice visualized using the luciferase gene as a tumour cell marker. Lab. Invest., 78:1315-1325 (1998)
- N. Rubio, M. Martínez-Villacampa, N. El Hilali and J. Blanco Metastatic burden in nude mice organs measured
using prostate tumour PC-3 cells expressing the luciferase gene as a quantifiable tumour cell marker. Prostate,
44:133-143 (2000)
- N. El Hilali, N. Rubio, M. Martínez-Villacampa and J. Blanco Combined non-invasive imaging and
luminometric quantification of luciferase labelled human prostate tumours and metastases. Lab Invest., 82:1563-1571
(2002)
- L. España, Y. Fernández, N. Rubio, A. Torregrosa, J. Blanco and A. Sierra Overexpression of Bcl-XL in human
breast cancer cells enhanced organ-selective lymph node metastasis. Breast Cancer Res., 87:33-44 (2004)
- N. ElHilali, N. Rubio and J. Blanco Whole body luminometric monitoring of luciferase labelled human tumours
growing in nude mice., Eur. J. Cancer., 40: 2851-2858 (2004)
- N. El Hilali, N. Rubio and J. Blanco Different effect of Paclitaxel on primary tumour mass, tumour cell contents
and metastases for four experimental human prostate tumours expressing luciferase., Clinical Cancer Res., 11:12531258 (2005)
- J.R. Pineda, N. Rubio, P. Akerud, N. Urban, L. Badimón, E. Arenas, J. Alberch, J. Blanco and J.M. Canals
Neuroprotection by GDNF-secreting stem cells in a Huntington´s disease model: Non invasive optical neuroimaging
of brain implanted cells. Gene Therapy (2006) [Epub ahead of print] doi:10.1038]
- I. Román, M. Vilalta, J. Rodriguez, A.M. Matthies, S. Srouji J. Hubell. E. Livne, N. Rubio and J. Blanco
Analysis of stem cell-scaffold combinations by in vivo non-invasive photonic imaging. Submitted to Biomaterials
(2006)
J.Blanco: Cardiovascular Research Center CSIC-ICCC; Hospital de la Santa Creu i Sant Pau Av. S. Antoni M.
Claret, 167 08025 Barcelona (Spain) ;Tef. 34-93-556 5905; e-mail:jblancof@csic-iccc.santpau.es