Experimental programs carried out to date cover:
�� Optimum media selection – Many mixtures and substances were
examined to determine which of them yields the best results on a
repetitive basis for mesenchymal cell propagation and differentiation
into dopamine and GDNF- producing cells.
�� Cell characterization – Studies were conducted to evaluate the
induction of neuronal and astrocyte-like cells by following the typical
structure and surface markers.
�� Cell physiology – Dopamine and GDNF production and release from
the induced cells were assayed and measured.
�� Genetic biochemistry – Studies showing the induction of specific
genes, which are expressed in neurons and astrocytes, were
conducted.
�� Cell electro-physiology – A complex, computerized measurement
system was used to evaluate the typical electrical potential of
neurons in the induced cells.
�� Animal studies – The induced BMSc was transplanted into the
various area of the brain of an animal model of PD in which
dopaminergic cells were lost. The survival and function of the cells
were observed. They continued to express neuronal function,
including the ability to recover. An animal model of ALS in transgenic
mice harboring the human mutation for super oxide dismutase
(mSOD1) was also used. In these models, the onset of the disease
and motor function were observed.
�� Imaging Studies – Imaging studies were conducted to evaluate the
survival of the transplanted cells and follow the location and
immigration of the cells into different brain and spinal cord areas.
Summary of PreClinical Data Showing Efficacy
|
Study |
End Points |
Outcome |
Reference |
|
Induction of neuron-like cells from mouse bone marrow
|
•Morphology
•Neuronal Markers
|
Expression of neuronal
proteins
|
Levy, et al. J Mol. Neurosci.,
2003
|
|
Induction of dopaminergic-like
cells from human bone marrow |
•Morphology
•Neuronal Markers
•Dopamine
secretion
|
•Neuronal morphology
•Expression of neuronal proteins
•Expression of dopaminergic markers
•Secretion of dopamine
|
•Blondheim, et al. Stem Cells and Development, 2006
•Barzilai, et al. IMAJ,2005
•Levy, et al. J Mol. Neurosci., 2004
•Offen, et al. Stem cell & gene-based therapy: Frontiers in
Regenerative Medicine, 2005 |
|
Induction of astrocyte-like cells
from human bone marrow
|
•Morphology
•Astrocyte markers
•Secretion of
neurotrophic
factors
•Astrocyte
functions |
•Astrocyte morphology
•High levels of
neurotrophic factors
(GDNF,NGF)
•Glutamate uptake |
ISSCR, 2006
|
|
Transplantation of dopaminergic
cells from mouse bone marrow
to lesioned mice (PD model) |
•Survival
•Migration
|
•Transplanted cells survived for 3 months
•The cells migrated to the
lesioned sites
|
Hellmann, et al. Neurosci. Lett., 2005
|
|
Transplantation of dopamine-like
cells from mouse bone marrow
to lesioned mice (PD model)
|
•Rotational
behavior
•Cell survival
•Histology
|
•Improvement in the rotation behavior (65%)
•Cells survived for 4 months
•Cells expressed
dopaminergic markers
|
Presented at the Internl. Society for Stem Cell Research (ISSRC) 2005
|
|
Transplantation of dopamine-like
cells from human bone marrow
to lesioned rats (PD model)
|
•Rotational
behavior
•Cell survival
•Histology
|
•Improvement in the rotation behavior (50%)
•Cells survived for 4 months
•Cells expressed
dopaminergic markers
|
Presented at ISSRC 2006
|
|
Transplantation of astrocyte-like
cells from human bone marrow
to lesioned rats (PD model)
|
•Rotational
behavior
•Rotorod
•Sunflower eating test
•Histology
|
Improvement in the motor behavior (60%)
•Cells survived for 3 months
•Cells expressed
astrocyte markers
|
Presented at ISSRC 2006
|
Overview
