TY - JOUR
T1 - Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation
AU - Dezawa, Mari
AU - Kanno, Hiroshi
AU - Hoshino, Mikio
AU - Cho, Hirotomi
AU - Matsumoto, Naoya
AU - Itokazu, Yutaka
AU - Tajima, Nobuyoshi
AU - Yamada, Hitoshi
AU - Sawada, Hajime
AU - Ishikawa, Hiroto
AU - Mimura, Toshirou
AU - Kitada, Masaaki
AU - Suzuki, Yoshihisa
AU - Ide, Chizuka
PY - 2004/6
Y1 - 2004/6
N2 - Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.
AB - Bone marrow stromal cells (MSCs) have the capability under specific conditions of differentiating into various cell types such as osteocytes, chondrocytes, and adipocytes. Here we demonstrate a highly efficient and specific induction of cells with neuronal characteristics, without glial differentiation, from both rat and human MSCs using gene transfection with Notch intracellular domain (NICD) and subsequent treatment with bFGF, forskolin, and ciliary neurotrophic factor. MSCs expressed markers related to neural stem cells after transfection with NICD, and subsequent trophic factor administration induced neuronal cells. Some of them showed voltage-gated fast sodium and delayed rectifier potassium currents and action potentials compatible with characteristics of functional neurons. Further treatment of the induced neuronal cells with glial cell line-derived neurotrophic factor (GDNF) increased the proportion of tyrosine hydroxylase-positive and dopamine-producing cells. Transplantation of these GDNF-treated cells showed improvement in apomorphine-induced rotational behavior and adjusting step and paw-reaching tests following intrastriatal implantation in a 6-hydroxy dopamine rat model of Parkinson disease. This study shows that a population of neuronal cells can be specifically generated from MSCs and that induced cells may allow for a neuroreconstructive approach.
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U2 - 10.1172/JCI200420935
DO - 10.1172/JCI200420935
M3 - Article
C2 - 15199405
AN - SCOPUS:3042769428
SN - 0021-9738
VL - 113
SP - 1701
EP - 1710
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 12
ER -
