TY - JOUR
T1 - Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons
AU - Tatard, Valerie M.
AU - D'Ippolito, Gianluca
AU - Diabira, Sylma
AU - Valeyev, Alexander
AU - Hackman, John
AU - McCarthy, Micheline
AU - Bouckenooghe, Thomas
AU - Menei, Philippe
AU - Montero-Menei, Claudia N.
AU - Schiller, Paul C.
N1 - Funding Information:
This work was in part supported by the Department of Veterans Affairs and the ‘Fondation de la Recherché Medicale.’ The authors are grateful to Drs. Guy Howard and Carlos Perez-Stable for rewarding discussions and critical review of the manuscript; Drs. Camillo Ricordi and Antonello Pileggi and Ms. Julie Allickson from the Diabetes Research Institute (University of Miami School of Medicine) for providing the whole bone marrow; David Vazquez, Irvin Vidaurre and Blanca Rodriguez for expert technical assistance in cell culture and cell assays; and Virginia Roos for help in preparing the manuscript.
PY - 2007/2
Y1 - 2007/2
N2 - Marrow-isolated adult multilineage inducible (MIAMI) cells were differentiated in vitro to neuronal cells in a neurotrophin-dependent fashion. After induction, the cells revealed electrophysiological features similar to those observed in mature neurons. Primary early passage human MIAMI cells without any type of co-cultures with other cell types were used. The developmental program involved a multi-step process requiring the concerted action of brain-derived neurotrophic factor, nerve growth factor and depended on neurotrophin-3, after basic fibroblast growth factor withdrawal. MIAMI-derived neuron-like cells sequentially expressed the neuronal markers, developed a complex neurite outgrowth and arborization, and acquired electrophysiological characteristics similar to those observed in mature neurons. The young and old MIAMI-derived neuronal cells developed both inward and outward currents upon depolarization, similar to those observed in normal neurons. These results represent the earliest evidence that neurotrophin-3 can direct the differentiation of non-neural stem cells from human adult bone marrow stroma to neuron-like cells in vitro. Supplementing the aforementioned multi-step process with sonic hedgehog, fibroblast growth factor 8, and retinoic acid increased the expression of molecules involved in dopaminergic differentiation and of tyrosine hydroxylase, the rate limiting enzyme of dopamine synthesis. MIAMI cells from young and old individuals represent autologous human cell populations for the treatment of disorders of the skeletal and nervous systems and for applications in cell therapy and reparative medicine approaches.
AB - Marrow-isolated adult multilineage inducible (MIAMI) cells were differentiated in vitro to neuronal cells in a neurotrophin-dependent fashion. After induction, the cells revealed electrophysiological features similar to those observed in mature neurons. Primary early passage human MIAMI cells without any type of co-cultures with other cell types were used. The developmental program involved a multi-step process requiring the concerted action of brain-derived neurotrophic factor, nerve growth factor and depended on neurotrophin-3, after basic fibroblast growth factor withdrawal. MIAMI-derived neuron-like cells sequentially expressed the neuronal markers, developed a complex neurite outgrowth and arborization, and acquired electrophysiological characteristics similar to those observed in mature neurons. The young and old MIAMI-derived neuronal cells developed both inward and outward currents upon depolarization, similar to those observed in normal neurons. These results represent the earliest evidence that neurotrophin-3 can direct the differentiation of non-neural stem cells from human adult bone marrow stroma to neuron-like cells in vitro. Supplementing the aforementioned multi-step process with sonic hedgehog, fibroblast growth factor 8, and retinoic acid increased the expression of molecules involved in dopaminergic differentiation and of tyrosine hydroxylase, the rate limiting enzyme of dopamine synthesis. MIAMI cells from young and old individuals represent autologous human cell populations for the treatment of disorders of the skeletal and nervous systems and for applications in cell therapy and reparative medicine approaches.
KW - Bone marrow
KW - Differentiation
KW - Dopamine
KW - Neurotrophin-3
KW - Stem cell
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U2 - 10.1016/j.bone.2006.09.013
DO - 10.1016/j.bone.2006.09.013
M3 - Article
C2 - 17085092
AN - SCOPUS:33846169731
VL - 40
SP - 360
EP - 373
JO - Bone
JF - Bone
SN - 8756-3282
IS - 2
ER -