Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons

Valerie M. Tatard, Gianluca D'Ippolito, Sylma Diabira, Alexander Valeyev, John Hackman, Micheline McCarthy, Thomas Bouckenooghe, Philippe Menei, Claudia N. Montero-Menei, Paul C. Schiller

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)360-373
Number of pages14
JournalBone
Volume40
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • Bone marrow
  • Differentiation
  • Dopamine
  • Neurotrophin-3
  • Stem cell

ASJC Scopus subject areas

  • Physiology
  • Hematology

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    Tatard, V. M., D'Ippolito, G., Diabira, S., Valeyev, A., Hackman, J., McCarthy, M., Bouckenooghe, T., Menei, P., Montero-Menei, C. N., & Schiller, P. C. (2007). Neurotrophin-directed differentiation of human adult marrow stromal cells to dopaminergic-like neurons. Bone, 40(2), 360-373. https://doi.org/10.1016/j.bone.2006.09.013