Bone marrow non-mesenchymal mononuclear cells induce functional differentiation of neuroblastoma cells
© Phruksaniyom et al.; licensee BioMed Central Ltd. 2013
Received: 14 January 2013
Accepted: 16 March 2013
Published: 3 April 2013
Less is known about the non-mesenchymal mononuclear cell fraction of human bone marrow on functional adaptation of neuroblastoma cells. Using immunocytochemistry, we showed that bone-marrow mononuclear cell (BMMC)-conditioned medium can induce tyrosine hydroxylase expression in neuroblastoma cells, which is similar to the effect of retinoic acid. Using quantitative RT-PCR, we showed that NGF, CNTF, and BDNF mRNAs were detected in unfractionated BMMC populations from all human donors at different expression levels. Our results suggest that cells of the non-mesenchymal mononuclear cell fraction can induce functional adaptation of neuroblastoma cells, probably via their secreted trophic factors.
KeywordsBone-marrow mononuclear cells Neuroblastoma cells Tyrosine hydroxylase Trophic factors Neuronal differentiation
To the editor
Many studies investigating the possible therapeutic role of bone marrow-derived stem cells (BMDCs) used a specific subpopulation: the bone marrow mesenchymal stromal cells (MSCs) obtained after several weeks in cultures , or the mononuclear fraction (BMMC; bone marrow mononuclear cells) obtained immediately after aspiration. Cells of the hematopoietic stem cell fraction, when transplanted into lesions of a developing spinal cord in a chicken embryo, can differentiate into neurons . The capacity of BMMCs to generate neural cells is poorly characterized. Several studies indicate an overlap in the molecular programs for hematopoiesis and neuropoiesis in mice [3, 4]. Primary CD34+ human hematopoietic stem cells (HSCs) have been shown to express mRNA for a number of proteins that are used by neurons .
Evidence has indicated that human SH-SY5Y neuroblastoma cells changed into neuron-like phenotypes with reduced proliferation by all-trans retinoic acid (ATRA) , and treatment with RA increased protein expression of tyrosine hydroxylase (TH) in neuroblastoma cells . Using a co-culture method, human MSCs promoted the survival and neuritogenesis of neuroblastoma cells, similar to that of ATRA . Less is known about the mononuclear cell fraction of human bone marrow on functional adaptation of neuroblastoma cells.
Expression of TH, the enzyme involved in the first step of the biosynthesis pathway of dopamine and noradrenaline, in SH-SY5Y cells by BMMC-conditioned media suggests the functional differentiation of the cells. ATRA can also induce responsiveness to BDNF in SH-SY5Y cells . Our results imply that expression and secretion of BDNF from cells in the mononuclear fraction may explain the similar effects of RA and BMMC-conditioned media. BMDCs constitutively synthesize and secrete NGF, BDNF, and CNTF. Multiple cell types, however, are present in the BMMC fraction. Primary CD34+ human HSCs express mRNA for a number of proteins, including receptors for trophic factors and other mediators involved in the development of neurons . Most of the CD34+ cells are progenitors for myeloid and lymphoid lineages, which express some trophic factors, such as CNTF , that were also observed in our quantitative RT-PCR results. Further studies are required to quantify the contribution of trophic factors to BMMC-induced effects on functional adaptation of neuroblastoma cells, which could have clinical relevance in treatment of neuroblastoma.
This work was supported by a grant from Faculty of Science, Mahidol University to PD.
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