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Experimental therapeutics: preclinical
B14 Neurotrophic factors secreting mesenchymal stem cells attenuate quinolinic acid induced striatal lesion model suggesting autologous therapy for HD
  1. O Sadan,
  2. R Barzilay,
  3. E Melamed,
  4. D Offen
  1. Laboratory of Neurosciences, Felsenstein Medical Research Centre, Sackler Faculty of Medicine, Tel Aviv University, Israel

Abstract

Background We have been studying the potential of utilising the patients' own bone marrow derived mesenchymal stem cells (MSCs) which are transformed into cellular vectors secreting neurotrophic factors (NTF+ cells) in order to protect diseased neurons. Differentiated cells were shown to produce and secrete higher levels of BDNF and GDNF compared with naive MSCs.

Aims To evaluate the efficacy of NTF+ cell based therapy for the quinolinic acid (QA) induced striatal model for excitotoxicity. To evaluate the capability of cultivating MSCs from HD patients, transforming them into NTF+ cells and transplanting them into the QA model.

Methods Human MSC went through a two phase medium based differentiation protocol containing N2, growth factors, IBMX and cAMP. The protocol's output was assessed using immunocytochemistry and ELISA analysis of the medium post differentiation. Rats were treated with 150 nmol QA injected into the left striatum. A total of 450 000 cells (either MSCs of NTF+ cells) were transplanted into the lesioned striatum. Behavioural assessment included apomorphine induced rotations, followed by a histological study.

Results Transplanting NTF+ cells, but not naive MSCs, ameliorated apomorphine induced rotations by over 80%. Moreover, we found that NTF+ cells transplantation reduced QA induced striatal atrophy. One of the inherent advantages of the use of MSCs is the possibility of autotransplantation. Indeed, MSC obtained from four Huntington's disease (HD) patients demonstrated similar membrane markers and differentiation capacity. Moreover, in the QA induced striatal lesion model, we found that HD patients' NTF+ cells altered apomorphine induced rotational behaviour as well as cells derived from healthy controls.

Conclusions Our preliminary data suggest that NTF+ cells may be utilised for cellular autologous treatment for HD in the future. Further research is needed in order to fully prove its efficacy, mechanism and mode of delivery in various animal models for HD.

  • mesenchymal stem cells
  • neurotrophic factors
  • quinolinic acid
  • patient derived stem cells

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