Microanatomical evidences for potential of mesenchymal stem cells in amelioration of striatal degeneration

Abstract

Huntington's disease is an inherited neurodegenerative disorder, characterized by loss of spiny neurons in the striatum and cortex, which usually happens in the third or fourth decades of life. In advanced form of the disease, progressive striatum atrophy happens and medium spiny neurons, which occupy more than 80% of the striatum, become atrophic. Gradually, the atrophy expands to the neocortex and other regions of the brain. To our knowledge, there is no effective therapeutic strategy for diminishing the motor disorders of Huntington's disease. In recent years, cellular transplantation has been an effective therapeutic method for neurodegenerative diseases. In the present study, the potential of bone marrow derived mesenchymal stem cells in amelioration of striatal degeneration was assessed in animal model of Huntington's disease. After unilateral lesion in striatum was caused by quinolinic acid (QA), bone marrow derived mesenchymal stem cells, which were isolated and purified from 4-6 weeks old rats, were transplanted into the damaged striatum. After 9 weeks of transplantation, the volume of striatum, lateral ventricles and hemispheres were measured in control (normal) and test (QA injected + cell transplanted) groups. After volume determination, the atrophy percentage of both striatum and damaged hemisphere and volume extension of lateral ventricles were calculated. Histologic results showed significant difference in amount of striatum atrophy between sham (only QA injected) and test groups. These results confirm the potential of bone marrow derived mesenchymal stem cells in treatment of microanatomical defects in motor disorders of Huntington's disease. According to our results, cell therapy by means of bone marrow derived adult stem cells could be considered as a good candidate for treatment of neurodegenerative diseases, especially Huntington's disease.

Mesenchymal stem cells as therapeutic agents and potential targeted gene delivery vehicle for brain diseases

“…Transplanting autologous bone marrow stem cells in the damaged striatum of a rat HD model significantly reduced working memory deficits [59]. Meanwhile, the volume of the lateral ventricle returned to a significantly smaller size, approaching the normal contralateral ventricle after MSCs implantation [60]. Mesenchymal stem cell transplantation may help stabilize the striatal environment by producing anti-inflammatory cytokines and neurotrophic factors.…”

Genetically Engineered Mesenchymal Stem Cells as a Proposed Therapeutic for Huntington’s Disease

“…Bantubungi et al [72] found that the lesioned environment of the striatum favored the proliferation and intralesional distribution of MSC. Several groups have shown that striatal atrophy in models of HD is accompanied by the subsequent enlargement of lateral ventricles [73, 74]. The reduction in volume of the lateral ventricle can thus be a good indicator of repair in HD correction studies.…”

“…The reduction in volume of the lateral ventricle can thus be a good indicator of repair in HD correction studies. Amin et al [73] demonstrated that after MSC implantation into the striata of rats with a unilateral damage model of HD, striatal atrophies were significantly reduced. Consequently, the volume of the lateral ventricle returned to a significantly smaller size, approaching the normal contralateral ventricle.…”

Advances in the Combined Use of Adult Cell Therapy and Scaffolds for Brain Tissue Engineering

“…More recently, transplantation of MSCs, either intracerebrally or intravenously, resulted in a decreased atrophy of lesioned rat striatum (Amin et al, 2008) and in some functional benefits (Edalatmanesh et al, 2009) even though only a fraction of cells (1 %) expressed neural phenotypes. Thus, it was suggested that MSCs, by producing growth factors, allowed surviving cells within the caudate nucleus to function more efficiently and to facilitate other compensatory responses (Dunbar et al, 2006).…”