Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington’s disease

Abstract

Background Human embryonic stem cells (hESCs) transplantation had shown to provide a potential source of cells in neurodegenerative disease studies and lead to behavioral recovery in lentivirus transfected or, toxin-induced Huntington's disease (HD) rodent model. Here, we aimed to observe if transplantation of superparamagnetic iron oxide nanoparticle (SPION)-labeled hESCs could migrate in the neural degenerated area and improve motor dysfunction in an AAV2-Htt171-82Q transfected Huntington rat model. Methods All animals were randomly allocated into three groups at first: HD group, sham group, and control group. After six weeks, the animals of the HD group and sham group were again divided into two subgroups depending on animals receiving either ipsilateral or contralateral hESCs transplantation. We performed cylinder test and stepping test every two weeks after AAV2-Htt171-82Q injection and hESCs transplantation. Stem cell tracking was performed once per two weeks using T2 and T2*-weighted images at 4.7 Tesla MRI. We also performed immunohistochemistry and immunofluorescence staining to detect the presence of hESCs markers, huntingtin protein aggregations, and iron in the striatum. Results After hESCs transplantation, the Htt virus-injected rats exhibited significant behavioral improvement in behavioral tests. SPION labeled hESCs showed migration with hypointense signal in MRI. The cells were positive with βIII-tubulin, GABA, and DARPP32. Conclusion Collectively, our results suggested that hESCs transplantation can be a potential treatment for motor dysfunction of Huntington's disease.

The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review

“…The differences were more pronounced in animals that received only one administration of hIDPSC. These results suggest that intravenous administration of hIDPSCs can restore the expression of BDNF, DARPP32, and D2R, promoting neuroprotection and neurogenesis (Islam et al 2021 ). Other scientists have also reached similar conclusions, conducting analogous studies on mouse models (Wenceslau et al 2022 ).…”

Nanotherapeutic and Stem Cell Therapeutic Strategies in Neurodegenerative Diseases: A Promising Therapeutic Approach

“… 52 , 116 In recent years, SPION-labeled stem cell tracking for MRI has been used in studies on several neurodegenerative diseases, including AD, PD, and HD. 84 , 117–120 …”

“…52,116 In recent years, SPION-labeled stem cell tracking for MRI has been used in studies on several neurodegenerative diseases, including AD, PD, and HD. 84,[117][118][119][120] To reduce the accumulation and cytotoxicity of SPIONs in tissues and maximize biocompatibility, biopolymers are usually coated on their surface. 83 Hour et al labeled Wharton's jelly-derived MSCs with dextran-coated SPIONs and delivered them magnetically to the hippocampal region of AD rat brains.…”

Human striatal progenitor cells that contain inducible safeguards and overexpress BDNF rescue Huntington’s disease phenotypes in R6/2 mice

“…Cellular methods of NT delivery, particularly stem cell-based therapies, have produced promising therapeutic effects for many brain disorders and neurodegenerative diseases, including Parkinson's disease and HD [13][14][15] . Stem cell-based therapies can potentially target multiple disease mechanisms by replacing degenerated cells and/or secreting neuroprotective factors, such as NTs, a large number of HD preclinical studies have used this approach 13,[15][16][17][18][19][20][21] . Most of these studies utilized murine stem cells, typically mesenchymal stem cells, intracranially transplanted in HD rodent models and attributed the observed beneficial effects to trophic factors, primarily BDNF.…”