Concise Review: The Use of Stem Cells for Understanding and Treating Huntington's Disease

Abstract

Two decades ago, researchers identified that a CAG expansion mutation in the huntingtin (HTT) gene was involved in the pathogenesis of Huntington's disease (HD). However, since the identification of the HTT gene, there has been no advance in the development of therapeutic strategies to prevent or reduce the progression of HD. With the recent advances in stem cell biology and human cell reprogramming technologies, several novel and exciting pathways have emerged allowing researchers to enhance their understanding of the pathogenesis of HD, to identify and screen potential drug targets, and to explore alternative donor cell sources for cell replacement therapy. This review will discuss the role of compensatory neurogenesis in the HD brain, the use of stem cell-based therapies for HD to replace or prevent cell loss, and the recent advance of cell reprogramming to model and/or treat HD. These new technologies, coupled with advances in genome editing herald a promising new era for HD research with the potential to identify a therapeutic strategy to alleviate this debilitating disorder. Stem Cells 2018;36:146-160.

Therapeutic effects of stem cells in rodent models of Huntington's disease: Review and electrophysiological findings

“…A variety of stem cells have been implanted in HD rodent models (Table ) to assess their potential therapeutic ability, including mesenchymal stem cells (MSCs), fetal neural stem cells, or neural cell types differentiated from induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) (see also recent reviews in Refs. ).…”

“…The emergent field of regenerative medicine offers renewed hope for cell replacement therapies and provides new approaches for a potential cure. In particular, the use of human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSC)‐derived products has generated widespread interest for neurodegenerative diseases including HD . In this review, we present recent advances in the use of various stem cell types in animal models of HD.…”

“…In particular, the use of human embryonic stem cells (hESCs) and induced pluripotent stem cell (iPSC)-derived products has generated widespread interest for neurodegenerative diseases including HD. [50][51][52] In this review, we present recent advances in the use of various stem cell types in animal models of HD. In addition, we provide further electrophysiological characterization of ESI-017 human neural stem cells (hNSCs), a good manufacturing practice (GMP)-grade cell line which has already shown promising results in two HD mouse models.…”

TSC patient-derived isogenic neural progenitor cells reveal altered early neurodevelopmental phenotypes and rapamycin-induced MNK-eIF4E signaling

“…Further, the inability to establish expandable human cell lines derived from various TSC-associated lesions, along with genetically matched control cell lines has made it difficult to define the precise pathogenic mechanisms involved in TSC. Patient-specific induced pluripotent stem cells (iPSCs) derived from somatic cells, followed by differentiation into specific cell types, are rapidly evolving to be powerful for disease modeling to study pathophysiology and to identify treatments [13][14][15][16][17]. More importantly, the emergence of powerful genome editing techniques has made it possible to generate isogenic pairs of disease and control human iPSCs that differ only with respect to disease-causing gene mutations [18][19][20].…”

Now More Than Ever: The Importance of Reporting Evidence-Based Science

“…Among our most downloaded and cited articles for 2018 were several outstanding concise reviews, which are an excellent way to get "up to speed" in a specific field. The topics included Cell Therapy for Critical Limb Ischemia [6], Clinical Application of Chimeric Antigen Receptor T Cell Therapies [7], Human Pluripotent Stem Cells to Produce Cell-Based Cancer Immunotherapy [8], Age-Related Clonal Hematopoiesis [9], Wnt Signaling Pathways in Skin Development [10], Three-Dimensional Organoids as Preclinical Models [11], Assessing the Genome Integrity of Human Induced Pluripotent Stem Cells [12], Stem Cell-Based Therapy in Myocardial Repair [13], and The Use of Stem Cells for Understanding and Treating Huntington's Disease [14]. These concise reviews are from experts in their respective fields and cite evidence-based research, helping to move the respective fields forward in a reliable manner.…”