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

Abstract

There is much interest in the use of mesenchymal stem cells/marrow stromal cells (MSC) to treat neurodegenerative disorders, in particular those that are fatal and difficult to treat, such as Huntington’s disease. MSC present a promising tool for cell therapy and are currently being tested in FDA-approved phase I–III clinical trials for many disorders. In preclinical studies of neurodegenerative disorders, MSC have demonstrated efficacy, when used as delivery vehicles for neural growth factors. A number of investigators have examined the potential benefits of innate MSC-secreted trophic support and augmented growth factors to support injured neurons. These include overexpression of brain-derived neurotrophic factor and glial-derived neurotrophic factor, using genetically engineered MSC as a vehicle to deliver the cytokines directly into the microenvironment. Proposed regenerative approaches to neurological diseases using MSC include cell therapies in which cells are delivered via intracerebral or intrathecal injection. Upon transplantation, MSC in the brain promote endogenous neuronal growth, encourage synaptic connection from damaged neurons, decrease apoptosis, reduce levels of free radicals, and regulate inflammation. These abilities are primarily modulated through paracrine actions. Clinical trials for MSC injection into the central nervous system to treat amyotrophic lateral sclerosis, traumatic brain injury, and stroke are currently ongoing. The current data in support of applying MSC-based cellular therapies to the treatment of Huntington’s disease is discussed.

The Key Regulatory Roles of the PI3K/Akt Signaling Pathway in the Functionalities of Mesenchymal Stem Cells and Applications in Tissue Regeneration

“…Secreted neuron growth factors such as nerve growth factor, BDNF, and glial cell line-derived neurotrophic factor also facilitate the recovery from Alzheimer's disease, Huntington's disease, Parkinson's disease, multiple sclerosis, and Krabbe's disease. 105 Evidence has shown that the MSC's ability to secrete cytokines is regulated by PI3K/Akt activity. SDF-1 has been shown to increase the secretion of cytokines by MSCs, and this effect is mediated by the PI3K/Akt pathway.…”

Infrared light as a potential therapeutic approach for neurodegeneration

“…Although no fundamental treatment has been established for blocking or even delaying the progression of SCA symptoms, a biochemical approach using mesenchymal stem cells (MSCs) is currently being tested in clinical trials for SCA as well as for other nervous system diseases [18] such as multiple sclerosis [19] and spinal cord injury [20]. In a study using 14 cases of SCA patients [21], the intrathecal injection of umbilical cord MSCs could improve the movement ability and quality of daily life 1 month after the treatment, as evidenced by scores of the International Cooperative Ataxia Rating Scale (ICARS) and Activity of Daily Living Scale (ADL).…”

Nörodejeneratif Hastalıklarda Mezenkimal Kök Hücre Uygulamaları

“…Hastalığın huntingtin genindeki poliglutamin ekspresyonundaki patolojiye bağlı olduğu ortaya konmuştur. Hastalık serebral korteks, bazal ganglion, hipokampus ve hipotalamusda nöronal hücre kaybı sonucu koreik hareketler, kavramsal karışıklık ve psikiyatrik bozukluklarla seyretmektedir 60,61 . Hastalığın belirgin bir tedavisi bulunmamaktadır bu nedenle kök hücre nakli çalışmaları bir umut oluşturmaktadır.…”