Rodrigo Pinheiro Araldi

By Irina Kerkis, Rodrigo Pinheiro Araldi, Cristiane Valverde Wenceslau and Thais Biude Mendes

Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of CAG repeats in the huntingtin gene. The disease causes the progressive degeneration of neurons affecting particularly the medium spiny neurons (MSNs) within the striatum. The mHtt inclusions promote neurodegeneration. However, the mHtt can spread to different brain areas through exosomes. For this reason, it is not surprising that HD causes motor, cognitive and neuropsychiatric dysfunctions. To date there is no treatment able to modify the natural history of the disease. In this sense, the advanced cellular therapy, based on the therapeutic use of mesenchymal stem cells (MSCs) emerges as a potential candidate for HD treatment. This is because, the MSCs produce many critical therapeutic molecules which act in multiple cellular and molecular targets. Moreover, in addition, advanced cell therapy is a unique approach that could provides neuroprotection and neuroregeneration. However, the current discovery that the MSC mechanism of action is mediated by exosomes, have encouraged scientist to explore the therapeutic potential of the cell-free therapy. Based on this, we revisited the HD pathophysiology, areas. Providing evidence that MSC and MSC-derived exosomes can be used to change the natural history of HD.

Part of the book: From Pathophysiology to Treatment of Huntington's Disease

By Rodrigo Pinheiro Araldi, João Rafael Dias Pinto and Irina Kerkis

Cellular and cell-free therapies have provided novel therapeutic opportunities for treating various incurable diseases. This is because the mesenchymal stromal/stem cells (MSCs) produce a plethora of bioactive molecules able to target different biological pathways through extracellular vesicle-mediated paracrine mechanisms simultaneously. However, to share transcriptomic signatures with their origin tissue, it is expected that each MSC population has a unique molecular profiler. In this sense, to analyze the transcriptome of therapeutic cells, it is crucial to identify the molecular profiler of these cells to predict the potential clinical benefits promoted by these cells. Herein, we discuss the application of high-throughput RNA-sequencing (RNA-Seq) in the Pharma Intelligence Era, discussing and exemplifying how the combination of molecular biology with Analytics can revolutionize the Research, Development, & Innovation (RD&I) of advanced medicinal products.

Part of the book: Recent Update on Mesenchymal Stem Cells

By Irina Kerkis, Cristiane Valverde Wenceslau and Rodrigo Pinheiro Araldi

Dental pulp stem cells (DPSCs) are a special mesenchymal stem cell (MSC) type. These cells can be isolated from the dental pulp (DP) of deciduous, adult, and wisdom teeth. Stem cells from milk/baby teeth fall naturally, representing an advantageous source of young stem cells. These cells are less studied than MSCs from bone marrow, adipose tissue, and umbilical cord. MSCs from these sources are currently widely used in clinical studies. However, obtaining significant quantities of DPSCs from one donor is still challenging, thus limiting their systemic application in patients, which requires doses starting from 5 × 10⁵ per kg of weight and higher. In this chapter, we would like to share our experience of more than 20 years in the isolation and scaling up of DPSC from deciduous teeth. We will also provide information about their in vitro growth, differentiation, and therapeutic potential observed in animal models that mimic human diseases or injuries in preclinical studies. Finally, we will discuss our experience of DPSC production under good manufacturing practice conditions and their use in regulated clinical studies in Brazil for Huntington’s disease.

Part of the book: Recent Update on Mesenchymal Stem Cells