Strategies to Improve the Quality and Freshness of Human Bone Marrow-Derived Mesenchymal Stem Cells for Neurological Diseases

Abstract

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for their application to manage various neurological diseases, owing to their anti-inflammatory, immunomodulatory, paracrine, and antiapoptotic ability, as well as their homing capacity to specific regions of brain injury. Among mesenchymal stem cells, such as BM-MSCs, adipose-derived MSCs, and umbilical cord MSCs, BM-MSCs have many merits as cell therapeutic agents based on their widespread availability and relatively easy attainability and in vitro handling. For stem cell-based therapy with BM-MSCs, it is essential to perform ex vivo expansion as low numbers of MSCs are obtained in bone marrow aspirates. Depending on timing, before hBM-MSC transplantation into patients, after detaching them from the culture dish, cell viability, deformability, cell size, and membrane fluidity are decreased, whereas reactive oxygen species generation, lipid peroxidation, and cytosolic vacuoles are increased. Thus, the quality and freshness of hBM-MSCs decrease over time after detachment from the culture dish. Especially, for neurological disease cell therapy, the deformability of BM-MSCs is particularly important in the brain for the development of microvessels. As studies on the traditional characteristics of hBM-MSCs before transplantation into the brain are very limited, omics and machine learning approaches are needed to evaluate cell conditions with indepth and comprehensive analyses. Here, we provide an overview of hBM-MSCs, the application of these cells to various neurological diseases, and improvements in their quality and freshness based on integrated omics after detachment from the culture dish for successful cell therapy.

Colony-forming potential of murine bone marrow-derived progenitor cells in experimental neurodegenerative pathology and under the impact of melatonin in vivo or in vitro

“…Parkinson's disease (PD) and multiple sclerosis are chronic, progressive neurodegenerative pathologies that are quite common in Ukraine and tend to increase [1,2]. Today, the transplantation of multipotent mesenchymal stromal cells (MMSCs) from various sources, in particular bone marrow, is an important direction of cell therapy for the above-mentioned pathologies [3][4][5]. This is related to the biological properties of MMSCs, namely the ability to multilineage differentiation, the synthesis of neurotrophic factors, anti-inflammatory, antioxidant and immunomodulatory effects.…”

“…Bone marrow-derived hematopoietic stem cells (HSCs), which are differentiated in lymphoid and myeloid directions, are also promising for the use in cell therapy of multiple sclerosis, which is explained by their influence on the immune mechanisms of the development of this pathology [6,7]. Under the influence of damaging factors and the development of pathological processes, changes in the biological properties of stem cells can be reflected in their regenerative potential [4]. Therefore, it is urgent to search for medicinal products that, under the conditions of the development of neurodegenerative pathology, are able to improve the biological characteristics of stem cells.…”

Cerebrospinal Fluid Metabolome in Parkinson’s Disease and Multiple System Atrophy

“…Machine learning is used for handling large-scale datasets, including integrated omics data [105]. Machine learning is divided into supervised learning, unsupervised learning, and reinforcement learning [55,110]. Supervised learning typically includes support vector machine (SVM), K-nearest neighbor (KNN) [111].…”

“…Unsupervised learning involves training with unlabeled data and grouping them into similar groups [112]. In the unsupervised learning clustering algorithm, there are K-means, K-medoids, and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) clustering [55,110]. In addition, principal component analysis (PCA) facilitates data analysis by reducing the dimensions of the data distribution [113].…”

Human Bone Marrow-Derived Mesenchymal Stem Cell Applications in Neurodegenerative Disease Treatment and Integrated Omics Analysis for Successful Stem Cell Therapy

“…In clinical applications, the quality of hBM-MSCs should be analyzed after cell detachment from the culture dish [12,15,56], because cell quality is an essential factor for therapeutic effects. However, there are limitations to the traditional methods used to evaluate the quality and freshness of cells prior to transplantation of hBM-MSCs into humans, such as trypan blue staining or fluorescence-activated cell sorting (FACS) [56,57].…”