Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies
| Autor: | David W. Grainger, Teruo Okano, Celia M. Dunn, Sumako Kameishi |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Stromal cell
medicine.medical_treatment 0206 medical engineering Cell Biomedical Engineering Cell- and Tissue-Based Therapy Graft vs Host Disease 02 engineering and technology Disease Bioinformatics Mesenchymal Stem Cell Transplantation Biochemistry Biomaterials Cell therapy Immunomodulation Immune system medicine Humans Molecular Biology business.industry Mesenchymal stem cell Mesenchymal Stem Cells General Medicine 021001 nanoscience & nanotechnology 020601 biomedical engineering Clinical trial Cytokine medicine.anatomical_structure 0210 nano-technology business Biotechnology |
| Zdroj: | Acta biomaterialia. 133 |
| ISSN: | 1878-7568 |
| Popis: | Mesenchymal stromal cells (MSCs) have gained immense attention over the past two decades due to their multipotent differentiation potential and pro-regenerative and immunomodulatory cytokine secretory profiles. Their ability to modulate the host immune system and promote tolerance has prompted several allogeneic and autologous hMSC-based clinical trials for the treatment of graft-versus-host disease and several other immune-induced disorders. However, clinical success beyond safety is still controversial and highly variable, with inconclusive therapeutic benefits and little mechanistic explanation. This clinical variability has been broadly attributed to inconsistent MSC sourcing, phenotypic characterization, variable potency, and non-standard isolation protocols, leading to functional heterogeneity among administered MSCs. Homogeneous MSC populations are proposed to yield more predictable, reliable biological responses and clinically meaningful properties relevant to cell-based therapies. Limited comparisons of heterogeneous MSCs with homogenous MSCs are reported. This review addresses this gap in the literature with a critical analysis of strategies aimed at decreasing MSC heterogeneity concerning their reported immunomodulatory profiles. STATEMENT OF SIGNIFICANCE: This review collates, summarizes, and critically analyzes published strategies that seek to improve homogeneity in immunomodulatory functioning MSC populations intended as cell therapies to treat immune-based disorders, such as graft-vs-host-disease. No such review for MSC therapies, immunomodulatory profiles and cell heterogeneity analysis is published. Since MSCs represent the most clinically studied experimental cell therapy platform globally for which there remains no US domestic marketing approval, insights into MSC challenges in therapeutic product development are imperative to providing solutions for immunomodulatory variabilities. |
| Databáze: | OpenAIRE |
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