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オカノ テルオ
Okano Teruo
岡野 光夫 所属 医学研究科 医学研究科 (医学部医学科をご参照ください) 職種 評議員 |
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| 論文種別 | 総説 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Strategies to address mesenchymal stem/stromal cell heterogeneity in immunomodulatory profiles to improve cell-based therapies. |
| 掲載誌名 | 正式名：Acta biomaterialia 略 称：Acta Biomater ISSNコード：18787568/17427061 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 133,pp.114-125 |
| 著者・共著者 | DUNN Celia M.†, KAMEISHI Sumako, GRAINGER David W*, OKANO Teruo* |
| 担当区分 | 最終著者,責任著者 |
| 発行年月 | 2021/10/01 |
| 概要 | 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. |
| DOI | 10.1016/j.actbio.2021.03.069 |
| PMID | 33857693 |