Rady Dina, Abbass Marwa M S, El-Rashidy Aiah A, El Moshy Sara, Radwan Israa Ahmed, Dörfer Christof E, Fawzy El-Sayed Karim M
Oral Biology Department, Faculty of Dentistry, Cairo University, Cairo, Egypt.
Stem Cells and Tissue Engineering Research Group, Faculty of Dentistry, Cairo University, Cairo, Egypt.
Stem Cells Int. 2020 Aug 11;2020:8837654. doi: 10.1155/2020/8837654. eCollection 2020.
Mesenchymal stem/progenitor cells (MSCs) are key players in regenerative medicine, relying principally on their differentiation/regeneration potential, immunomodulatory properties, paracrine effects, and potent homing ability with minimal if any ethical concerns. Even though multiple preclinical and clinical studies have demonstrated remarkable properties for MSCs, the clinical applicability of MSC-based therapies is still questionable. Several challenges exist that critically hinder a successful clinical translation of MSC-based therapies, including but not limited to heterogeneity of their populations, variability in their quality and quantity, donor-related factors, discrepancies in protocols for isolation, in vitro expansion and premodification, and variability in methods of cell delivery, dosing, and cell homing. Alterations of MSC viability, proliferation, properties, and/or function are also affected by various drugs and chemicals. Moreover, significant safety concerns exist due to possible teratogenic/neoplastic potential and transmission of infectious diseases. Through the current review, we aim to highlight the major challenges facing MSCs' human clinical translation and shed light on the undergoing strategies to overcome them.
间充质干/祖细胞(MSCs)是再生医学的关键参与者,主要依赖于它们的分化/再生潜能、免疫调节特性、旁分泌作用以及强大的归巢能力,且几乎不存在伦理问题。尽管多项临床前和临床研究已证明MSCs具有显著特性,但基于MSCs的疗法的临床适用性仍存在疑问。存在几个严重阻碍基于MSCs的疗法成功进行临床转化的挑战,包括但不限于其群体的异质性、质量和数量的变异性、供体相关因素、分离、体外扩增和预修饰方案的差异,以及细胞递送、给药和细胞归巢方法的变异性。各种药物和化学物质也会影响MSCs的活力、增殖、特性和/或功能。此外,由于可能的致畸/致癌潜力和传染病传播,存在重大安全问题。通过本综述,我们旨在突出MSCs临床转化面临的主要挑战,并阐明正在采取的克服这些挑战的策略。