Multipotent adult progenitor cells (MAPCs), a plastic‐adherent bone marrow‐derived population of human multipotent adult stem cells, can undergo long‐term culture expansion without significant losses in potency or genomic and epigenetic stability.¹ Furthermore, MAPCs, which are distinct from mesenchymal stem cells, do not evoke an immune response and display potent immunomodulatory/anti‐inflammatory and regenerative properties.^{2, 3} The therapeutic potential of MAPC therapy has been supported by the improvements to neurological outcomes observed in preclinical models of hypoxic‐ischemic encephalopathy, traumatic brain and spinal cord injury, and stroke, among other conditions. Of particular note, a clinical‐grade MAPC product known as MultiStem (Athersys, Inc, Cleveland, Ohio) is currently under evaluation for safety and efficacy in a double‐blind, placebo‐controlled clinical trial for the treatment of ischemic stroke in human patients.⁴ These promising results have driven the further exploration of MAPC therapy as a means to treat brain injuries and improve neurodevelopmental outcomes in preterm neonates, while complementary research has sought to understand the mechanisms by which MAPC therapy improves outcomes. In our first Featured Article published this month in STEM CELLS Translational Medicine, Gussenhoven et al report that systemic MAPC therapy reduces cerebellar injury after asphyxia in fetal sheep in a study that extends previous observations that MAPCs afford cerebral neuroprotection.⁵ In a Related Article published recently in STEM CELLS, Yang et al discovered that systemic MAPC therapy enhanced recovery after stroke by altering the expression of immune‐related genes and reducing pro‐inflammatory signaling in the spleen.⁶

Yes‐associated protein 1 (YAP1 or YAP) is a transcriptional coactivator of the Hippo pathway that transduces mechanical cues such as extracellular matrix (ECM) rigidity, strain, and shear stress to regulate biological processes that include cell growth and fate decision, organ size control, and regeneration.⁷ The activation of the Hippo signaling pathway prompts the phosphorylation and inactivation of YAP1; however, the inhibition of Hippo signaling prevents YAP1 phosphorylation and promotes the relocation of YAP1 from the cytoplasm to the nucleus, where it functions as a transcriptional coactivator for genes associated with cell proliferation, survival, mobility, stemness, and differentiation. Multiple studies have highlighted an important role for YAP1 in controlling the differentiation of various stem and progenitor cell types ‐ specifically, activated YAP1 supports the maintenance of the self‐renewing state of pluripotent stem cells⁸ and the proliferation of tissue‐resident stem cells,⁹ whereas YAP1 inactivation can promotes efficient stem cell differentiation. Therefore, a deeper understanding of YAP1 function in stem cell biology may permit the enhanced in vitro expansion of stem cells and their efficient differentiation into therapeutically relevant cell types. In our second Featured Article published this month in STEM CELLS Translational Medicine, Yamashita et al demonstrate that the inactivation of YAP1 during the differentiation of human induced pluripotent stem cells (iPSCs) on a laminin‐fragment culture substrate significantly improves chondrogenesis and cartilage formation.¹⁰ In a Related Article published recently in STEM CELLS, Xia et al characterized YAP1 as a crucial mechanotransduction signaling mediator that promotes the expansion of inner ear progenitor cells (IEPCs) via the regulation of Wnt/β‐catenin activity.¹¹

多能成体祖细胞 (MAPC) 是一种塑料粘附的骨髓来源的人类多能成体干细胞群，可以进行长期培养扩增，而不会显着丧失效力或基因组和表观遗传稳定性。¹此外，与间充质干细胞不同的 MAPC 不会引起免疫反应，并显示出有效的免疫调节/抗炎和再生特性。^2、3MAPC 疗法的治疗潜力得到了在缺氧缺血性脑病、创伤性脑和脊髓损伤以及中风等疾病的临床前模型中观察到的神经学结果改善的支持。特别值得注意的是，临床级 MAPC 产品 MultiStem (Athersys, Inc, Cleveland, Ohio) 目前正在一项用于治疗人类缺血性卒中的双盲、安慰剂对照临床试验中评估其安全性和有效性. ⁴这些有希望的结果推动了 MAPC 治疗作为治疗脑损伤和改善早产新生儿神经发育结果的手段的进一步探索，而补充研究试图了解 MAPC 治疗改善结果的机制。在我们本月发表在STEM CELLS Translational Medicine上的第一篇专题文章中，Gussenhoven 等人报告称，全身 MAPC 治疗可减少胎羊窒息后的小脑损伤，这项研究扩展了之前关于 MAPC 提供脑神经保护的观察结果。⁵在最近发表在STEM CELLS上的相关文章中, Yang 等人发现全身 MAPC 治疗通过改变免疫相关基因的表达和减少脾脏中的促炎信号传导来促进中风后的恢复。⁶

Yes 相关蛋白 1（YAP1 或 YAP）是 Hippo 通路的转录共激活因子，可转导细胞外基质 (ECM) 刚性、应变和剪切应力等机械信号，以调节包括细胞生长和命运决定、器官大小在内的生物过程控制和再生。⁷Hippo信号通路的激活促使YAP1的磷酸化和失活；然而，抑制 Hippo 信号通路会阻止 YAP1 磷酸化并促进 YAP1 从细胞质重新定位到细胞核，在细胞核中它充当与细胞增殖、存活、移动、干性和分化相关的基因的转录共激活因子。多项研究强调了 YAP1 在控制各种干细胞和祖细胞类型分化中的重要作用 - 具体而言，激活的 YAP1 支持多能干细胞自我更新状态的维持⁸和组织驻留干细胞的增殖⁹而 YAP1 失活可以促进有效的干细胞分化。因此，更深入地了解 YAP1 在干细胞生物学中的功能可能会增强干细胞的体外扩增及其有效分化为治疗相关细胞类型的能力。在我们本月发表在STEM CELLS Translational Medicine上的第二篇专题文章中，Yamashita 等人证明，在层粘连蛋白片段培养基质上人类诱导多能干细胞 (iPSC) 分化过程中 YAP1 的失活显着改善了软骨形成和软骨形成。¹⁰在最近发表在STEM CELLS上的相关文章中, Xia 等人将 YAP1 描述为一种重要的机械转导信号介质，通过调节 Wnt/β-catenin 活性促进内耳祖细胞 (IEPC) 的扩增。¹¹