Acute myeloid leukemia (AML), also known as acute myelogenous leukemia, represents the most common type of leukemia in adults worldwide. Affecting the myeloid lineages of the blood, the onset of AML prompts a clonal expansion of immature blast cells in the peripheral blood and bone marrow that inhibits effective erythropoiesis and induces bone marrow failure.¹ Unfortunately, AML can progress rapidly and results in mortality in untreated patients within weeks or months. While therapeutic approaches for various hematological malignancies have recently seen significant improvement, AML patients still suffer from poor prognosis due to the high rate of recurrence after chemotherapeutic treatment, which has been attributed to the presence of residual chemoresistant leukemic cancer stem cells (or LSCs). Indeed, the transplantation of AML cells into immunodeficient mice prompted the first report of the involvement of cancer stem cells in human disease.² The general importance of the LSC component in AML has focused research toward the identification of those compounds that specifically target malignant hematopoietic stem and progenitor cells (HSPCs) while leaving their healthy counterparts unaffected³; however, this goal has been complicated by the reported phenotypic heterogeneity of LSCs in AML.^4-6 In our first Featured Article published this month in STEM CELLS, Shingai et al describe autonomous transforming growth factor-beta (TGF-β) signaling as a crucial molecular mechanism that mediates the heterogeneity of AML LSCs and a potential therapeutic target.⁷ In a Related Article published recently in STEM CELLS Translational Medicine, Knorr et al reported on the discovery of a chemotherapeutic agent with improved activity against AML-associated HSPCs employing a novel ex vivo method for assessing drug sensitivity.⁸

Studies in the 1970s highlighted the ability of urine-derived cells to survive and expand in culture,⁹ and the isolation of mesenchymal stem cell (MSC)-like cells with a male karyotype in the urine of a female patient who received a male donor kidney revealed their renal origin. Subsequent research then highlighted the transcriptomic similarity of so-called urine-derived stem cells (USCs) to renal parietal cells and renal progenitor cells to confirm their original residence in the kidney.¹⁰ The simple, cost-effective, and noninvasive nature of USC isolation, coupled with their high proliferation rate, ability to expand rapidly during in vitro culture, and enhanced ability to undergo myogenic, neurogenic, and endogenic differentiation when compared to other tissue-specific MSCs^{11, 12} has led to the proposal of USCs as an optimal cell source for various regenerative/reparative strategies. In a comparable manner to MSCs, USCs also secrete multiple trophic factors that recruit endogenous cells involved in tissue regeneration and induce immunomodulation to reduce inflammation and fibrosis.^{13, 14} Given this enormous potential, current research in the USC field has focused on deciphering the immunomodulatory mechanisms modulated by USCs and exploring their differentiation capacity. In our second Featured Article published this month in STEM CELLS, Zidan et al reveal that the immunomodulatory capabilities of USCs include the promotion of B lymphocyte functions—a finding that may alter our understanding of the immune environment of the kidney under normal and disease conditions.¹⁵ In a Related Article published recently in STEM CELLS Translational Medicine, Liu et al explored the in vitro and in vivo endothelial differentiation abilities of USCs and highlighted their potential application in tissue-engineered vascular regeneration or endothelial repair.¹⁶

急性髓细胞性白血病（AML），也称为急性骨髓性白血病，是全世界成人中最常见的白血病类型。AML的发作会影响血液的髓系，促使外周血和骨髓中未成熟胚细胞的克隆扩增，从而抑制有效的红细胞生成并诱发骨髓衰竭。^1个不幸的是，AML可以迅速发展，并在数周或数月内导致未经治疗的患者死亡。尽管最近各种血液恶性肿瘤的治疗方法已有显着改善，但AML患者由于化疗治疗后的高复发率而仍然预后较差，这归因于存在残留的化学耐药性白血病癌症干细胞（或LSC）。实际上，将AML细胞移植到免疫缺陷小鼠中引发了关于癌症干细胞参与人类疾病的第一个报道。^2个LSC成分在AML中的普遍重要性使研究集中于鉴定那些以恶性造血干细胞和祖细胞（HSPCs）为特异性，同时又不影响其健康对应物的化合物³；然而，据报道，在AML中LSC的表型异质性使该目标变得复杂。^4-6在本月发表于STEM CELLS的第一篇精选文章中，Shingai等人将自主转化生长因子-β（TGF-β）信号描述为介导AML LSCs异质性和潜在治疗靶标的关键分子机制。⁷在最近发表于《STEM CELLS转化医学》上的相关文章中，Knorr等人报道了一种使用新颖的离体方法评估药物敏感性的具有与AML相关的HSPC活性增强的化学治疗剂的发现。⁸

1970年代的研究强调了尿液衍生的细胞在培养中存活和扩增的能力，⁹并分离了接受男性供体肾脏的女性患者尿液中具有男性核型的间充质干细胞（MSC）样细胞。揭示了他们的肾脏起源。然后，随后的研究强调了所谓的尿源性干细胞（USC）与肾壁细胞和肾祖细胞的转录组学相似性，以证实它们最初在肾脏中的存在。¹⁰与其他组织特异性抗体相比，USC分离的简单，经济高效且无创性，再加上其高增殖速率，在体外培养过程中快速扩增的能力以及增强的进行肌原性，神经原性和内源性分化的能力MSC^11、12导致USC成为各种再生/修复策略的最佳细胞来源的提议。以与MSC相当的方式，USC还分泌多种营养因子，募集参与组织再生的内源性细胞并诱导免疫调节以减少炎症和纤维化。^[13，14]鉴于这种巨大的潜力，目前在USC领域的研究集中在破译USC调节的免疫调节机制并探索其分化能力。在本月发表于STEM CELLS的第二篇精选文章中Zidan等人揭示了USC的免疫调节能力包括促进B淋巴细胞的功能-这一发现可能会改变我们对正常和疾病条件下肾脏免疫环境的了解。¹⁵在最近发表于STEM CELLS Translational Medicine的相关文章中，Liu等人探索了USC的体外和体内内皮分化能力，并强调了它们在组织工程血管再生或内皮修复中的潜在应用。¹⁶