Lifelong homeostasis of bone marrow is maintained by the resident stem cells that include the quiescent very small embryonic-like stem cells (VSELs) and lineage restricted, tissue committed ‘progenitors’ hematopoietic stem cells (HSCs). Niche providing mesenchymal stromal cells (MSCs) regulate the function of VSELs/HSCs by providing crucial paracrine support. Any dysfunction of stem cells and/or their niche leads to disease state. The stem cells biology gets affected with age leading to a myeloid bias in differentiation of HSCs and increased incidence of myeloid leukemia. Present study was undertaken to enumerate VSELs, HSCs and MSCs and evaluate their response on D4 and D10 after chemotherapy with 5-Fluorouracil (5-FU) in young and aged mouse bone marrow. Stem cells were activated in response to 5-FU induced stress in an attempt to restore homeostasis. Although absolute numbers of VSELs and HSCs did not differ much between young and aged mice, their tendency to proliferate was higher on D4 in aged mice. However, ability to revert back to basal numbers and their differentiation was affected on D10 in aged marrow. Stem cells from aged bone marrow showed greater ability to form CFUs on D10 after 5-FU treatment. CD44 positive aged MSCs also showed increased proliferation on D10. Transplanting MSCs from young mice in 5-FU treated aged marrow helped improve hematopoiesis. The results suggest that no significant intrinsic changes occur as proliferative ability of stem cells remains unaffected but the niche gets affected with age leading to excessive self-renewal and compromised differentiation. This may explain increased incidence of leukemia with age.

中文翻译：

---

衰老和5-氟尿嘧啶治疗对骨髓干细胞动力学的影响。

骨髓的终生稳态由常驻干细胞维持，这些干细胞包括静止的非常小的胚胎样干细胞（VSEL）和受谱系限制的组织定型的“祖先”造血干细胞（HSC）。通过提供关键的旁分泌支持，提供间充质基质细胞（MSC）的利基调节VSEL / HSC的功能。干细胞和/或其生态位的任何功能障碍都会导致疾病状态。干细胞生物学随着年龄的增长而受到影响，导致HSCs分化过程中出现了髓样偏倚，并增加了髓样白血病的发生率。目前的研究是为了枚举VSEL，HSC和MSC并评估其在5-氟尿嘧啶（5-FU）化疗后在年轻和老年小鼠骨髓中对D4和D10的反应。干细胞被激活以响应5-FU诱导的压力，试图恢复体内平衡。尽管在年轻和老年小鼠之间，VSEL和HSC的绝对数量没有太大差异，但在老年小鼠的D4上，它们的增殖趋势更高。然而，恢复到基础数目的能力及其分化受到老年骨髓D10的影响。5-FU处理后，来自老年骨髓的干细胞显示出在D10上形成CFU的更大能力。CD44阳性衰老的MSC在D10上也显示出增加的增殖。从5-FU处理的老年小鼠中移植年轻小鼠的MSC有助于改善造血功能。结果表明，干细胞的增殖能力未受影响，但没有显着的内在变化发生，但是随着年龄的增长，利基受到影响，导致过度的自我更新和分化受损。