McKinney-Freeman Shannon, Goodell Margaret A
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
Exp Hematol. 2004 Sep;32(9):868-76. doi: 10.1016/j.exphem.2004.06.010.
Hematopoietic stem cells (HSC), normally resident in bone marrow, can be detected in the murine and human circulation. It is thought that HSC move in and out of bone marrow daily and that returning HSC are generally equivalent to their bone marrow counterparts in phenotype and function. However, large numbers of mononuclear blood cells are required to rescue animals from lethal irradiation, indicating either that the prevalence of circulating HSC is low, or they are inherently deficient in their repopulating ability. Accordingly, recent data suggest that circulating HSC may be unable to stably engraft WBM under homeostatic conditions. The purpose of this study was to explore these dynamics in detail using parabiosis and bone marrow transplantation.
The WBM and skeletal muscle HSC stem cell compartments of parabiosed CD45 congenic mice were analyzed functionally (via bone marrow transplantation) and phenotypically (via flow cytometry) for circulating stem cells at specific time points postparabiosis and after surgical separation.
Surprisingly, we find that stem cells trafficking out of bone marrow and into the circulation do not stably return to bone marrow, although long-lived lymphoid precursors do stably re-engraft. Circulating HSC do, however, take up residence in skeletal muscle, wherein they account for HSC activity.
Circulating HSC are not in flux with the bone marrow HSC and can persist in peripheral tissues.
造血干细胞（HSC）通常存在于骨髓中，但在小鼠和人类循环系统中也可检测到。据认为，HSC 每日进出骨髓，且返回骨髓的 HSC 在表型和功能上通常与其骨髓对应细胞相当。然而，需要大量单核血细胞才能使动物从致死性辐射中获救，这表明要么循环 HSC 的比例较低，要么它们的再增殖能力本身存在缺陷。因此，最近的数据表明，在稳态条件下，循环 HSC 可能无法稳定植入全骨髓（WBM）。本研究的目的是利用联体共生和骨髓移植详细探究这些动态变化。
对联体共生的 CD45 同基因小鼠的全骨髓和骨骼肌 HSC 干细胞区室在联体共生后及手术分离后的特定时间点进行功能分析（通过骨髓移植）和表型分析（通过流式细胞术），以检测循环干细胞。
令人惊讶的是，我们发现从骨髓进入循环的干细胞不会稳定返回骨髓，尽管长寿淋巴细胞前体细胞确实能稳定再植入。然而，循环 HSC 确实会在骨骼肌中定居，在那里它们构成 HSC 活性。
循环 HSC 与骨髓 HSC 不存在动态变化，且可在外周组织中持续存在。
