The Ely and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center of Reproductive Sciences, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, California 94143-0665, USA.
Transfusion. 2011 Nov;51 Suppl 4(Suppl 4):94S-105S. doi: 10.1111/j.1537-2995.2011.03372.x.
Hematopoietic stem cell (HSC) transplantation is an essential element of medical therapy, leading to cures of previously incurable hematological and nonhematological diseases. Many patients do not find matched donors in a timely manner, which has driven efforts to find alternative pools of transplantable HSCs. The use of umbilical cord blood (UCB) as a source of transplantable HSCs began more than two decades ago. However, the use of UCB as a reliable source of HSCs for transplantation still faces crucial challenges: the number of HSCs present in a unit of UCB is usually sufficient for younger children but not for adults, and the persistent delayed engraftment often seen can result in high rates of infection and mortality.
We propose a new approach to a solution of these problems: a potential increase of the limited number of UCB-HSCs available by harvesting HSCs contained in the placenta and the fetal chorionic membrane available at birth.
We investigated the presence of hematopoietic progenitors and HSCs in human placenta and chorion at different gestational ages. The characterization of these cells was performed by flow cytometry and immunolocalization, and their functional status was investigated by transplanting them into immunodeficient mice.
HSCs are present in extraembryonic tissues and could be banked in conjunction to the UCB-HSCs. This novel approach could have a large impact on the field of HSC banking and, more crucially, on the outcome of patients undergoing this treatment by greatly improving the use of life-saving hematopoietic transplants.
造血干细胞(HSC)移植是医学治疗的重要组成部分,可治愈以前无法治愈的血液系统和非血液系统疾病。许多患者无法及时找到匹配的供体,这促使人们努力寻找可移植 HSC 的替代来源。脐带血(UCB)作为可移植 HSC 的来源已使用了二十多年。然而,将 UCB 用作可移植 HSC 的可靠来源仍然面临着关键挑战:单位 UCB 中存在的 HSC 数量通常足以满足年幼儿童的需要,但不能满足成人的需要,并且经常出现的延迟植入会导致高感染率和死亡率。
我们提出了一种新的解决方案:通过收集出生时可用的胎盘和胎儿绒毛膜中的 HSC,来增加有限数量的 UCB-HSC。
我们研究了不同胎龄的人胎盘和绒毛膜中造血祖细胞和 HSC 的存在情况。通过流式细胞术和免疫定位对这些细胞进行了表征,并通过将其移植到免疫缺陷小鼠中来研究它们的功能状态。
HSC 存在于胚胎外组织中,可以与 UCB-HSC 一起储存。这种新方法可能会对 HSC 存储领域产生重大影响,更重要的是,通过大大改善挽救生命的造血移植的治疗效果,对接受这种治疗的患者的结果产生重大影响。