Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice.
Pre-clinical development of a cryopreservable megakaryocytic cell product capable of sustained platelet production in mice.
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能够在小鼠体内持续产生血小板的可冷冻巨核细胞产品的临床前开发。
DOI：
10.1111/trf.15546
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发表时间：
2019
期刊：
影响因子：
2.9
通讯作者：
Iancu-Rubin,Camelia
中科院分区：
文献类型：
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作者：
Patel,Ami;Clementelli,CaraMarie;Jarocha,Danuta;Mosoyan,Gohar;Else,Cindy;Kintali,Manisha;Fong,Helen;Tong,Jay;Gordon,Ronald;Gillespie,Virginia;Keyzner,Alla;Poncz,Mortimer;Hoffman,Ronald;Iancu-Rubin,Camelia
背景：血小板（PLT）输注是治疗血小板减少症患者最有效的方法。由于依赖志愿献血者、保质期短、有污染病原体的风险以及同种异体免疫，对PLT输血产品的需求不断增长，但供应有限，这使情况更加复杂。这项研究提供了临床前证据，证明第三方的、可低温保存的PLT生成细胞来源有可能补充目前可用的PLT输血产品。研究设计与方法将脐带血（UCB）单位的scd34 +造血干细胞/祖细胞用于简单高效的培养系统中，以产生由不同发育阶段的巨核细胞（mk）组成的细胞产物。由此产生的培养物在冷冻保存前后分别在体外和体内进行评价。结果制备的巨核细胞产物可以在不改变其表型和功能的情况下进行低温保存。将这种产品（无论是新鲜的还是冷冻保存的）输注到免疫缺陷小鼠体内，可以在输注后一周内观察到产生功能性的人PLT，并持续8周，比输注传统PLT输注产品观察到的时间长几个数量级。持续的人类PLT移植伴随着受体小鼠骨髓（BM）、脾脏和肺中人类细胞的强劲存在。结论：这是一项原理验证研究，证明了一种可低温保存的巨核细胞产品的产生，该产品可在体内释放功能性plt。目前正在进行这种产品的临床开发，用于治疗血液系统恶性肿瘤患者的血小板减少症。
BACKGROUNDPlatelet (PLT) transfusions are the most effective treatments for patients with thrombocytopenia. The growing demand for PLT transfusion products is compounded by a limited supply due to dependency on volunteer donors, a short shelf‐life, risk of contaminating pathogens, and alloimmunization. This study provides preclinical evidence that a third‐party, cryopreservable source of PLT‐generating cells has the potential to complement presently available PLT transfusion products.STUDY DESIGN AND METHODSCD34+ hematopoietic stem/progenitor cells derived from umbilical cord blood (UCB) units were used in a simple and efficient culture system to generate a cell product consisting of megakaryocytes (MKs) at different stages of development. The cultures thus generated were evaluated ex vivo and in vivo before and after cryopreservation.RESULTSWe generated a megakaryocytic cell product that can be cryopreserved without altering its phenotypical and functional capabilities. The infusion of such a product, either fresh or cryopreserved, into immune‐deficient mice led to production of functional human PLTs which were observed within a week after infusion and persisted for 8 weeks, orders of magnitude longer than that observed after the infusion of traditional PLT transfusion products. The sustained human PLT engraftment was accompanied by a robust presence of human cells in the bone marrow (BM), spleen, and lungs of recipient mice.CONCLUSIONThis is a proof‐of‐principle study demonstrating the creation of a cryopreservable megakaryocytic cell product which releases functional PLTs in vivo. Clinical development of such a product is currently being pursued for the treatment of thrombocytopenia in patients with hematological malignancies.