Identification and characterization of a large source of primary mesenchymal stem cells tightly adhered to bone surfaces of human vertebral body marrow cavities.
Identification and characterization of a large source of primary mesenchymal stem cells tightly adhered to bone surfaces of human vertebral body marrow cavities.
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DOI：
10.1016/j.jcyt.2020.07.003
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发表时间：
2020-11
期刊：
影响因子：
4.5
通讯作者：
Woods EJ
中科院分区：
文献类型：
--
作者：
Johnstone BH;Miller HM;Beck MR;Gu D;Thirumala S;LaFontaine M;Brandacher G;Woods EJ
治疗性同种异体间充质基质细胞（MSC）目前正在临床试验中，以评估其在治疗许多不同疾病适应症中的有效性。广泛分布的最终商业化将需要进一步改进制造工艺，以经济地以足以满足预期需求的规模制造MSC。目前用于MSC制造的商品销售成本高的关键因素是需要从多个供体创建主细胞库，这导致大规模制造运行的可变性。因此，原代MSC的大型单一供体库的可用性将通过降低与制造相关的成本而极大地有益于细胞治疗市场。我们已经发现，具有MSC的所有特征的大量细胞群与椎体（VB）骨基质紧密相关，并且仅通过蛋白水解消化释放。在这里，我们证明了这些椎骨骨粘附（vBA）MSC具有所有国际细胞和基因治疗学会定义的特征（例如，塑料粘附、表面标志物表达和三系分化），因此我们将其称为vBA-MSC，以将该群体与通过抽吸或冲洗骨髓室回收的松散缔合的MSC区分开。用从3名死亡供体获得的vBA-MSC进行中试建库和扩增，证明仅从5 g消化的VB骨碎片可获得第1代平均2.9 × 108 ± 1.35 × 108 vBA-MSC的库大小。每个细胞库在总共9次传代中表现出稳健的增殖，群体倍增时间没有显著减少。来自每个供体的全部骨碎片（约300 g）经过4次有限扩增的理论总细胞产量为100万亿（1 × 1014）vBA-MSC，相当于平均70公斤受体在10 × 106个细胞/公斤下的105个剂量。因此，我们已经建立了一种新的和丰富的MSC来源，这将有利于细胞治疗市场，克服由于供体间变异性造成的制造和监管效率低下。
Therapeutic allogeneic mesenchymal stromal cells (MSCs) are currently in clinical trials to evaluate their effectiveness in treating many different disease indications. Eventual commercialization for broad distribution will require further improvements in manufacturing processes to economically manufacture MSCs at scales sufficient to satisfy projected demands. A key contributor to the present high cost of goods sold for MSC manufacturing is the need to create master cell banks from multiple donors, which leads to variability in large-scale manufacturing runs. Therefore, the availability of large single donor depots of primary MSCs would greatly benefit the cell therapy market by reducing costs associated with manufacturing. We have discovered that an abundant population of cells possessing all the hallmarks of MSCs is tightly associated with the vertebral body (VB) bone matrix and only liberated by proteolytic digestion. Here we demonstrate that these vertebral bone-adherent (vBA) MSCs possess all the International Society of Cell and Gene Therapy-defined characteristics (e.g., plastic adherence, surface marker expression and trilineage differentiation) of MSCs, and we have therefore termed them vBA-MSCs to distinguish this population from loosely associated MSCs recovered through aspiration or rinsing of the bone marrow compartment. Pilot banking and expansion were performed with vBA-MSCs obtained from 3 deceased donors, and it was demonstrated that bank sizes averaging 2.9 × 108 ± 1.35 × 108 vBA-MSCs at passage 1 were obtainable from only 5 g of digested VB bone fragments. Each bank of cells demonstrated robust proliferation through a total of 9 passages, without significant reduction in population doubling times. The theoretical total cell yield from the entire amount of bone fragments (approximately 300 g) from each donor with limited expansion through 4 passages is 100 trillion (1 × 1014) vBA-MSCs, equating to over 105 doses at 10 × 106 cells/kg for an average 70-kg recipient. Thus, we have established a novel and plentiful source of MSCs that will benefit the cell therapy market by overcoming manufacturing and regulatory inefficiencies due to donor-to-donor variability.
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影响因子：
6
作者：
Dykstra JA;Facile T;Patrick RJ;Francis KR;Milanovich S;Weimer JM;Kota DJ
通讯作者：
Kota DJ
影响因子：
4.5
作者：
Gorantla VS;Schneeberger S;Moore LR;Donnenberg VS;Zimmerlin L;Lee WP;Donnenberg AD
通讯作者：
Donnenberg AD
影响因子：
3.7
作者：
Beane OS;Fonseca VC;Cooper LL;Koren G;Darling EM
通讯作者：
Darling EM
DOI：
10.1016/j.bbrc.2014.01.084
发表时间：
2014-02-28
影响因子：
3.1
作者：
Eom, Young Woo;Oh, Ji-Eun;Shim, Kwang Yong
通讯作者：
Shim, Kwang Yong
影响因子：
--
作者：
Banfi, A;Bianchi, G;Quarto, R
通讯作者：
Quarto, R