Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #09-01, Singapore 138669, Singapore.
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, The Nanos, #09-01, Singapore 138669, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
Stem Cell Reports. 2017 Dec 12;9(6):1796-1812. doi: 10.1016/j.stemcr.2017.10.020. Epub 2017 Nov 22.
Current donor cell-dependent strategies can only produce limited "made-to-order" therapeutic natural killer (NK) cells for limited patients. To provide unlimited "off-the-shelf" NK cells that serve many recipients, we designed and demonstrated a holistic manufacturing scheme to mass-produce NK cells from induced pluripotent stem cells (iPSCs). Starting with a highly accessible human cell source, peripheral blood cells (PBCs), we derived a good manufacturing practice-compatible iPSC source, PBC-derived iPSCs (PBC-iPSCs) for this purpose. Through our original protocol that excludes CD34+ cell enrichment and spin embryoid body formation, high-purity functional and expandable NK cells were generated from PBC-iPSCs. Above all, most of these NK cells expressed no killer cell immunoglobulin-like receptors (KIRs), which renders them unrestricted by recipients' human leukocyte antigen genotypes. Hence, we have established a practical "from blood cell to stem cells and back with less (less KIRs)" strategy to generate abundant "universal" NK cells from PBC-iPSCs for a wide range of patients.
目前依赖供体细胞的策略只能为有限的患者生产有限数量的“定制”治疗性自然杀伤 (NK) 细胞。为了提供供许多受体使用的无限量“现成”NK 细胞，我们设计并展示了一种从诱导多能干细胞 (iPSC) 大规模生产 NK 细胞的整体制造方案。我们从易于获得的人类细胞来源外周血单个核细胞 (PBC) 出发，为此目的衍生出了一种符合良好生产规范 (GMP) 的 iPSC 来源，即 PBC 衍生的 iPSC (PBC-iPSC)。通过我们排除 CD34+细胞富集和旋转类胚体形成的原始方案，从 PBC-iPSC 中产生了高纯度功能和可扩增的 NK 细胞。最重要的是，这些 NK 细胞中的大多数不表达杀伤细胞免疫球蛋白样受体 (KIR)，这使它们不受受体人类白细胞抗原基因型的限制。因此，我们建立了一种实用的“从血细胞到干细胞再回来，减少 (减少 KIRs)”策略，从 PBC-iPSC 中产生大量“通用”NK 细胞，供广泛的患者使用。
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