The Effect of Megakaryocytes and Platelets Derived from Human-Induced Pluripotent Stem Cells on Bone Formation.
The Effect of Megakaryocytes and Platelets Derived from Human-Induced Pluripotent Stem Cells on Bone Formation.
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DOI：
10.22603/ssrr.2020-0226
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发表时间：
2021
影响因子：
1.2
通讯作者：
Ohtori S
中科院分区：
文献类型：
--
作者：
Sato M;Shiga Y;Takayama N;Sone M;Kosaka K;Motegi I;Mizuki N;Inage K;Eguchi Y;Narita M;Orita S;Eto K;Ohtori S
富含血小板的血浆（PRP）作为一种可以促进骨形成的物质而受到关注。 PRP 中的生长因子在冷冻干燥后可以长期稳定。然而，PRP的效果并不一致，其在脊柱手术中对骨愈合的影响仍存在争议。源自人类诱导多能干细胞 (hiPSC) 的永生化巨核细胞系 (imMKCL) 已被开发用于生产大量稳定且具有临床功能的血小板。在本研究中，评估了冻干 hiPSC 衍生的 imMKCL 和血小板 (iPS-MK/Plts) 中存在的生长因子，并使用大鼠腰椎人工骨移植模型检查了它们促进骨形成的能力。 我们制备了冻干 iPS-MK/Plts，并通过酶联免疫吸附测定定量其生长因子。对8周龄雌性大鼠进行腰椎横突手术移植人工骨，分为两组：人工骨移植（对照）和人工骨移植加冻干iPS-MK/Plts（iPS组）。仅在左侧进行移植。手术后八周，我们捕获了计算机断层扫描图像，并比较了每只大鼠移植部位骨量的双边差异。我们还比较了两组之间的左侧/右侧骨体积比。 冻干的 iPS-MK/Plts 含有多种生长因子。虽然对照组移植侧骨量没有显着增加，但 iPS 组移植侧骨量显着增加，iPS 组平均左/右骨量比与对照组相比有所增加。但在 iPS 组中观察到的新骨在组织学上是正常的。 冻干 hiPSC 衍生的 MKCL 和血小板含有多种稳定的生长因子，具有促进新骨形成的潜力。
Platelet-rich plasma (PRP) is drawing attention as a substance that can promote bone formation. The growth factors present in PRP are stable for a long time after freeze-drying. However, the effects of PRP are inconsistent, and its effects on bone union in spinal surgery remain controversial. The immortalized megakaryocyte cell lines (imMKCLs) derived from human-induced pluripotent stem cells (hiPSCs) have been developed to produce numerous stable and clinically functional platelets. In this study, growth factors present in freeze-dried hiPSC-derived imMKCLs and platelets (iPS-MK/Plts) were evaluated, and their ability to promote bone formation was examined using a rat lumbar artificial bone grafting model. We prepared freeze-dried iPS-MK/Plts and quantified their growth factors by enzyme-linked immunosorbent assays. Surgical grafting of artificial bone to the lumbar transverse processes was performed in 8-week-old female rats, which were divided into two groups: artificial bone graft (control) and artificial bone graft plus freeze-dried iPS-MK/Plts (iPS group). Transplantation was performed only on the left side. Eight weeks after the surgery, we captured computed tomography images and compared bilateral differences in the bone volume of the graft site in each rat. We also compared the left side/right side bone volume ratio between the two groups. The freeze-dried iPS-MK/Plts contained numerous growth factors. While there was no significant increase in bone volume on the transplanted side than that on the non-grafted side in the control group, bone volume significantly increased on the transplanted side in the iPS group, as evidenced by augmented mean left/right bone volume ratio of the iPS group compared with that of the control group. But the new bone observed in the iPS group was histologically normal. Freeze-dried hiPSC-derived MKCLs and platelets contain several stable growth factors and have the potential for promoting new bone formation.
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