成体皮肤源性前体细胞雪旺细胞移植物在 Fischer 大鼠受损的脊髓中形成生长物。
Adult skin-derived precursor Schwann cell grafts form growths in the injured spinal cord of Fischer rats.
机构信息
Department of Physical Therapy, Faculty of Rehabilitation Medicine, and Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, T6G 2E1, Canada.
出版信息
Biomed Mater. 2018 Feb 20;13(3):034101. doi: 10.1088/1748-605X/aa95f8.
In this study, GFP skin-derived precursor Schwann cells (SKP-SCs) from adult rats were grafted into the injured spinal cord of immunosuppressed rats. Our goal was to improve grafted cell survival in the injured spinal cord, which is typically low. Cells were grafted in hyaluronan-methylcellulose hydrogel (HAMC) or hyaluronan-methylcellulose modified with laminin- and fibronectin-derived peptide sequences (eHAMC). The criteria for selection of hyaluronan was for its shear-thinning properties, making the hydrogel easy to inject, methylcellulose for its inverse thermal gelation, helping to keep grafted cells in situ, and fibronectin and laminin to improve cell attachment and, thus, prevent cell death due to dissociation from substrate molecules (i.e., anoikis). Post-mortem examination revealed large masses of GFP SKP-SCs in the spinal cords of rats that received cells in HAMC (5 out of n = 8) and eHAMC (6 out of n = 8). Cell transplantation in eHAMC caused significantly greater spinal lesions compared to lesion and eHAMC only control groups. A parallel study showed similar masses in the contused spinal cord of rats after transplantation of adult GFP SKP-SCs without a hydrogel or immunosuppression. These findings suggest that adult GFP SKP-SCs, cultured/transplanted under the conditions described here, have a capacity for uncontrolled proliferation. Growth-formation in pre-clinical research has also been documented after transplantation of: human induced pluripotent stem cell-derived neural stem cells (Itakura et al 2015 PLoS One 10 e0116413), embryonic stem cells and embryonic stem cell-derived neurons (Brederlau et al 2006 Stem Cells 24 1433-40; Dressel et al 2008 PLoS One 3 e2622), bone marrow derived mesenchymal stem cells (Jeong et al 2011 Circ. Res. 108 1340-47) and rat nerve-derived SCs following in vitro expansion for >11 passages (Funk et al 2007 Eur. J. Cell Biol. 86 207-19; Langford et al 1988 J. Neurocytology 17 521-9; Morrissey et al 1991 J. Neurosci. 11 2433-42). It is of upmost importance to define the precise culture/transplantation parameters for maintenance of normal cell function and safe and effective use of cell therapy.
在这项研究中，我们从成年大鼠中提取 GFP 皮肤源性前体细胞 Schwann 细胞（SKP-SCs），并将其移植到免疫抑制大鼠的损伤脊髓中。我们的目标是提高移植细胞在损伤脊髓中的存活率，因为这通常很低。我们将细胞移植到透明质酸-甲基纤维素水凝胶（HAMC）或经过层粘连蛋白和纤维连接蛋白衍生肽序列修饰的透明质酸-甲基纤维素（eHAMC）中。选择透明质酸的标准是其剪切变稀特性，这使得水凝胶易于注射；选择甲基纤维素是因为它具有逆温凝胶特性，有助于将移植细胞保留在原位；选择纤维连接蛋白和层粘连蛋白是为了改善细胞附着，从而防止细胞因与基质分子分离而死亡（即，失巢凋亡）。死后检查显示，在接受 HAMC（8 只大鼠中有 5 只）和 eHAMC（8 只大鼠中有 6 只）细胞移植的大鼠脊髓中存在大量 GFP SKP-SCs。与损伤和 eHAMC 仅对照组相比，eHAMC 中的细胞移植导致明显更大的脊髓损伤。一项平行研究表明，在没有水凝胶或免疫抑制的情况下，将成年 GFP SKP-SCs 移植到挫伤的大鼠脊髓中也会出现类似的大量细胞。这些发现表明，在本文所述条件下培养/移植的成年 GFP SKP-SCs 具有不受控制的增殖能力。在移植后也有文献记录了前临床研究中的生长形成：人诱导多能干细胞衍生的神经干细胞（Itakura 等人，2015 年 PLoS One 10 e0116413）、胚胎干细胞和胚胎干细胞衍生的神经元（Brederlau 等人，2006 年 Stem Cells 24 1433-40；Dressel 等人，2008 年 PLoS One 3 e2622）、骨髓来源的间充质干细胞（Jeong 等人，2011 年 Circ. Res. 108 1340-47）和大鼠神经源性 SCs 经过体外扩增超过 11 代（Funk 等人，2007 年 Eur. J. Cell Biol. 86 207-19；Langford 等人，1988 年 J. Neurocytology 17 521-9；Morrissey 等人，1991 年 J. Neurosci. 11 2433-42）。定义维持正常细胞功能和安全有效使用细胞治疗的确切培养/移植参数非常重要。
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