Takamiya Soichiro, Kawabori Masahito, Kitahashi Tsukasa, Nakamura Kentaro, Mizuno Yuki, Yasui Hironobu, Kuge Yuji, Tanimori Aki, Takamatsu Yasuyuki, Yuyama Kohei, Shichinohe Hideo, Fujimura Miki
Department of Neurosurgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Bioscience & Engineering Laboratory, FUJIFILM Corporation, Kanagawa, Japan.
Stem Cells Int. 2022 Jul 31;2022:8521922. doi: 10.1155/2022/8521922. eCollection 2022.
Due to the lack of effective therapies, stem cell transplantation is an anticipated treatment for chronic intracerebral hemorrhage (ICH), and higher cell survival and engraftment are considered to be the key for recovery. Mesenchymal stromal cells (MSCs) compounded with recombinant human collagen type I scaffolds (CellSaics) have a higher potential for cell survival and engraftment compared with solo-MSCs, and we investigated the validity of intracerebral transplantation of CellSaic in a chronic ICH model.
Rat CellSaics (rCellSaics) were produced by rat bone marrow-derived MSC (rBMSCs). The secretion potential of neurotrophic factors and the cell proliferation rate were compared under oxygen-glucose deprivation (OGD) conditions. rCellSaics, rBMSCs, or saline were transplanted into the hollow cavity of a rat chronic ICH model. Functional and histological analyses were evaluated, and single-photon emission computed tomography for benzodiazepine receptors was performed to monitor sequential changes in neuronal integrity. Furthermore, human CellSaics (hCellSaics) were transplanted into a chronic ICH model in immunodeficient rats. Antibodies neutralizing brain-derived neurotrophic factor (BDNF) were used to elucidate its mode of action.
rCellSaics demonstrated a higher secretion potential of trophic factors and showed better cell proliferation in the OGD condition. Animals receiving rCellSaics displayed better neurological recovery, higher intracerebral BDNF, and better cell engraftment; they also showed a tendency for less brain atrophy and higher benzodiazepine receptor preservation. hCellSaics also promoted significant functional recovery, which was reversed by BDNF neutralization.
Intracerebral transplantation of CellSaics enabled neurological recovery in a chronic ICH model and may be a good option for clinical application.
由于缺乏有效的治疗方法，干细胞移植被认为是慢性脑出血（ICH）的一种预期治疗手段，较高的细胞存活率和植入率被视为恢复的关键。与单独的间充质基质细胞（MSCs）相比，复合重组人I型胶原蛋白支架（CellSaics）的MSCs具有更高的细胞存活和植入潜力，我们在慢性ICH模型中研究了CellSaic脑内移植的有效性。
大鼠CellSaics（rCellSaics）由大鼠骨髓来源的MSC（rBMSCs）制备。在氧葡萄糖剥夺（OGD）条件下比较神经营养因子的分泌潜力和细胞增殖率。将rCellSaics、rBMSCs或生理盐水移植到大鼠慢性ICH模型的空洞中。进行功能和组织学分析，并进行苯二氮䓬受体的单光子发射计算机断层扫描以监测神经元完整性的连续变化。此外，将人CellSaics（hCellSaics）移植到免疫缺陷大鼠的慢性ICH模型中。使用中和脑源性神经营养因子（BDNF）的抗体来阐明其作用方式。
rCellSaics在OGD条件下表现出更高的营养因子分泌潜力和更好的细胞增殖。接受rCellSaics的动物表现出更好的神经功能恢复、更高的脑内BDNF水平和更好的细胞植入；它们还表现出脑萎缩较少和苯二氮䓬受体保留率较高的趋势。hCellSaics也促进了显著的功能恢复，BDNF中和可逆转这种恢复。
CellSaics脑内移植可使慢性ICH模型实现神经功能恢复，可能是临床应用的一个良好选择。
