人未成熟牙髓干细胞在获得性再生障碍性贫血小鼠模型中的治疗潜力。

Therapeutic Potential of Human Immature Dental Pulp Stem Cells Observed in Mouse Model for Acquired Aplastic Anemia.

机构信息

Genetics Laboratory, Instituto Butantan, São Paulo 05503-900, Brazil.

Cellavita Pesquisas Científicas Ltda., Valinhos 13271-650, Brazil.

出版信息

Cells. 2022 Jul 21;11(14):2252. doi: 10.3390/cells11142252.

Abstract

Aplastic anemia (AA) is a rare and serious disorder of hematopoietic stem cells (HSCs) that results in the loss of blood cells due to the failure of the bone marrow (BM). Although BM transplantation is used to treat AA, its use is limited by donor availability. In this sense, mesenchymal stem cells (MSCs) can offer a novel therapeutic approach for AA. This is because the MSCs contribute to the hematopoietic niche organization through their repopulating. In our study, we used the human immature dental pulp stem cell (hIDPSC), an MSC-like cell, to explore an alternative therapeutic approach for AA. For this, isogenic C57BL/6 mice were exposed to total body irradiation (TBI) to induce the AA. After 48 h of TBI, the mice were intraperitoneally treated with hIDPSC. The immunohistochemistry analyses confirmed that the hIDPSCs migrated and grafted in the mouse bone marrow (BM) and spleen, providing rapid support to hematopoiesis recovery compared to the group exposed to radiation, but not to those treated with the cells as well as the hematological parameters. Six months after the last hIDPSC transplantation, the BM showed long-term stable hematopoiesis. Our data highlight the therapeutic plasticity and hematoprotective role of hIDPSC for AA and potentially for other hematopoietic failures.

摘要

再生障碍性贫血(AA)是一种罕见且严重的造血干细胞(HSCs)疾病,导致骨髓(BM)失效而使血细胞丧失。虽然骨髓移植可用于治疗 AA,但由于供体可用性有限,其应用受到限制。从这个意义上说,间充质干细胞(MSCs)可为 AA 提供一种新的治疗方法。这是因为 MSCs 通过其再定植有助于造血龛组织的形成。在我们的研究中,我们使用人未成熟牙髓干细胞(hIDPSC),一种类似于 MSC 的细胞,来探索 AA 的替代治疗方法。为此,我们使同基因 C57BL/6 小鼠接受全身照射(TBI)以诱导 AA。TBI 后 48 小时,通过腹腔内注射 hIDPSC 对小鼠进行治疗。免疫组织化学分析证实 hIDPSC 迁移并移植到小鼠骨髓(BM)和脾脏中,与仅接受辐射的组相比,其对造血恢复提供了快速支持,但与接受细胞治疗的组以及血液学参数相比则没有。hIDPSC 移植后的最后 6 个月,BM 显示出长期稳定的造血。我们的数据强调了 hIDPSC 治疗 AA 以及潜在治疗其他造血衰竭的治疗可塑性和血液保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e69e/9315564/a7ede62b5180/cells-11-02252-g0A1.jpg

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