Organ-specific extracellular matrix directs trans-differentiation of mesenchymal stem cells and formation of salivary gland-like organoids in vivo.
Organ-specific extracellular matrix directs trans-differentiation of mesenchymal stem cells and formation of salivary gland-like organoids in vivo.
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器官特异性的细胞外基质指导间充质干细胞的反差异，并在体内形成唾液腺样的类器官。
DOI：
10.1186/s13287-022-02993-y
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发表时间：
2022-07-15
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
目前对唾液腺（SG）功能减退的治疗是姑息性的，不能解决疾病的根本原因或进展。SG衍生的干细胞具有治疗SG功能减退的潜力，但它们的分离具有挑战性，特别是当组织因疾病或头颈癌辐射而受损时。在目前的研究中，我们测试的假设，即多能骨髓间充质干细胞（BM-MSCs）在大鼠模型中能够转分化为SG上皮细胞谱系时，诱导的天然SG特异性细胞外基质（SG-ECM），因此可能是一个可行的替代修复受损的SG。 将大鼠BM-MSC用脱细胞大鼠SG-ECM的匀浆在细胞悬浮液中处理1小时，然后在组织培养板中在生长培养基中培养7天。到第7天，培养物含有细胞聚集体和细胞单层。在解剖显微镜下手动选择细胞聚集体，转移到新的组织培养皿中，并在上皮细胞分化培养基中再培养7天。评价从单层分离的细胞聚集体和细胞的SG祖细胞和上皮细胞特异性标志物的表达、细胞形态和超微结构以及在体内形成SG样类器官的能力。结果表明，这种方法是非常有效的，并引导CD 133阳性BM-MSCs的亚群的SG上皮细胞谱系的转分化。这些细胞表达淀粉酶，紧密连接蛋白（Cldn 3和10），和标记SG腺泡（Aqp 5和Mist 1）和导管（Krt 14）细胞在转录本和蛋白质水平，产生细胞内分泌颗粒，其形态学上相同的那些发现在下颌下腺，并形成SG样类器官时，植入肾包膜在体内。这项研究的结果表明，使用自体骨髓间充质干细胞作为治疗SG功能减退和恢复这些患者的唾液产生的干细胞的丰富来源的可行性。
Current treatments for salivary gland (SG) hypofunction are palliative and do not address the underlying cause or progression of the disease. SG-derived stem cells have the potential to treat SG hypofunction, but their isolation is challenging, especially when the tissue has been damaged by disease or irradiation for head and neck cancer. In the current study, we test the hypothesis that multipotent bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model are capable of trans-differentiating to the SG epithelial cell lineage when induced by a native SG-specific extracellular matrix (SG-ECM) and thus may be a viable substitute for repairing damaged SGs. Rat BM-MSCs were treated with homogenates of decellularized rat SG-ECM for one hour in cell suspension and then cultured in tissue culture plates for 7 days in growth media. By day 7, the cultures contained cell aggregates and a cell monolayer. The cell aggregates were hand-selected under a dissecting microscope, transferred to a new tissue culture dish, and cultured for an additional 7 days in epithelial cell differentiation media. Cell aggregates and cells isolated from the monolayer were evaluated for expression of SG progenitor and epithelial cell specific markers, cell morphology and ultrastructure, and ability to form SG-like organoids in vivo. The results showed that this approach was very effective and guided the trans-differentiation of a subpopulation of CD133-positive BM-MSCs to the SG epithelial cell lineage. These cells expressed amylase, tight junction proteins (Cldn 3 and 10), and markers for SG acinar (Aqp5 and Mist 1) and ductal (Krt 14) cells at both the transcript and protein levels, produced intracellular secretory granules which were morphologically identical to those found in submandibular gland, and formed SG-like organoids when implanted in the renal capsule in vivo. The results of this study suggest the feasibility of using autologous BM-MSCs as an abundant source of stem cells for treating SG hypofunction and restoring the production of saliva in these patients.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
干细胞移植在辐照腺体中的干细胞移植后拯救唾液腺功能。
影响因子：
3.7
作者：
Lombaert, Isabelle M. A.;Brunsting, Jeanette F.;Wierenga, Pieter K.;Faber, Hette;Stokman, Monique A.;Kok, Tineke;Visser, Willy H.;Kampinga, Harm H.;de Haan, Gerald;Coppes, Robert P.
通讯作者：
Coppes, Robert P.
DOI：
10.1073/pnas.1601992113
发表时间：
2016-05-17
影响因子：
11.1
作者：
Lai, Zhennan;Yin, Hongen;Chiorini, John A.
通讯作者：
Chiorini, John A.
影响因子：
1.2
作者：
Calle, Elizabeth A.;Petersen, Thomas H.;Niklason, Laura E.
通讯作者：
Niklason, Laura E.
影响因子：
2.6
作者：
Jaskoll, T;Chen, HM;Melnick, M
通讯作者：
Melnick, M