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几乎没有证据表明骨髓来源的细胞转分化为胰腺β细胞。

Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells.

作者信息

Choi J B, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H, Migita M, Shimada T, Kawamori R, Watada H

机构信息

Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.

出版信息

Diabetologia. 2003 Oct;46(10):1366-74. doi: 10.1007/s00125-003-1182-9. Epub 2003 Jul 26.

DOI:10.1007/s00125-003-1182-9
PMID:12898006
Abstract

AIMS/HYPOTHESIS: Bone marrow cells contain at least two distinct types of stem cells which are haematopoietic stem cells and mesenchymal stem cells. Both cells have the ability to differentiate into a variety of cell types derived from all three germ layers. Thus, bone marrow stem cells could possibly be used to generate new pancreatic beta cells for the treatment of diabetes. In this study, we investigated the feasibility of bone marrow-derived cells to differentiate into beta cells in pancreas.

METHODS

Using green fluorescent protein transgenic mice as donors, the distribution of haematogenous cells in the pancreas was studied after bone marrow transplantation.

RESULTS

In the pancreas of green fluorescent protein chimeric mice, green fluorescent protein-positive cells were found in the islets, but none of these cells expressed insulin. Previous data has suggested that tissue injury can recruit haematopoietic stem cells or their progeny to a non-haematopietic cell fate. Therefore, low-dose streptozotocin (30 or 50 mg/kg on five consecutive days) was injected into the mice 5 weeks after bone marrow transplantation, but no green fluorescent protein-positive cells expressing insulin were seen in the islets or around the ducts of the pancreas.

CONCLUSIONS/INTERPRETATION: Our data suggests that bone marrow-derived cells are a distinct cell population from islet cells and that transdifferentiation from bone marrow-derived cells to pancreatic beta cells is rarely observed.

摘要

目的/假设:骨髓细胞包含至少两种不同类型的干细胞,即造血干细胞和间充质干细胞。这两种细胞都有能力分化为源自所有三个胚层的多种细胞类型。因此,骨髓干细胞有可能用于生成新的胰岛β细胞以治疗糖尿病。在本研究中,我们调查了骨髓来源的细胞在胰腺中分化为β细胞的可行性。

方法

以绿色荧光蛋白转基因小鼠作为供体,在骨髓移植后研究造血细胞在胰腺中的分布。

结果

在绿色荧光蛋白嵌合小鼠的胰腺中,胰岛中发现了绿色荧光蛋白阳性细胞,但这些细胞均不表达胰岛素。先前的数据表明,组织损伤可促使造血干细胞或其后代转向非造血细胞命运。因此,在骨髓移植5周后给小鼠注射低剂量链脲佐菌素(连续5天,30或50mg/kg),但在胰岛或胰腺导管周围未见表达胰岛素的绿色荧光蛋白阳性细胞。

结论/解读:我们的数据表明,骨髓来源的细胞是与胰岛细胞不同的细胞群体,并且很少观察到骨髓来源的细胞向胰腺β细胞的转分化。

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Bone-marrow derived cells do not contribute to new beta-cells in the inflamed pancreas.骨髓来源的细胞不会对炎症胰腺中的新β细胞做出贡献。

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Int J Hematol. 2003 Jun;77(5):456-62. doi: 10.1007/BF02986613.
2
In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion.从骨髓中体内衍生出具有葡萄糖反应能力的胰腺内分泌细胞,且无细胞融合迹象。
J Clin Invest. 2003 Mar;111(6):843-50. doi: 10.1172/JCI16502.
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Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia.
Front Immunol. 2023 Jan 17;14:1084056. doi: 10.3389/fimmu.2023.1084056. eCollection 2023.
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2D and 3D cultured human umbilical cord-derived mesenchymal stem cell-conditioned medium has a dual effect in type 1 diabetes model in rats: immunomodulation and beta-cell regeneration.二维和三维培养的人脐带间充质干细胞条件培养基在大鼠1型糖尿病模型中具有双重作用:免疫调节和β细胞再生。
Inflamm Regen. 2022 Nov 30;42(1):55. doi: 10.1186/s41232-022-00241-7.
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Bone marrow mesenchymal stromal cells for diabetes therapy: touch, fuse, and fix?骨髓间充质基质细胞治疗糖尿病:接触、融合和修复?
Stem Cell Res Ther. 2022 Jul 26;13(1):348. doi: 10.1186/s13287-022-03028-2.
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Extraembryonic Mesenchymal Stromal/Stem Cells in Liver Diseases: A Critical Revision of Promising Advanced Therapy Medicinal Products.胚外间充质基质/干细胞在肝脏疾病中的应用:对有前途的先进治疗药物产品的批判性修订。
Cells. 2022 Mar 23;11(7):1074. doi: 10.3390/cells11071074.
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