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Induction of CD45 expression on bone marrow-derived mesenchymal stem cells

Leukemia volume 20, pages 894–896 (2006)Cite this article

CD45 is the first prototypic receptor-like protein tyrosine phosphatase and is an essential regulator of signal transduction pathways in immune cells.1 CD45 is one of the most abundant leukocyte cell surface glycoproteins and is considered to be expressed exclusively upon cells of the hematopoietic system. The expression of CD45 on mesenchymal stem cells (MSCs), progenitor cells exhibiting multilineage differentiation capacity and being able to generate fibroblasts, osteoblasts, adipocytes and chondrocytes,2 has never been reported so far. Nevertheless, we had previously showed that expression of CD45 on bone marrow (BM)-derived and ex vivo-expanded MSCs can be detected on few specimens isolated from patients with hematological malignancies. The expression of CD45 was not only detected by flow cytometric analysis but was also demonstrated directly on ‘fibroblast-like’ cells by immunocytochemical study. The morphology of CD45+ MSCs is similar to that of CD45− MSCs and the multilineage differentiation potential of CD45+ MSCs is well preserved. However, the expression of CD45 was lost after prolonged ex vivo culture.3 These data suggest that MSCs can express CD45 under certain conditions. We therefore conducted this study to see whether modifying the condition of ex vivo culture can induce expression of CD45 on other BM-derived, CD45− MSCs. As the CD45+ MSCs were initially identified from BM of patients of multiple myeloma in our previous study and many cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), produced locally in the microenvironment by myeloma cells or other marrow components were well documented,4 we firstly added IL-1, IL-6 and TNF-α of different concentrations into the culture medium to simulate the ‘microenvironment’ of BM of myeloma. In addition to this, the presence of a specific protein is ultimately dependent on specific gene expression, and histone acetylation and DNA methylation are closely related to the activation or silencing of a gene. A typical example of this is the regulation of CD21 expression on the B lymphocyte.5 We subsequently added demethylating agent 5-aza-2′-deoxycytidine (AZA) and histone deacetylase inhibitor trichostatin acid (TSA) into the culture medium to see whether CD45 can be induced by changing epigenetic status or not.

The source of MSCs used in this study was the same as in our previous study.3 However, they were all initially CD45 negative on both immunocytochemical study and flow cytometric analysis. The isolation and ex vivo expansion of BM-derived MSCs were based on published protocol6 and the study was conducted under conditions approved by the Institutional Reviewing Board of China Medical University Hospital. To induce the expression of CD45 on MSCs, different concentrations of IL-1α (2, 10, 50 ng/ml), IL-6 (5, 25, 100 ng/ml), TNF-α (5, 25, 100 ng/ml; CytoLab Ltd, Rehovot, Israel), AZA (1 μ M) and TSA (0.1 μ M; Sigma, Munich, Germany) were added separately to the culture medium. As even minimal contamination of hematopoietic cells (‘stick’ to MSCs) may lead to false-positive CD45 expression of MSCs in flow cytometric analysis, in this study we used immunocytochemical staining to directly demonstrate whether CD45 can be seen on the ‘fibroblast’-like MSCs after modifying culture condition.

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Authors and Affiliations

  1. Department of Medical Research, Stem Cell Research Labaratory, China Medical University Hospital, Taichung, Taiwan

    S-P Yeh, J-G Chang, W-J Lo, Y-C Liaw, C-L Lin & C-C Lee

  2. Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    S-P Yeh & C-F Chiu

  3. China Medical University, Taichung, Taiwan

    S-P Yeh, J-G Chang & C-F Chiu

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  1. S-P Yeh
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Yeh, SP., Chang, JG., Lo, WJ. et al. Induction of CD45 expression on bone marrow-derived mesenchymal stem cells. Leukemia 20, 894–896 (2006). https://doi.org/10.1038/sj.leu.2404181

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