Bioengineered Microtissue Models of the Human Bone Metastatic Microenvironment: A Novel In Vitro Theranostics Platform for Cancer Research

Abstract Human bone marrow cells cultured for 21 days in the presence of recombinant human interleukin-3 (IL-3) produced up to 28 times more colony-forming cells (CFC) than could be obtained from cultures stimulated with granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage CSF (GM-CSF). IL-3-cultured cells retained a multipotent response to IL-3 in colony assays but were restricted to formation of granulocyte colonies in G-CSF and granulocyte or macrophage colonies in GM-CSF. Culture of bone marrow cells in IL-3 also led to accumulation of large numbers of eosinophils and basophils. These data contrast with the effects of G-CSF, GM-CSF, and IL-3 in seven-day cultures. Here both GM-CSF and IL-3 amplified total CFC that had similar multipotential colony-forming capability in either factor. G-CSF, on the other hand, depleted IL-3-responsive colony-forming cells dramatically, apparently by causing these cells to mature into granulocytes. The data suggest that a large proportion of IL-3- responsive cells in human bone marrow express receptors for G-CSF and can respond to this factor, the majority becoming neutrophils. Furthermore, the CFC maintained for 21 days in IL-3 may be a functionally distinct population from that produced after seven days culture of bone marrow cells in either IL-3 or GM-CSF.

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Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02431-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Guping Mao ◽

Yiyang Xu ◽

Dianbo Long ◽

Hong Sun ◽

Hongyi Li ◽

...

Keyword(s):

Bone Marrow ◽

Mouse Model ◽

Chondrogenic Differentiation ◽

Cartilage Degradation ◽

Human Bone ◽

Human Bone Marrow ◽

Luciferase Reporter ◽

Gene And Protein Expression

Abstract Objectives Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Methods Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Results Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Conclusions Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA.

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New insights on CRISPR/Cas9-based therapy for breast Cancer

Genes and Environment ◽

10.1186/s41021-021-00188-0 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Hussein Sabit ◽

Shaimaa Abdel-Ghany ◽

Huseyin Tombuloglu ◽

Emre Cevik ◽

Amany Alqosaibi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Research ◽

Animal Models ◽

Human Cancer ◽

Step Process ◽

Cancer Initiation ◽

Malignant State ◽

Treat Breast Cancer

AbstractCRISPR/Cas9 has revolutionized genome-editing techniques in various biological fields including human cancer research. Cancer is a multi-step process that encompasses the accumulation of mutations that result in the hallmark of the malignant state. The goal of cancer research is to identify these mutations and correlate them with the underlying tumorigenic process. Using CRISPR/Cas9 tool, specific mutations responsible for cancer initiation and/or progression could be corrected at least in animal models as a first step towards translational applications. In the present article, we review various novel strategies that employed CRISPR/Cas9 to treat breast cancer in both in vitro and in vivo systems.

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