Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo

Cytotherapy ◽  
2011 ◽  
Vol 13 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Smruti M. Phadnis ◽  
Mugdha V. Joglekar ◽  
Maithili P. Dalvi ◽  
Sudhakar Muthyala ◽  
Prabha D. Nair ◽  
...  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guping Mao ◽  
Yiyang Xu ◽  
Dianbo Long ◽  
Hong Sun ◽  
Hongyi Li ◽  
...  

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.


1983 ◽  
Vol 1 (4) ◽  
Author(s):  
RichardH. Wheeler ◽  
DanielJ. Clauw ◽  
RonaldB. Natale ◽  
RaymondW. Ruddon

2012 ◽  
Vol 315 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Wei Zhu ◽  
Ling Huang ◽  
Yahong Li ◽  
Xu Zhang ◽  
Jianmei Gu ◽  
...  

2020 ◽  
Vol 168 (4) ◽  
pp. 561-565 ◽  
Author(s):  
V. N. Petrov ◽  
E. V. Isaeva ◽  
S. E. Ulyanenko ◽  
E. E. Beketov ◽  
E. M. Yatsenko ◽  
...  

2009 ◽  
Vol 34 (7) ◽  
pp. 1059-1068 ◽  
Author(s):  
Qiang Huang ◽  
Hui Zhang ◽  
Fu-xing Pei ◽  
Zhi-yu Chen ◽  
Guang-lin Wang ◽  
...  

2005 ◽  
Vol 116 (Supplement) ◽  
pp. 150-151
Author(s):  
Mahesh H. Mankani ◽  
Sergei Kuznetsov ◽  
Pamela Gehron Robey

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4322-4332 ◽  
Author(s):  
Malene Digmann Bjerregaard ◽  
Jesper Jurlander ◽  
Pia Klausen ◽  
Niels Borregaard ◽  
Jack Bernard Cowland

Abstract In vivo distribution of myeloid transcription factors during granulopoiesis was investigated by Northern and Western blotting in 3 neutrophil precursor populations from human bone marrow: immature (myeloblasts [MBs] and promyelocytes [PMs]); intermediate mature (myelocytes [MCs] and metamyelocytes [MMs]); and mature neutrophil cells (band cells [BCs] and segmented neutrophil cells [SCs]). Nonneutrophil cells were removed with magnetic-bead–coupled antibodies against CD2, CD3, CD14, CD19, CD56, CD61, glycophorin-A, and CD49d (BCs/SCs) before RNA and protein extraction. Polymorphonuclear neutrophils (PMNs) from peripheral blood depleted with anti-CD49d antibodies were also included. Expression of acute myeloid leukemia 1b (AML-1b), c-myb, GATA-1, and CCAAT/enhancer binding protein γ (C/EBP-γ) was seen primarily in MBs/PMs, and little expression was found in more mature cells. The level of C/EBP-α was constant in the bone marrow–derived cells and decreased in PMNs. C/EBP-ϵ was found primarily in MCs/MMs and was almost absent in more mature cells. Expression of C/EBP-β, C/EBP-δ, and C/EBP-ζ was observed from the MC/MM stage onward, with peak levels in the most mature cells. The amount of PU.1 increased throughout maturation whereas the level of Elf-1 reached a nadir in MCs/MMs The PU.1 coactivator c-jun and c-jun's dimerization partner c-fos were both detectable in MCs/MMs and increased in amount with maturity. CCAAT displacement protein (CDP) was found at comparable levels at all stages of differentiation. This demonstrates a highly individualized expression of the transcription factors, which can form the basis for the heterogeneous expression of granule proteins during granulopoiesis and cell cycle arrest in metamyelocytes.


Blood ◽  
1992 ◽  
Vol 79 (7) ◽  
pp. 1704-1711 ◽  
Author(s):  
S Kyoizumi ◽  
CM Baum ◽  
H Kaneshima ◽  
JM McCune ◽  
EJ Yee ◽  
...  

Abstract Human fetal bone fragments implanted in the immunodeficient C.B-17 scid/scid (SCID) mouse were shown to sustain active human hematopoiesis in vivo. Human progenitor cell activity was maintained for as long as 20 weeks after implantation and was associated with multilineage differentiation in the engrafted bone. Thus, the bone implants provided stem cells as well as the microenvironment requisite for their long- term maintenance and multilineage differentiation. Administration of human erythropoietin (Epo) stimulated human erythropoiesis in human bone implants. This animal model may facilitate direct analysis of a wide variety of physiologic and pathologic conditions of human bone marrow (BM) in vivo.


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