A Single-center, Prospective Trial of the Safety and Efficacy of UCMSC-Exo in Consolidation Chemotherapy-induced Myelosuppression in Patients With Acute Myeloid Leukemia After Achieving Complete Remission

The purpose of the study is to explore the safety and efficacy of UCMSC-Exo in consolidation chemotherapy-induced myelosuppression in patients with acute myeloid leukemia after achieving complete remission.

开始日期2024-03-01

申办/合作机构

武汉协和医院

100 项与 Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital) 相关的临床结果

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100 项与 Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital) 相关的转化医学

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100 项与 Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital) 相关的专利（医药）

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项与 Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital) 相关的文献（医药）

2024-05-01·Journal of Orthopaedic Translation

Exosomes from umbilical cord mesenchymal stem cells ameliorate intervertebral disc degeneration via repairing mitochondrial dysfunction

Article

作者: Liang, Xiao ; Zhang, Zifang ; Zhao, Siqi ; Gao, Longfei ; Yang, Tao ; Meng, Chunyang ; Zhang, Bin ; Gao, Xu ; Li, Dongru ; Wang, Yexin ; Zhu, Zhiguo ; Bai, Luyue ; Li, Yanpeng ; Jia, Shu ; Gao, Sheng ; Chen, Shang

BackgroundReactive oxygen species (ROS), predominantly generated by mitochondria, play a crucial role in the pathogenesis of intervertebral disc degeneration (IVDD). Reduction of ROS levels may be an effective strategy to delay IVDD. In this study, we assessed whether umbilical cord mesenchymal stem cell-exosomes (UCMSC-exos) can be used to treat IVDD by suppressing ROS production caused by mitochondrial dysfunction.Materials and methodsHuman UCMSC-exos were isolated and identified. Nucleus pulposus cells (NPCs) were stimulated with H₂O₂ in the presence or absence of exosomes. Then, 4D label free quantitative (4D-LFQ) proteomics were used to analyze the differentially expressed (DE) proteins. Mitochondrial membrane potential (MMP), mitochondrial ROS and protein levels were determined via immunofluorescence staining, flow cytometry and western blotting respectively. Additionally, high-throughput sequencing was performed to identify the DE miRNAs in NPCs. Finally, therapeutic effects of UCMSC-exos were investigated in a puncture-induced IVDD rat model. Degenerative grades of rat IVDs were assessed using magnetic resonance imaging and histochemical staining.ResultsUCMSC-exos effectively improved the viability of NPCs and restored the expression of the extracellular matrix (ECM) proteins, collagen type II alpha-1 (COL2A1) and matrix metalloproteinase-13 induced by H₂O₂. Additionally, UCMSC-exos not only reduced the total intracellular ROS and mitochondrial superoxide levels, but also increased MMP in pathological NPCs. 4D-LFQ proteomics and western blotting further revealed that UCMSC-exos up-regulated the levels of the mitochondrial protein, mitochondrial transcription factor A (TFAM), in H₂O₂-induced NPCs. High-throughput sequencing and qRT-PCR uncovered that UCMSC-exos down-regulated the levels of miR-194-5p, a potential negative regulator of TFAM, induced by H₂O₂. Finally, in vivo results showed that UCMSC-exos injection improved the histopathological structure and enhanced the expression levels of COL2A1 and TFAM in the rat IVDD model.ConclusionsOur findings suggest that UCMSC-exos promote ECM synthesis, relieve mitochondrial oxidative stress, and attenuate mitochondrial dysfunction in vitro and in vivo, thereby effectively treating IVDD.The translational potential of this articleThis study provides solid experimental data support for the therapeutic effects of UCMSC-exos on IVDD, suggesting that UCMSC-exos will be a promising nanotherapy for IVDD.

2024-01-01·Biomaterials Research

The Inhibition of Fibrosis and Inflammation in Obstructive Kidney Injury via the miR-122-5p/SOX2 Axis Using USC-Exos

Article

作者: Liu, Hengchen ; Li, Xiangqi ; Jiang, Zhitao ; Shi, Manyu ; Li, Zhaozhu ; Zhao, Zheng ; Li, Zhou ; Guo, Yujun ; Yang, Shulong ; Zhang, Tingting ; Zhang, Mingzhao ; Lu, Wenjun

Background:Fibrosis and inflammation due to ureteropelvic junction obstruction substantially contributes to poor renal function. Urine-derived stem-cell-derived exosomes (USC-Exos) have therapeutic effects through paracrine.Methods:In vitro, the effects of USC-Exos on the biological functions of HK-2 and human umbilical vein endothelial cells were tested. Cell inflammation and fibrosis were induced by transforming growth factor-β1 and interleukin-1β, and their anti-inflammatory and antifibrotic effects were observed after exogenous addition of USC-Exos. Through high-throughput sequencing of microRNA in USC-Exos, the pathways and key microRNAs were selected. Then, the antifibrotic and anti-inflammatory effects of exosomal miR-122-5p and target genes were verified. The role of the miR-122-5p/SOX2 axis in anti-inflammatory and antifibrotic effects was verified. In vivo, a rabbit model of partial unilateral ureteral obstruction (PUUO) was established. Magnetic resonance imaging recorded the volume of the renal pelvis after modeling, and renal tissue was pathologically analyzed.Results:We examined the role of USC-Exos and their miR-122-5p content in obstructive kidney injury. These Exos exhibit antifibrotic and anti-inflammatory activities. SOX2 is the hub gene in PUUO and negatively related to renal function. We confirmed the binding relationship between miR-122-5p and SOX2. The anti-inflammatory and antifibrotic effects of miR-122-5p were inhibited, indicating that miR-122-5p has anti-inflammatory and antifibrotic effects by inhibiting SOX2 expression. In vivo, the PUUO group showed typical obstructive kidney injury after modeling. After USC-Exo treatment, the shape of the renal pelvis shown a remarkable improvement, and inflammation and fibrosis decreased.Conclusions:We confirmed that miR-122-5p from USC-Exos targeting SOX2 is a new molecular target for postoperative recovery treatment of obstructive kidney injury.

International Journal of Molecular Sciences

Cinnamaldehyde-Treated Bone Marrow Mesenchymal-Stem-Cell-Derived Exosomes via Aqueous Two-Phase System Attenuate IL-1β-Induced Inflammation and Catabolism via Modulation of Proinflammatory Signaling Pathways

Article

作者: Kang, Ju Yeon ; Kim, Hyung Keun ; Lee, Seok Cheol ; Sankaranarayanan, Jaishree ; Seon, Jong Keun ; Kuppa, Sree Samanvitha

Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1β (IL-1β) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1β on chondrocytes. We stimulated chondrocytes with IL-1β to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1β on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1β on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.

100 项与 Umbilical Cord Derived Mesenchymal Stem Cells Exosomes(Wuhan Union Hospital) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床1期	-	武汉协和医院	2024-03-01
贫血	临床1期	-	武汉协和医院	2024-03-01
出血	临床1期	-	武汉协和医院	2024-03-01
感染	临床1期	-	武汉协和医院	2024-03-01
中性粒细胞减少	临床1期	-	武汉协和医院	2024-03-01
血小板减少症	临床1期	-	武汉协和医院	2024-03-01