Amniotic stromal stem cell-loaded hydrogel repairs cardiac tissue in infarcted rat hearts via paracrine mediators


Posted: 2021-11-02 19:00:00
J Tissue Eng Regen Med . 2021 Nov 1. doi: 10.1002/term.3262. Online ahead of print. Affiliations Expand Affiliations 1 Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Canada. 2 Department of Mining and Materials Engineering, McGill University, Montreal, QC, H3A 0C5, Canada. 3 Human Islet Transplant Laboratory, Department of Surgery, McGill University Health Centre, Montréal, Québec, H3A 0G1, Canada. Item in Clipboard Kashif Khan et al. J Tissue Eng Regen Med. 2021. Show details Display options Display options Format J Tissue Eng Regen Med . 2021 Nov 1. doi: 10.1002/term.3262. Online ahead of print. Affiliations 1 Divisions of Cardiology and Cardiac Surgery, McGill University Health Centre, Montreal, Canada. 2 Department of Mining and Materials Engineering, McGill University, Montreal, QC, H3A 0C5, Canada. 3 Human Islet Transplant Laboratory, Department of Surgery, McGill University Health Centre, Montréal, Québec, H3A 0G1, Canada. Item in Clipboard CiteDisplay options Display options Format Abstract The use of stem cells to repair the heart after a myocardial infarction (MI) remains promising, yet clinical trials over the past 20 years suggest that cells fail to integrate into the native tissue, resulting in limited improvements in cardiac function. Here, we demonstrate the cardioprotective potential of a composite inserting human amniotic stromal mesenchymal stem cells (ASMCs) in a chitosan and hyaluronic acid (C/HA) based hydrogel in a rat MI model. Mechanical characterization of the C/HA platform indicated a swift elastic conversion at 40°C and a rapid sol-gel transition time at 37°C. Cell viability assay presented active and proliferating AMSCs in the C/HA. The ASMCs + C/HA injected composite significantly increased left ventricular ejection fraction, fractional shortening, and neovessel formation. The encapsulated AMSCs were abundantly detected in the infarcted myocardium 6 weeks post-administration and co-expressed cardiac proteins and notably proliferative markers. Proteomic profiling revealed that extracellular vesicles released from hypoxia preconditioned ASMCs contained proteins involved in cytoprotection, angiogenesis, cardiac differentiation and non-canonical Wnt-signaling. Independent activation of non-canonical Wnt-signaling pathways in ASMCs induced cardiogenesis. Despite a low injected cellular density at baseline, the encapsulated AMSCs were abundantly retained and increased cardiac function. Furthermore, the C/HA hydrogel provided an active milieu for the AMSCs to proliferate, co-express cardiac proteins, and induce new vessel formation. Hence, this novel composite of AMSCs + C/HA scaffold is a conceivable candidate that could restore cardiac function and reduce remodeling. This article is protected by copyright. All rights reserved. Keywords: Myocardial infarction; RT-PCR; Wnt-signaling; extracellular vesicles; mass spectrometry; mesenchymal stem cells. This article is protected by copyright. All rights reserved. LinkOut - more resources Miscellaneous [x] Cite Copy Format: Send To [x]

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バイオクイックニュース日本語版:エクソソーム特集

バイオクイックニュース日本語版
6月 20, 2019 バイオアソシエイツ

移植幹細胞由来エクソソームは心臓発作からの回復を助ける。移植細胞からの循環エキソソーム解析(液体生検)は医師が回復の程度を把握することを可能にする。

心筋の強化や他の疾患を治療する幹細胞療法は、ヒト臨床試験で有望視され始めている。 しかし、臨床成果の観察以外に、標的臓器内の移植細胞の有効性を評価するうえで再現性の欠如や使用期限、非侵襲的なツールの欠如は、幹細胞分野の進歩を遅らせてきた。 メリーランド大学医学部(UMSOM)、ペンシルバニア大学、およびエモリー大学の研究者らは、移植された幹細胞の有効性を追跡するのに血液検査が使用できると理論づけた。 彼らは、移植幹細胞からレシピエントの血液に分泌される エクソソーム と呼ばれる微小な細胞成分を分析した。…

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