Pub Date : 2022-06-02DOI: 10.1186/s13619-022-00121-y
Xing Qin, Juanjuan Fei, Yu Duan, Asli F Ceylan, Fuyang Zhang, Jun Ren
Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/-) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/- recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/- mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/- mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/- mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.
基于间充质干细胞(MSCs)的疗法在缺血性心脏病中显示出一定的前景,但其疗效可能会受到周围环境变化的影响。本研究利用Beclin1单倍体缺陷(BECN+/-)评估了自噬功能不足对心肌内间叶干细胞移植诱发心肌梗死疗效的影响。用细胞追踪器CM Dil标记来自C57BL/6小鼠的供体间充质干细胞,并在结扎左冠状动脉后将其送入野生型(WT)和BECN+/-受体小鼠心肌梗死区附近的左心室游离壁(MI-MSCs)。心肌梗死十天后,用超声心动图评估心肌功能。使用梗死邻近危险区的心肌细胞监测心肌细胞收缩力和胞内 Ca2+。使用荧光显微镜追踪间充质干细胞受体小鼠体内的 CM-Dil 标记细胞。利用凝集素、Masson 三色染色和 Western 印迹分析确定心肌细胞面积、瘢痕纤维化、细胞凋亡和炎症。心肌梗死会导致瘢痕纤维化、左心室腔扩张、缩短率下降、射血分数降低、心肌细胞缩短、最大缩短和再延长速度降低以及再延长时间延长。MI降低了细胞内Ca2+在电刺激下的上升和衰减,但并不影响静息细胞内Ca2+,而间叶干细胞在WT小鼠而非BECN+/-小鼠中可以调节这些变化。间充质干细胞进一步减轻了MI诱导的线粒体超微结构损伤、细胞凋亡、炎症以及WT而非BECN+/-小鼠梗死周围区域的自噬缺陷。总之,我们的研究结果表明,自噬不足抑制了间充质干细胞诱导的心脏保护作用,而这种保护作用与抑制细胞凋亡和炎症有关。
{"title":"Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction.","authors":"Xing Qin, Juanjuan Fei, Yu Duan, Asli F Ceylan, Fuyang Zhang, Jun Ren","doi":"10.1186/s13619-022-00121-y","DOIUrl":"10.1186/s13619-022-00121-y","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN<sup>+/-</sup>) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN<sup>+/-</sup> recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca<sup>2+</sup> were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN<sup>+/-</sup> mice. MI decreased intracellular Ca<sup>2+</sup> rise and decay in response to electrical stimuli without affecting resting intracellular Ca<sup>2+</sup>, which were reconciled by MSCs in WT but not BECN<sup>+/-</sup> mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN<sup>+/-</sup> mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.</p>","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"11 1","pages":"21"},"PeriodicalIF":4.0,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-05DOI: 10.1186/s13619-022-00118-7
Haonan Li, Xiaodan Wang, Yalong Wang, Mengxian Zhang, F. Hong, Hong Wang, Along Cui, Jianguo Zhao, W. Ji, Ye-Guang Chen
{"title":"Cross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium","authors":"Haonan Li, Xiaodan Wang, Yalong Wang, Mengxian Zhang, F. Hong, Hong Wang, Along Cui, Jianguo Zhao, W. Ji, Ye-Guang Chen","doi":"10.1186/s13619-022-00118-7","DOIUrl":"https://doi.org/10.1186/s13619-022-00118-7","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43438279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-05DOI: 10.1186/s13619-022-00120-z
Nevan Powers, Guo N. Huang
{"title":"Mending a broken heart with novel cardiogenic small molecules","authors":"Nevan Powers, Guo N. Huang","doi":"10.1186/s13619-022-00120-z","DOIUrl":"https://doi.org/10.1186/s13619-022-00120-z","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-02DOI: 10.1186/s13619-022-00116-9
Muchuan Wang, Ziquan Li, Sen Zhao, Zhifa Zheng, Yi‐peng Wang, G. Qiu, Zhihong Wu, N. Wu, T. Zhang, Siyi Cai
{"title":"The identification of PAX7 variants and a potential role of muscle development dysfunction in congenital scoliosis","authors":"Muchuan Wang, Ziquan Li, Sen Zhao, Zhifa Zheng, Yi‐peng Wang, G. Qiu, Zhihong Wu, N. Wu, T. Zhang, Siyi Cai","doi":"10.1186/s13619-022-00116-9","DOIUrl":"https://doi.org/10.1186/s13619-022-00116-9","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42974272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-01DOI: 10.1186/s13619-022-00113-y
Changmei Niu, Liyang Wang, Dongdong Ji, Mingjun Ren, Dongxu Ke, Qiang Fu, Kaile Zhang, Xi Yang
{"title":"Fabrication of SA/Gel/C scaffold with 3D bioprinting to generate micro-nano porosity structure for skin wound healing: a detailed animal in vivo study","authors":"Changmei Niu, Liyang Wang, Dongdong Ji, Mingjun Ren, Dongxu Ke, Qiang Fu, Kaile Zhang, Xi Yang","doi":"10.1186/s13619-022-00113-y","DOIUrl":"https://doi.org/10.1186/s13619-022-00113-y","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47841717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-20DOI: 10.1186/s13619-022-00108-9
D. Di Girolamo, S. Tajbakhsh
{"title":"Pathological features of tissues and cell populations during cancer cachexia","authors":"D. Di Girolamo, S. Tajbakhsh","doi":"10.1186/s13619-022-00108-9","DOIUrl":"https://doi.org/10.1186/s13619-022-00108-9","url":null,"abstract":"","PeriodicalId":9811,"journal":{"name":"Cell Regeneration","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65859575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}