{"title":"Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects.","authors":"Dongdong Li, Haolin Liu, Chaochao Li, Yanjun Guan, Xing Xiong, Ruichao He, Zhibo Jia, Lijing Liang, Jinjuan Zhao, Xinyu Miao, Yu Wang, Jiang Peng","doi":"10.1177/09636897241291278","DOIUrl":"10.1177/09636897241291278","url":null,"abstract":"<p><p>Autologous nerve transplantation (ANT) remains the gold standard for treating nerve defects. However, its efficacy in nerve repair still requires improvement. Mitochondrial dysfunction resulting from nerve injury may be a significant factor limiting nerve function restoration. This study investigated the impact of supplementing exogenous mitochondria (EM) in ANT and explored its effect on the efficacy of ANT in nerve repair. SD rats were used to prepare a model of a 10 mm sciatic nerve defect repaired by ANT (Auto group) and a model of ANT supplemented with EM (Mito group). At 12 weeks post-operation, functional, neurophysiological, and histological evaluations of the target organ revealed that the Mito group exhibited significantly better outcomes compared with the Auto group, with statistically significant differences (<i>P</i> < 0.05). <i>In vitro</i> experiments demonstrated that EM could be endocytosed by Schwann cells (SCs) and dorsal root ganglion neurons (DRGs) when co-cultured. After endocytosis by SCs, immunofluorescence staining of autophagy marker LC3II and mitochondrial marker Tomm20, as well as adenoviral fluorescence labeling of lysosomes and mitochondria, revealed that EM could promote autophagy in SCs. CCK8 and EDU assays also indicated that EM significantly promoted SCs proliferation and viability. After endocytosis by DRGs, EM could accelerate axonal growth rate. A sciatic nerve defect repair model prepared using Thy1-YFP-16 mice also revealed that EM could accelerate axonal growth <i>in vivo</i>, with statistically significant results (<i>P</i> < 0.05). This study suggests that EM enhances autophagy in SCs, promotes SCs proliferation and viability, and increases the axonal growth rate, thereby improving the efficacy of ANT. This research provides a novel therapeutic strategy for enhancing the efficacy of ANT in nerve repair.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241291278"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advancing Cell Transplantation Research with Integrity and Rigor.","authors":"Ying Lou","doi":"10.1177/09636897241309996","DOIUrl":"https://doi.org/10.1177/09636897241309996","url":null,"abstract":"","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241309996"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ke Hu, Shengkai Jin, Ke Yue, Huan Wang, Chunhui Cai, Qian Liu, Jianrong Guo, Qiujuan Liang, Yu Tian, Zhengliang Gao
{"title":"A Reversible Neural Stem Cell Quiescence and Activation Culture System for Metabolic Study.","authors":"Ke Hu, Shengkai Jin, Ke Yue, Huan Wang, Chunhui Cai, Qian Liu, Jianrong Guo, Qiujuan Liang, Yu Tian, Zhengliang Gao","doi":"10.1177/09636897241259723","DOIUrl":"10.1177/09636897241259723","url":null,"abstract":"<p><p>Stem cells <i>in vivo</i> can transit between quiescence and activation, two metabolically distinct states. It is increasingly appreciated that cell metabolism assumes profound roles in stem cell maintenance and tissue homeostasis. However, the lack of suitable models greatly hinders our understanding of the metabolic control of stem cell quiescence and activation. In the present study, we have utilized classical signaling pathways and developed a cell culture system to model reversible NSC quiescence and activation. Unlike activated ones, quiescent NSCs manifested distinct morphology characteristics, cell proliferation, and cell cycle properties but retained the same cell proliferation and differentiation potentials once reactivated. Further transcriptomic analysis revealed that extensive metabolic differences existed between quiescent and activated NSCs. Subsequent experimentations confirmed that NSC quiescence and activation transition was accompanied by a dramatic yet coordinated and dynamic shift in RNA metabolism, protein synthesis, and mitochondrial and autophagy activity. The present work not only showcases the broad utilities of this powerful <i>in vitro</i> NSC quiescence and activation culture system but also provides timely insights for the field and warrants further investigations.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241259723"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11179495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiunn-Jye Sheu, Jui-Ning Yeh, Pei-Hsun Sung, John Y Chiang, Yi-Ling Chen, Yi-Ting Wang, Hon-Kan Yip, Jun Guo
{"title":"ITRI Biofilm Prevented Thoracic Adhesion in Pigs That Received Myocardial Ischemic Induction Treated by Myocardial Implantation of EPCs and ECSW Treatment.","authors":"Jiunn-Jye Sheu, Jui-Ning Yeh, Pei-Hsun Sung, John Y Chiang, Yi-Ling Chen, Yi-Ting Wang, Hon-Kan Yip, Jun Guo","doi":"10.1177/09636897241253144","DOIUrl":"10.1177/09636897241253144","url":null,"abstract":"<p><p>This study tested the hypothesis that ITRI Biofilm prevents adhesion of the chest cavity. Combined extracorporeal shock wave (ECSW) + bone marrow-derived autologous endothelial progenitor cell (EPC) therapy was superior to monotherapy for improving heart function (left ventricular ejection fraction [LVEF]) in minipigs with ischemic cardiomyopathy (IC) induced by an ameroid constrictor applied to the mid-left anterior descending artery. The minipigs (<i>n</i> = 30) were equally designed into group 1 (sham-operated control), group 2 (IC), group 3 (IC + EPCs/by directly implanted into the left ventricular [LV] myocardium; 3 [+]/3[-] ITRI Biofilm), group 4 (IC + ECSW; 3 [+]/[3] - ITRI Biofilm), and group 5 (IC + EPCs-ECSW; 3 [+]/[3] - ITRI Biofilm). EPC/ECSW therapy was administered by day 90, and the animals were euthanized, followed by heart harvesting by day 180. <i>In vitro</i> studies demonstrated that cell viability/angiogenesis/cell migratory abilities/mitochondrial concentrations were upregulated in EPCs treated with ECSW compared with those in EPCs only (all <i>P</i>s < 0.001). The LVEF was highest in group 1/lowest in group 2/significantly higher in group 5 than in groups 3/4 (all <i>P</i>s < 0.0001) by day 180, but there was no difference in groups 3/4. The adhesion score was remarkably lower in patients who received ITRI Biofilm treatment than in those who did not (all <i>P</i>s <0.01). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptotic (mitochondrial-Bax/caspase3/PARP)/fibrotic (TGF-β/Smad3)/DNA/mitochondria-damaged (γ-H2AX/cytosolic-cytochrome-C/p-DRP1), and heart failure/pressure-overload (BNP [brain natriuretic peptide]/β-MHC [beta myosin heavy chain]) biomarkers displayed a contradictory manner of LVEF among the groups (all <i>P</i>s < 0.0001). The protein expression of endothelial biomarkers (CD31/vWF)/small-vessel density revealed a similar LVEF within the groups (all <i>P</i>s < 0.0001). ITRI Biofilm treatment prevented chest cavity adhesion and was superior in restoring IC-related LV dysfunction when combined with EPC/ECSW therapy compared with EPC/ECSW therapy alone.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241253144"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huiru Wang, Kai Chen, Lu Zong, Xin Zhao, Jingxin Wang, Shiwei Fan, Bing Shen, Shengxia Zheng
{"title":"MALAT1/miR-7-5p/TCF4 Axis Regulating Menstrual Blood Mesenchymal Stem Cells Improve Thin Endometrium Fertility by the Wnt Signaling Pathway.","authors":"Huiru Wang, Kai Chen, Lu Zong, Xin Zhao, Jingxin Wang, Shiwei Fan, Bing Shen, Shengxia Zheng","doi":"10.1177/09636897241259552","DOIUrl":"10.1177/09636897241259552","url":null,"abstract":"<p><p>Thin endometrium (TE) is a significant factor contributing to fertility challenges, and addressing this condition remains a central challenge in reproductive medicine. Menstrual blood-derived mesenchymal stem cells (MenSCs) play a crucial role in tissue repair and regeneration, including that of TE. The Wnt signaling pathway, which is highly conserved and prevalent in eukaryotes, is essential for cell proliferation, tissue development, and reproductive functions. MALAT1 is implicated in various transcriptional and molecular functions, including cell proliferation and metastasis. However, the combined effects of the Wnt signaling pathway and the long non-coding RNA (lncRNA) MALAT1 on the regulation of MenSCs' regenerative capabilities in tissue engineering have not yet been explored. To elucidate the regulatory mechanism of MALAT1 in TE, we analyzed its expression levels in normal endometrium and TE tissues, finding that low expression of MALAT1 was associated with poor clinical prognosis. In addition, we conducted both <i>in vitro</i> and <i>in vivo</i> functional assays to examine the role of the MALAT1/miR-7-5p/TCF4 axis in cell proliferation and migration. Techniques such as dual-luciferase reporter assay, fluorescent <i>in situ</i> hybridization, and immunoblot experiments were utilized to clarify the molecular mechanism. To corroborate these findings, we established a TE model and conducted pregnancy experiments, demonstrating a strong association between MALAT1 expression and endometrial fertility. In conclusion, our comprehensive study provides strong evidence supporting that lncRNA MALAT1 modulates TCF4 expression in the Wnt signaling pathway through interaction with miR-7-5p, thus enhancing MenSCs-mediated improvement of TE and improving fertility.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241259552"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11162126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna French, Jennifer Hollister-Lock, Brooke A Sullivan, Eline Stas, Albert J Hwa, Gordon C Weir, Susan Bonner-Weir
{"title":"Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel.","authors":"Anna French, Jennifer Hollister-Lock, Brooke A Sullivan, Eline Stas, Albert J Hwa, Gordon C Weir, Susan Bonner-Weir","doi":"10.1177/09636897241283728","DOIUrl":"10.1177/09636897241283728","url":null,"abstract":"<p><p>Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell-derived beta-like cells. Efforts have been underway to find an alternative transplant site that will foster better islet cell survival and function. Although conceptually attractive, the subcutaneous (SC) site has yielded disappointing results, in spite of some improvements resulting from more attention paid to vascularization and differentiation factors, including collagen. We developed a method to transplant rat islets in a disk of type 1 collagen gel and found improved efficacy of these transplants. Survival of islets following transplantation (tx) was determined by comparing insulin content of the graft to that of the pre-transplant islets from the same isolation. At 14 days after transplantation, grafts of the disks had more than double the recovered insulin than islets transplanted in ungelled collagen. SC grafts of disks had similar insulin content to grafts in a kidney site and in epididymal fat pads. <i>In vivo</i> disks underwent contraction to 10% of initial volume within 24 h but the islets remained healthy and well distributed. Whole mount imaging showed that residual donor vascular cells within the islets expanded and connected to ingrowing host blood vessels. Islets (400 rat islet equivalents (IEQ)) in the collagen disks transplanted into an SC site of NOD scid IL2R gammanull (NSG) mice reversed streptozotocin (STZ)-induced diabetes within 10 days as effectively as transplants in the kidney site. Thus, a simple change of placing islets into a gel of collagen 1 prior to transplantation allowed a prompt reversal of STZ-induced diabetes using SC site.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241283728"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muyun Liu, Wanglong Chu, Tao Guo, Xiuping Zeng, Yan Shangguan, Fangtao He, Xiao Liang
{"title":"Challenges of Cell Counting in Cell Therapy Products.","authors":"Muyun Liu, Wanglong Chu, Tao Guo, Xiuping Zeng, Yan Shangguan, Fangtao He, Xiao Liang","doi":"10.1177/09636897241293628","DOIUrl":"10.1177/09636897241293628","url":null,"abstract":"<p><p>Cell counting is a common and fundamental cell measurement technique that plays a crucial role in the development and quality control of cell therapy products. However, accurate and reliable cell counting can be challenging owing to the complexity of cell preparations, diverse counting purposes, and various counting methods. This review summarizes the challenges encountered in cell counting for cell therapy products and provides strategies to improve the cell counting accuracy, thereby guiding the counting process and ensuring the quality of cell therapy products.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241293628"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cross Talk Between Cells and the Current Bioceramics in Bone Regeneration: A Comprehensive Review.","authors":"Danial Khayatan, Asal Bagherzadeh Oskouei, Mostafa Alam, Meysam Mohammadikhah, Ashkan Badkoobeh, Mohsen Golkar, Kamyar Abbasi, Shahryar Karami, Reza Sayyad Soufdoost, Lotfollah Kamali Hakim, Ahmed Hussain, Hamid Tebyaniyan, Artak Heboyan","doi":"10.1177/09636897241236030","DOIUrl":"10.1177/09636897241236030","url":null,"abstract":"<p><p>The conventional approach for addressing bone defects and stubborn non-unions typically involves the use of autogenous bone grafts. Nevertheless, obtaining these grafts can be challenging, and the procedure can lead to significant morbidity. Three primary treatment strategies for managing bone defects and non-unions prove resistant to conventional treatments: synthetic bone graft substitutes (BGS), a combination of BGS with bioactive molecules, and the use of BGS in conjunction with stem cells. In the realm of synthetic BGS, a multitude of biomaterials have emerged for creating scaffolds in bone tissue engineering (TE). These materials encompass biometals like titanium, iron, magnesium, and zinc, as well as bioceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP). Bone TE scaffolds serve as temporary implants, fostering tissue ingrowth and the regeneration of new bone. They are meticulously designed to enhance bone healing by optimizing geometric, mechanical, and biological properties. These scaffolds undergo continual remodeling facilitated by bone cells like osteoblasts and osteoclasts. Through various signaling pathways, stem cells and bone cells work together to regulate bone regeneration when a portion of bone is damaged or deformed. By targeting signaling pathways, bone TE can improve bone defects through effective therapies. This review provided insights into the interplay between cells and the current state of bioceramics in the context of bone regeneration.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241236030"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10946075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Evolving Function of Vasculature and Pro-angiogenic Therapy in Fat Grafting.","authors":"Zhang Xining, Luo Sai","doi":"10.1177/09636897241264976","DOIUrl":"10.1177/09636897241264976","url":null,"abstract":"<p><p>Autologous fat grating is a widely-accepted method to correct soft tissue deficiency. Although fat transplantation shows excellent biocompatibility and simple applicability, the relatively low retention rate caused by fat necrosis is still a challenge. The vasculature is integral after fat grafting, serving multiple crucial functions. Rapid and effective angiogenesis within grafts is essential for supplying oxygen necessary for adipocytes' survival. It facilitates the influx of inflammatory cells to remove necrotic adipocytes and aids in the delivery of regenerative cells for adipose tissue regeneration in fat grafts. The vasculature also provides a niche for interaction between adipose progenitor cells and vascular progenitor cells, enhancing angiogenesis and adipogenesis in grafts. Various methods, such as enriching grafts with diverse pro-angiogenic cells or utilizing cell-free approaches, have been employed to enhance angiogenesis. Beige and dedifferentiated adipocytes in grafts could increase vessel density. This review aims to outline the function of vasculature in fat grafting and discuss different cell or cell-free approaches that can enhance angiogenesis following fat grafting.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241264976"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11282510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}