Cell Transplantation最新文献

{"title":"Mechanical Unloading Promotes Osteoclastic Differentiation and Bone Resorption by Modulating the MSC Secretome to Favor Inflammation.","authors":"Wanyuji Wang, Xueling Zheng, Hehe Wang, Bin Zuo, Sisi Chen, Jiao Li","doi":"10.1177/09636897241236584","DOIUrl":"10.1177/09636897241236584","url":null,"abstract":"<p><p>Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1^fl/fl;LepRCre), we proved that lack of mechanical stimuli on LepR⁺ mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome of MSCs was regulated by mechanical stimuli. Inadequate mechanical load leads to increased production of inflammatory cytokines, such as interleukin (IL)-1α, IL-6, macrophage colony-stimulating factor 1 (M-CSF-1), and so on, which promotes monocyte proliferation and osteoclastic differentiation. Interestingly, transplantation of 10% cyclic mechanical stretch (CMS)-treated MSCs into HU animals significantly alleviated the BM microenvironment and rebalanced bone remodeling. In summary, our research revealed a new mechanism underlying mechanical unloading-induced bone loss and suggested a novel stem cell-based therapy to potentially prevent disuse-induced osteoporosis.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241236584"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10953070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157666","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":"Preclinical Animal Study and Pilot Clinical Trial of Using Enriched Peripheral Blood-Derived Mononuclear Cells for Intervertebral Disc Degeneration.","authors":"Yu-Hsuan Chung, Ming-Hsien Hu, Shang-Chyi Kao, Ying-Hsien Kao, Fu-Hui Wang, Chia-Ying Hsieh, Ching-I Shen, Chang-Han Chuang, Dave Wei-Chih Chen, Chi-Chung Kuo, Hong-Lin Su, Chih-Lung Lin","doi":"10.1177/09636897231219733","DOIUrl":"10.1177/09636897231219733","url":null,"abstract":"<p><p>Low back pain (LBP) is a leading cause of long-term disability globally. Intervertebral disk degeneration (IVDD) is mainly responsible for discogenic pain in LBP-affected young patients. There is no effective therapy to reverse disease severity and IVDD progression. This study investigates the effect of human peripheral blood-derived mononuclear cells (PBMCs) on pain relief and life quality improvement in IVDD patients. The enriched monocytes of the PBMCs could differentiate into CD14 and CD206 double-positive M2 macrophages <i>in vitro</i>. Preclinical evidence in rats showed that the transplanted PBMCs exhibited anti-inflammatory and moderate tissue-repair effects on controlling IVDD progress in the rat model. The PBMCs significantly steered the aggrecan and type II collagen expressions and attenuated the pro-inflammatory cytokines in the affected disk. Based on the animal results, 36 patients with chronic low back pain (CLBP) were included in clinical trials. The control group was conservative care only, and the experimental group was platelet-rich plasma (PRP) and PBMCs intradiscal injections. We first confirmed the single lumbar disk causing the discogenic pain by provocative discography or magnetic resonance imaging (MRI). Discogenic LBP participants received one intradiscal injection of autologous PBMCs and followed for 6 months. Our clinical trial showed that patients' LBP and disability were significantly ameliorated after the PBMCs transplantation rather than PRP. These preclinical and pilot clinical studies indicate that intradiscal injection of the enriched PBMCs might be a feasible and potential cell therapy to control pain and disability in IVDD patients.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231219733"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086047","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":"CCL3 Promotes Cutaneous Wound Healing Through Recruiting Macrophages in Mice.","authors":"Wanwan Shi, Xunsheng Li, Zhen Wang, Chenguang Li, Datao Wang, Chunyi Li","doi":"10.1177/09636897241264912","DOIUrl":"10.1177/09636897241264912","url":null,"abstract":"<p><p>Wound healing is a complex process, which involves three stages: inflammation, proliferation, and remodeling. Inflammation is the first step; thus, immune factors play an important regulatory role in wound healing. In this study, we focused on a chemokine, C-C motif chemokine ligand 3 (CCL3), which is often upregulated for expression during wound healing. We compared cutaneous wound healing at the histological, morphological, and molecular levels in the presence and absence of CCL3. The results showed that the wound healing rate in the wild-type and CCL3^{-/- + CCL3} mice was faster than that of CCL3^-/- mice (<i>P</i> < 0.01), and application of CCL3 to wounds increased the healing rate. In the process of wound healing, the degree of reepithelialization and the rate of collagen deposition in the wound of CCL3^-/- mice were significantly lower than those of wild-type mice (<i>P</i> < 0.01). The number of macrophages and the expression levels of tumor necrosis factor(TNF)-α and transforming growth factor (TGF)-β1 in the wounds of wild-type mice were much higher than those of the CCL3^-/- mice. Removal of macrophages and CCL3^-/- mice share similar phenotypes. Therefore, we infer that the wound healing requires the participation of macrophages, and CCL3 may play an important regulatory role through recruiting macrophages to the wound sites.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241264912"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792062","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":"Raising the Bar: Progress in 3D-Printed Hybrid Bone Scaffolds for Clinical Applications: A Review.","authors":"Ahsan Riaz Khan, Navdeep Singh Grewal, Zhang Jun, Ferdous M O Tawfiq, Fairouz Tchier, Rana Muhammad Zulqarnain, Hai-Jun Zhang","doi":"10.1177/09636897241273562","DOIUrl":"10.1177/09636897241273562","url":null,"abstract":"<p><p>Damage to bones resulting from trauma and tumors poses a significant challenge to human health. Consequently, current research in bone damage healing centers on developing three-dimensional (3D) scaffolding materials that facilitate and enhance the regeneration of fractured bone tissues. In this context, the careful selection of materials and preparation processes is essential for creating demanding scaffolds for bone tissue engineering. This is done to optimize the regeneration of fractured bones. This study comprehensively analyses the latest scientific advancements and difficulties in developing scaffolds for bone tissue creation. Initially, we clarified the composition and process by which bone tissue repairs itself. The review summarizes the primary uses of materials, both inorganic and organic, in scaffolds for bone tissue engineering. In addition, we present a comprehensive study of the most recent advancements in the mainstream techniques used to prepare scaffolds for bone tissue engineering. We also examine the distinct advantages of each method in great detail. This article thoroughly examines potential paths and obstacles in bone tissue engineering scaffolds for clinical applications.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241273562"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11549696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615477","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":"Establishment of Induced Pancreatic Stem Cells by Yes-Associated Protein 1.","authors":"Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima, Yuka Onishi, Issei Saitoh, Masami Watanabe","doi":"10.1177/09636897241248942","DOIUrl":"10.1177/09636897241248942","url":null,"abstract":"<p><p>Recently, we and others generated induced tissue-specific stem/progenitor (iTS/iTP) cells. The advantages of iTS/iTP cells compared with induced pluripotent stem (iPS) cells are (1) easier generation, (2) efficient differentiation, and (3) no teratomas formation. In this study, we generated mouse induced pancreatic stem cells (iTS-P cells) by the plasmid vector expressing <i>Yes-associated protein 1</i> (<i>YAP</i>). The iTS-P YAP9 cells expressed <i>Foxa2</i> (endoderm marker) and <i>Pdx1</i> (pancreatic marker) while the expressions of <i>Oct3/4</i> and <i>Nanog</i> (marker of embryonic stem [ES] cells) in iTS-P YAP9 cells was significantly lower compared with those in ES cells. The iTS-P YAP9 cells efficiently differentiated into insulin-expressing cells compared with ES cells. The ability to generate autologous iTS cells may be applied to diverse applications of regenerative medicine.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241248942"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849932","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":"Repairing Effect of Mesenchymal Stem Cells on Lead Acetate-Induced Testicular Injury in Mice.","authors":"Shasha Zhao, Zhaozhi Li, Kun Li, Xiaoyu Dai, Zhe Xu, Li Li, Huanhuan Wang, Xiaodun Liu, Dong Li","doi":"10.1177/09636897231219395","DOIUrl":"10.1177/09636897231219395","url":null,"abstract":"<p><p>Lead acetate can cause testicular damage in males. In this study, we assessed the repairing effects of human umbilical cord mesenchymal stem cells (MSCs) on testicular injury caused by lead acetate in mice. MSCs were injected into mice with testicular injury by intraperitoneal injection, and the organ coefficient of reproductive organs, sperm motility, hormone level and antioxidant index of mice were tested. Compared with the normal group, the coefficient of reproductive organs and sperm motility were reduced in the model group, and histopathology showed obvious testicular injury, proving successful modeling. Compared with the model group, the reproductive organ coefficient and sperm motility were improved in the experimental group, and histopathology showed that the testicular injury could be significantly improved. Sex hormone secretion tends to be normal, and the antioxidant index increased. Sequencing results showed that there were 485 upregulated genes and 172 downregulated genes between the model group and the control group, and 210 upregulated genes and 482 downregulated genes between the experimental group and the model group. Differentially expressed genes are mainly concentrated in AMP-activated protein kinase (AMPK) signaling pathway, apoptosis signaling pathway, and arginine biosynthesis signaling pathway. Overall, MSCs can significantly improve the degree of damages to mice testis caused by lead acetate and have a certain repairing effect.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231219395"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10768580/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086048","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":"Retraction notice: Tumor Suppressor Gene XEDAR Promotes Differentiation and Suppresses Proliferation and Migration of Gastric Cancer Cells Through Upregulating the RELA/LXRα Axis and Deactivating the Wnt/β-Catenin Pathway.","authors":"","doi":"10.1177/09636897241310845","DOIUrl":"10.1177/09636897241310845","url":null,"abstract":"","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241310845"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863334","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":"Human Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Multiple Sclerosis Patients: Phase I/II Dose-Finding Clinical Study.","authors":"Fatima Jamali, Mayis Aldughmi, Serin Atiani, Ali Al-Radaideh, Said Dahbour, Dana Alhattab, Hind Khwaireh, Sally Arafat, Joud Al Jaghbeer, Reem Rahmeh, Kawthar Abu Moshref, Hisham Bawaneh, Mona R Hassuneh, Bayan Hourani, Osameh Ababneh, Alia Alghwiri, Abdalla Awidi","doi":"10.1177/09636897241233045","DOIUrl":"10.1177/09636897241233045","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic neuro-inflammatory disease resulting in disabilities that negatively impact patients' life quality. While current treatment options do not reverse the course of the disease, treatment using mesenchymal stromal/stem cells (MSC) is promising. There has yet to be a consensus on the type and dose of MSC to be used in MS. This work aims to study the safety and efficacy of two treatment protocols of MSCs derived from the umbilical cord (UC-MSCs) and their secretome. The study included two groups of MS patients; Group A received two intrathecal doses of UC-MSCs, and Group B received a single dose. Both groups received UC-MSCs conditioned media 3 months post-treatment. Adverse events in the form of a clinical checklist and extensive laboratory tests were performed. Whole transcriptome analysis was performed on patients' cells at baseline and post-treatment. Results showed that all patients tolerated the cellular therapy without serious adverse events. The general disability scale improved significantly in both groups at 6 months post-treatment. Examining specific aspects of the disease revealed more parameters that improved in Group A compared to Group B patients, including a significant increase in the (CD3⁺CD4⁺) expressing lymphocytes at 12 months post-treatment. In addition, better outcomes were noted regarding lesion load, cortical thickness, manual dexterity, and information processing speed. Both protocols impacted the transcriptome of treated participants with genes, transcription factors, and microRNAs (miRNAs) differentially expressed compared to baseline. Inflammation-related and antigen-presenting (HLA-B) genes were downregulated in both groups. In contrast, TNF-alpha, TAP-1, and miR142 were downregulated only in Group A. The data presented indicate that both protocols are safe. Furthermore, it suggests that administering two doses of stem cells can be more beneficial to MS patients. Larger multisite studies should be initiated to further examine similar or higher doses of MSCs.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241233045"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10921855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048823","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":"Transplantation of Exosomes Derived From Human Wharton's Jelly Mesenchymal Stromal Cells Enhances Functional Improvement in Stroke Rats.","authors":"Yu-Sung Chiu, Kuo-Jen Wu, Seong-Jin Yu, Kun-Lieh Wu, Chang-Yi Hsieh, Yu-Sheng Chou, Kuan-Yu Chen, Yu-Syuan Wang, Eun-Kyung Bae, Tsai-Wei Hung, Shih-Hsun Lin, Chih-Hsueh Lin, Shu-Ching Hsu, Yun Wang, Yun-Hsiang Chen","doi":"10.1177/09636897241296366","DOIUrl":"10.1177/09636897241296366","url":null,"abstract":"<p><p>Cerebral ischemic stroke is a major cerebrovascular disease and the leading cause of adult disability. We and others previously demonstrated that transplantation of human Wharton's jelly mesenchymal stromal cells (WJ-MSCs) attenuated neuronal damage and promoted functional improvement in stroke animals. This study aimed to investigate the protective effects of human WJ-MSC exosome (Exo) transplant in cellular and rat models of cerebral stroke. Administration of Exo significantly antagonized glutamate-mediated neuronal loss and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X nick end labeling (TUNEL) in rat primary cortical neuronal cultures. Adult male rats underwent a 60-min middle cerebral artery occlusion (MCAo); Exo or vehicle was injected through the tail vein 5-10 min after the MCAo. Two days later, the rats underwent a series of behavioral tests. Stroke rats receiving Exo developed a significant improvement in locomotor function and forelimb strength while reductions in body asymmetry and Bederson's neurological score. After the behavioral test, brain tissues were harvested for histological and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analyses. Animals receiving Exo had less infarction volume, measured by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Transplantation of Exo increased the expression of protective neurotrophic factors (BMP7, GDNF) and anti-apoptotic factors (Bcl2, Bcl-xL) in the ischemic brain. These findings suggest that early post-treatment with WJ-MSC Exo, given non-invasively through the vein, improved functional recovery and reduced brain damage in the stroke brain.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241296366"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766510","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":"A Difficult Case of Calcineurin Inhibitor Neurotoxicity Post-Haploidentical HCT With a Successful Novel Solution: Cytotoxic T-Lymphocyte-Associated Protein 4-Immunoglobulin Blockade for GVHD Prophylaxis.","authors":"Kaitlyn Dykes, Dimitrios Tzachanis, Divya Koura","doi":"10.1177/09636897241265249","DOIUrl":"10.1177/09636897241265249","url":null,"abstract":"<p><p>Post-allogeneic hematopoietic cell transplant (HCT) immunosuppression regimens are given as graft-versus-host disease (GVHD) prophylaxis. Most GVHD prophylaxis regimens are based on calcineurin inhibitors (CNIs). Unfortunately, CNIs are associated with significant associated morbidity, frequently cannot be tolerated, and often need to be discontinued. There is no consensus as to which alternative immunosuppression should be used in cases where CNIs have to be permanently discontinued. Cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocking agents are well tolerated and have been used extensively in patients with autoimmune disease and as post-transplant immunosuppression. There are two CTLA4-Ig agents: belatacept and abatacept. Belatacept is routinely used in adult kidney transplantation to prevent rejection and abatacept has been approved by the Food and Drug Administration (FDA) for GVHD prophylaxis in patients undergoing a matched or one allele-mismatched unrelated allogenic HCT. Herein, we describe a case in which abatacept was given off-label to replace tacrolimus GVHD prophylaxis in a patient with neurotoxicity undergoing haploidentical HCT. This case suggests that CTLA4-Ig blockade may be a good alternative to a CNI in cases where the CNI needs to be discontinued and warrants further investigation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241265249"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792061","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}