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
{"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<sup>-/- + CCL3</sup> mice was faster than that of CCL3<sup>-/-</sup> 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<sup>-/-</sup> 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<sup>-/-</sup> mice. Removal of macrophages and CCL3<sup>-/-</sup> 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}
Ahsan Riaz Khan, Navdeep Singh Grewal, Zhang Jun, Ferdous M O Tawfiq, Fairouz Tchier, Rana Muhammad Zulqarnain, Hai-Jun Zhang
{"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}
Shasha Zhao, Zhaozhi Li, Kun Li, Xiaoyu Dai, Zhe Xu, Li Li, Huanhuan Wang, Xiaodun Liu, Dong Li
{"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}
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
{"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<sup>+</sup>CD4<sup>+</sup>) 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":"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":"https://doi.org/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":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Proliferation and Differentiation Potential of Bone Marrow-Derived Mesenchymal Stem Cells From Children With Polydactyly and Adults With Basal Joint Arthritis.","authors":"Shih-Han Yeh, Jin-Huei Yu, Po-Hsin Chou, Szu-Hsien Wu, Yu-Ting Liao, Yi-Chao Huang, Tung-Ming Chen, Jung-Pan Wang","doi":"10.1177/09636897231221878","DOIUrl":"10.1177/09636897231221878","url":null,"abstract":"<p><p>This study compared the proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells (BMSCs) derived from infants with polydactyly and adults with basal joint arthritis. The proliferation rate of adult and infant BMSCs was determined by the cell number changes and doubling times. The γH2AX immunofluorescence staining, age-related gene expression, senescence-associated β-galactosidase (SA-β-gal) staining were analyzed to determine the senescence state of adult and infant BMSCs. The expression levels of superoxide dismutases (SODs) and genes associated with various types of differentiation were measured using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR). Differentiation levels were evaluated through histochemical and immunohistochemical staining. The results showed that infant BMSCs had a significantly higher increase in cell numbers and faster doubling times compared with adult BMSCs. Infant BMSCs at late stages exhibited reduced γH2AX expression and SA-β-gal staining, indicating lower levels of senescence. The expression levels of senescence-related genes (<i>p16</i>, <i>p21</i>, and <i>p53</i>) in infant BMSCs were also lower than in adult BMSCs. In addition, infant BMSCs demonstrated higher antioxidative ability with elevated expression of <i>SOD1</i>, <i>SOD2</i>, and <i>SOD3</i> compared with adult BMSCs. In terms of differentiation potential, infant BMSCs outperformed adult BMSCs in chondrogenesis, as indicated by higher expression levels of chondrogenic genes (<i>SOX9</i>, <i>COL2</i>, and <i>COL10</i>) and positive immunohistochemical staining. Moreover, differentiated cells derived from infant BMSCs exhibited significantly higher expression levels of osteogenic, tenogenic, hepatogenic, and neurogenic genes compared with those derived from adult BMSCs. Histochemical and immunofluorescence staining confirmed these findings. However, adult BMSCs showed lower adipogenic differentiation potential compared with infant BMSCs. Overall, infant BMSCs demonstrated superior characteristics, including higher proliferation rates, enhanced antioxidative activity, and greater differentiation potential into various lineages. They also exhibited reduced cellular senescence. These findings, within the context of cellular differentiation, suggest potential implications for the use of allogeneic BMSC transplantation, emphasizing the need for further <i>in vivo</i> investigation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231221878"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073446","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":"Relapsed/Refractory Peripheral T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis With UNC13D and CD27 Germline Mutations.","authors":"Tingting Yang, Rongrong Chen, Mingming Zhang, Ruirui Jing, Jia Geng, Guoqing Wei, Yi Luo, Pingnan Xiao, Ruimin Hong, Jingjing Feng, Shan Fu, Houli Zhao, Jiazhen Cui, Simao Huang, He Huang, Yongxian Hu","doi":"10.1177/09636897231221887","DOIUrl":"10.1177/09636897231221887","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory disease characterized by familial and acquired forms. Here, we present the case of a 26-year-old male patient with relapsed/refractory peripheral T-cell lymphoma and concurrent HLH. Whole-exon sequencing revealed germline mutations associated with HLH, including those in critical genes such as <i>CD27</i> and <i>UNC13D</i> and other germline heterozygous variants (<i>NOTCH2, NOTCH3, IL2RA, TYK2, AGL, CFD</i>, and <i>F13A1</i>). CD107a analyses consistently demonstrated impaired degranulation of cytotoxic T-lymphocytes and natural killer (NK) cells. Examination of the patient's family pedigree revealed that his father and mother harbored <i>UNC13D</i> and <i>CD27</i> mutations, respectively; his brother carried the same <i>CD27</i> heterozygous mutation. However, none of them manifested the disease. Despite the missense mutation of <i>CD27</i> (c.779C>T; p.Pro260Leu) lacking previous documentation in databases, comprehensive analysis suggested non-pathogenic mutations in the <i>CD27</i> variant, indicating minimal impact on T- and NK-cell functions. These results ultimately supported the option of hematopoietic stem cell transplantation (HSCT) as a successful curative therapeutic approach. As of this report, the patient has remained free of lymphoma and quiescent HLH 15.2 months post-HSCT. This study underscores the efficacy of genetic tests in identifying significant mutations and confirming their etiologies, providing an early basis for treatment decisions and the selection of suitable transplant donors.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231221887"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10771736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139105888","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}
Yun Bai, Yichao Du, Yin Yang, Thomas Wälchli, Paul E Constanthin, Fan Li
{"title":"Ultrasound-Targeted Microbubble Destruction Increases BBB Permeability and Promotes Stem Cell-Induced Regeneration of Stroke by Downregulating MMP8.","authors":"Yun Bai, Yichao Du, Yin Yang, Thomas Wälchli, Paul E Constanthin, Fan Li","doi":"10.1177/09636897231223293","DOIUrl":"10.1177/09636897231223293","url":null,"abstract":"<p><p>The objective of this study was to evaluate the feasibility, safety, and effectiveness of intravenous stem cell delivery utilizing ultrasound-targeted microbubble destruction (UTMD) in a rat model of middle cerebral artery occlusion (MCAO), while investigating the underlying mechanisms. Acute cerebral infarction (ACI) was induced surgically in adult rats to create the MCAO rat model. Intravenous injection of SonoVue microbubbles and bone marrow-derived mesenchymal stem cells (BMSC) was performed concurrently, with or without ultrasound targeting the stroke. The animals were divided into four groups: sham-operated group, ACI-MCAO rats treated with phosphate-buffered saline (ACI+PBS), rats receiving intravenous delivery of BMSC expressing green fluorescent protein (GFP-BMSC; ACI+BMSC), and rats receiving intravenous GFP-BMSC with simultaneous UTMD exposure (ACI+BMSC+UTMD). The efficacy of the treatments was assessed by evaluating the animals' neurological function using the Longa score and examining histopathological changes such as cerebral infarct volume, cerebral edema, and cell apoptosis. A rat cytokine array was utilized to identify the potential cytokines that may be responsible for the therapeutic effect of UTMD-mediated BMSC treatment. Optimal UTMD parameters resulted in an increase in blood-brain barrier (BBB) permeability after 30 min, which returned to baseline 72 h later without causing any residual injury. UTMD application significantly increased the homing of intravenously delivered BMSC, resulting in a 2.2-fold increase in GFP-BMSC cell count on day 3 and a 2.6-fold increase on day 7 compared with intravenous delivery alone. This effect persisted for up to 6 weeks after injection. Intravenous BMSC delivery significantly reduced the volume of cerebral infarct and decreased cerebral edema, leading to a lower Longa score. Furthermore, this effect was further enhanced by UTMD. Acute cerebral infarction induced by MCAO led to elevated matrix metalloproteinase 8 (MMP8) levels in the cerebrospinal fluid, which were significantly reduced following UTMD-mediated BMSC treatment. <b>U</b>ltrasound-targeted microbubble destruction facilitates the migration and homing of BMSC into the brain, possibly by transiently increasing blood-brain barrier (BBB) permeability, thereby improving therapeutic outcomes in an ACI rat model. The observed effect may be partly attributed to modulation of MMP8 levels.<b>Advances in knowledge:</b> UTMD-mediated intravenously delivered BMSC transplantation led to a significant increase in cell homing and reduction of MMP8 levels, resulting in increased therapeutic effect in an acute ischemic cerebral infarction model.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897231223293"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10777784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402035","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}