{"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}
Min Wang, Linfeng Zhang, Haojie Hao, Muyang Yan, Ziying Zhu
{"title":"Applications of Engineered Skin Tissue for Cosmetic Component and Toxicology Detection.","authors":"Min Wang, Linfeng Zhang, Haojie Hao, Muyang Yan, Ziying Zhu","doi":"10.1177/09636897241235464","DOIUrl":"10.1177/09636897241235464","url":null,"abstract":"<p><p>The scale of the cosmetic market is increasing every day. There are many safety risks to cosmetics, but they benefit people at the same time. The skin can become red, swollen, itchy, chronically toxic, and senescent due to the misuse of cosmetics, triggering skin injuries, with contact dermatitis being the most common. Therefore, there is an urgent need for a system that can scientifically and rationally detect the composition and perform a toxicological assessment of cosmetic products. Traditional detection methods rely on instrumentation and method selection, which are less sensitive and more complex to perform. Engineered skin tissue has emerged with the advent of tissue engineering technology as an emerging bioengineering technology. The ideal engineered skin tissue is the basis for building good <i>in vitro</i> structures and physiological functions in this field. This review introduces the existing cosmetic testing and toxicological evaluation methods, the current development status, and the types and characteristics of engineered skin tissue. The application of engineered skin tissue in the field of cosmetic composition detection and toxicological evaluation, as well as the different types of tissue engineering scaffold materials and three-dimensional (3D) organoid preparation approaches, is highlighted in this review to provide methods and ideas for constructing the next engineered skin tissue for cosmetic raw material component analysis and toxicological evaluation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241235464"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140140037","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}
Linbin Li, Yunxi Yang, Zaiwen Guo, Xi Gao, Lu Liu, Jiamin Huang, Bingwei Sun
{"title":"Investigation of Allogeneic Neutrophil Transfusion in Improving Survival Rates of Severe Infection Mice.","authors":"Linbin Li, Yunxi Yang, Zaiwen Guo, Xi Gao, Lu Liu, Jiamin Huang, Bingwei Sun","doi":"10.1177/09636897241228031","DOIUrl":"10.1177/09636897241228031","url":null,"abstract":"<p><p>The management of granulocytopenia-associated infections is challenging, and a high mortality rate is associated with traditional supportive therapies. Neutrophils-the primary defenders of the human immune system-have potent bactericidal capabilities. Here, we investigated the dynamic in vivo distribution of neutrophil transfusion and their impact on the treatment outcome of severe granulocytopenic infections. We transfused <sup>89</sup>Zr-labeled neutrophils in the C57BL/6 mice and observed the dynamic neutrophil distribution in mice for 24 h using the micro-positron emission tomography (Micro-PET) technique. The labeled neutrophils were predominantly retained in the lungs and spleen up to 4 h after injection and then redistributed to other organs, such as the spleen, liver, and bone marrow. Neutrophil transfusion did not elicit marked inflammatory responses or organ damage in healthy host mice. Notably, allogeneic neutrophils showed rapid chemotaxis to the infected area of the host within 1 h. Tail vein infusion of approximately 10<sup>7</sup> neutrophils substantially bolstered host immunity, ameliorated the inflammatory state, and increased survival rates in neutrophil-depleted and infected mice. Overall, massive allogeneic neutrophil transfusion had a therapeutic effect in severe infections and can have extensive applications in the future.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241228031"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729102","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}
Carl Randall Harrell, Ana Volarevic, Valentin Djonov, Aleksandar Arsenijevic, Vladislav Volarevic
{"title":"The Role of MicroRNAs in Mesenchymal Stem Cell-Based Modulation of Pulmonary Fibrosis.","authors":"Carl Randall Harrell, Ana Volarevic, Valentin Djonov, Aleksandar Arsenijevic, Vladislav Volarevic","doi":"10.1177/09636897241281026","DOIUrl":"10.1177/09636897241281026","url":null,"abstract":"<p><p>Pulmonary fibrosis is a complex and multifactorial condition that involves a cascade of events, including lung injury, damage of alveolar epithelial cells (AECs), generation of immune cell-driven inflammation, and activation of fibroblasts and their differentiation into myofibroblasts, resulting in the excessive production and deposition of collagen and progressive scarring and fibrosis of the lung tissue. As lung fibrosis advances, the scarring and stiffening of lung tissue can significantly hinder the exchange of oxygen and carbon dioxide, potentially leading to respiratory failure that can be life-threatening. Anti-inflammatory and immunosuppressive drugs are used to slow down the progression of the disease, manage symptoms, and enhance the patient's quality of life. However, prolonged immunosuppression could increase the susceptibility to severe bacterial, viral, or fungal pneumonia in lung-transplant recipients. Therefore, there is an urgent need for new therapeutic agents that can effectively reduce lung inflammation and fibrosis without compromising the protective immune response in patients with severe lung fibrosis. Results obtained in recently published studies demonstrated that mesenchymal stem/stromal cell-derived microRNAs (MSC-miRNAs) could attenuate detrimental immune response in injured lungs and prevent progression of lung fibrosis. Through the post-transcriptional regulation of target mRNA, MSC-miRNAs modulate protein synthesis and affect viability, proliferation, and cytokine production in AECs, fibroblasts, and lung-infiltrated immune cells. In order to delineate molecular mechanisms responsible for beneficial effects of MSC-miRNAs in the treatment of lung fibrosis, in this review article, we summarized current knowledge related to anti-fibrotic and anti-inflammatory pathways elicited in immune cells, AECs, and myofibroblasts by MSC-miRNAs.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241281026"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342459","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":"EXPRESSION OF CONCERN: Pericardial Grafting of Cardiac Progenitor Cells in Self-Assembling Peptide Scaffold Improves Cardiac Function After Myocardial Infarction.","authors":"","doi":"10.1177/09636897241255859","DOIUrl":"10.1177/09636897241255859","url":null,"abstract":"","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241255859"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908509","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 Novel Approach to Orthotopic Hepatocyte Transplantation Engineered With Liver Hydrogel for Fibrotic Livers, Enhancing Cell-Cell Interaction and Angiogenesis.","authors":"Daisuke Udagawa, Shogo Nagata, Hiroshi Yagi, Kotaro Nishi, Toshinori Morisaku, Shungo Adachi, Yutaka Nakano, Masayuki Tanaka, Shutaro Hori, Yasushi Hasegawa, Yuta Abe, Minoru Kitago, Yuko Kitagawa","doi":"10.1177/09636897241253700","DOIUrl":"10.1177/09636897241253700","url":null,"abstract":"<p><p>Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet to overcome poor cell engraftment and function. Therefore, we developed an orthotopic HCT method using a liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into the hydrogel solution in vitro, and the gel solution was immediately gelated in 37°C incubators to investigate the affinity between mature human hepatocyte and the L-ECM gel. During the 3-day cultivation in hepatocyte medium, PXB cells formed cell aggregates via cell-cell interactions. Quantitative analysis revealed human albumin production in culture supernatants. For the <i>in vivo</i> assay, PXB cells were encapsulated in the L-ECM gel and transplanted between the liver lobes of normal rats. Pathologically, the L-ECM gel was localized at the transplant site and retained PXB cells. Cell survival and hepatic function marker expression were verified in another rat model wherein thioacetamide was administered to induce liver fibrosis. Moreover, cell-cell interactions and angiogenesis were enhanced in the L-ECM gel compared with that in the collagen gel. Our results indicate that L-ECM gels can help engraft transplanted hepatocytes and express hepatic function as a scaffold for cell transplantation.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241253700"},"PeriodicalIF":3.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069973","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}
Paeng Sunwoong, Yeri Alice Rim, Yeowon Sohn, Yoojun Nam, Ji Hyeon Ju
{"title":"Exploration of Efficient HLA Haplotypes by Comparing the Proportion of Applicable Populations.","authors":"Paeng Sunwoong, Yeri Alice Rim, Yeowon Sohn, Yoojun Nam, Ji Hyeon Ju","doi":"10.1177/09636897241283539","DOIUrl":"https://doi.org/10.1177/09636897241283539","url":null,"abstract":"<p><p>With the aging population, the incidence of degenerative diseases such as dementia and arthritis is on the rise. To combat these diseases, cell therapies using induced pluripotent stem cells (iPSCs) are being developed worldwide. However, challenges such as high development costs and immune compatibility persist. Thus, methods such as generating patient-specific iPSCs or genetically edited iPSCs with deleted immune-related genes are being researched. Applying these approaches is limited due to high cost and safety concerns of gene editing. Therefore, we focused on an alternative method using human leukocyte antigen (HLA)-homozygous cell lines, which could overcome immune rejection issues economically. We investigated diseases that could potentially be treated with cell therapy and identified which HLA-homozygous cell lines could be most effectively used for the efficient production of therapeutic cell lines. The results of the study showed that cell therapy could be applied to a wide range of diseases, and expanding the population that can benefit from HLA-homozygous iPSC lines could help popularize these treatment methods. We highlight the necessity of a global HLA-homozygous iPSC bank.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241283539"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11504281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495884","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":"Novel Strategies for Spatiotemporal and Controlled BMP-2 Delivery in Bone Tissue Engineering.","authors":"Jingqi Qi, Hongwei Wu, Gengyan Liu","doi":"10.1177/09636897241276733","DOIUrl":"10.1177/09636897241276733","url":null,"abstract":"<p><p>Bone morphogenetic protein-2 (BMP-2) has been commercially approved by the Food and Drug Administration for use in bone defects and diseases. BMP-2 promotes osteogenic differentiation of mesenchymal stem cells. In bone tissue engineering, BMP-2 incorporated into scaffolds can be used for stimulating bone regeneration in organoid construction, drug testing platforms, and bone transplants. However, the high dosage and uncontrollable release rate of BMP-2 challenge its clinical application, mainly due to the short circulation half-life of BMP-2, microbial contamination in bone extracellular matrix hydrogel, and the delivery method. Moreover, in clinical translation, the requirement of high doses of BMP-2 for efficacy poses challenges in cost and safety. Based on these, novel strategies should ensure that BMP-2 is delivered precisely to the desired location within the body, regulating the timing of BMP-2 release to coincide with the bone healing process, as well as release BMP-2 in a controlled manner to optimize its therapeutic effect and minimize side effects. This review highlights improvements in bone tissue engineering applying spatiotemporal and controlled BMP-2 delivery, including molecular engineering, biomaterial modification, and synergistic therapy, aiming to provide references for future research and clinical trials.</p>","PeriodicalId":9721,"journal":{"name":"Cell Transplantation","volume":"33 ","pages":"9636897241276733"},"PeriodicalIF":3.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280887","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}