Jingwen Hu, George S Melchor, Dimitrios Ladakis, Joan Reger, Hee Won Kim, Kelly A Chamberlain, Nataliia V Shults, Helena C Oft, Victoria N Smith, Lauren M Rosko, Erqiu Li, Maryna Baydyuk, Meng-Meng Fu, Pavan Bhargava, Jeffrey K Huang
{"title":"Myeloid cell-associated aromatic amino acid metabolism facilitates CNS myelin regeneration.","authors":"Jingwen Hu, George S Melchor, Dimitrios Ladakis, Joan Reger, Hee Won Kim, Kelly A Chamberlain, Nataliia V Shults, Helena C Oft, Victoria N Smith, Lauren M Rosko, Erqiu Li, Maryna Baydyuk, Meng-Meng Fu, Pavan Bhargava, Jeffrey K Huang","doi":"10.1038/s41536-023-00345-9","DOIUrl":"10.1038/s41536-023-00345-9","url":null,"abstract":"<p><p>Regulation of myeloid cell activity is critical for successful myelin regeneration (remyelination) in demyelinating diseases, such as multiple sclerosis (MS). Here, we show aromatic alpha-keto acids (AKAs) generated from the amino acid oxidase, interleukin-4 induced 1 (IL4I1), promote efficient remyelination in mouse models of MS. During remyelination, myeloid cells upregulated the expression of IL4I1. Conditionally knocking out IL4I1 in myeloid cells impaired remyelination efficiency. Mice lacking IL4I1 expression exhibited a reduction in the AKAs, phenylpyruvate, indole-3-pyruvate, and 4-hydroxyphenylpyruvate, in remyelinating lesions. Decreased AKA levels were also observed in people with MS, particularly in the progressive phase when remyelination is impaired. Oral administration of AKAs modulated myeloid cell-associated inflammation, promoted oligodendrocyte maturation, and enhanced remyelination in mice with focal demyelinated lesions. Transcriptomic analysis revealed AKA treatment induced a shift in metabolic pathways in myeloid cells and upregulated aryl hydrocarbon receptor activity in lesions. Our results suggest myeloid cell-associated aromatic amino acid metabolism via IL4I1 produces AKAs in demyelinated lesions to enable efficient remyelination. Increasing AKA levels or targeting related pathways may serve as a strategy to facilitate the regeneration of myelin in inflammatory demyelinating conditions.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"9 1","pages":"1"},"PeriodicalIF":6.4,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10762216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Type I collagen and fibromodulin enhance the tenogenic phenotype of hASCs and their potential for tendon regeneration","authors":"Tian Tu, Yuan Shi, Boya Zhou, Xiaoyu Wang, Wenjie Zhang, Guangdong Zhou, Xiumei Mo, Wenbo Wang, Jinglei Wu, Wei Liu","doi":"10.1038/s41536-023-00341-z","DOIUrl":"https://doi.org/10.1038/s41536-023-00341-z","url":null,"abstract":"<p>Our previous work demonstrated the tendon-derived extracellular matrix (ECM) extracts as vital niches to specifically direct mesenchymal stem cells towards tenogenic differentiation. This study aims to further define the effective ECM molecules capable of teno-lineage induction on human adipose-derived stem cells (hASCs) and test their function for tendon engineering. By detecting the teno-markers expression levels in hASCs exposed to various substrate coatings, collagen I (COL1) and fibromodulin (FMOD) were identified to be the key molecules as a combination and further employed to the modification of poly(L-lactide-<i>co</i>-ε-caprolactone) electrospun nanoyarns, which showed advantages in inducting seeded hASCs for teno-lineage specific differentiation. Under dynamic mechanical loading, modified scaffold seeded with hASCs formed neo-tendon in vitro at the histological level and formed better tendon tissue in vivo with mature histology and enhanced mechanical properties. Primary mechanistic investigation with RNA sequencing demonstrated that the inductive mechanism of these two molecules for hASCs tenogenic differentiation was directly correlated with positive regulation of peptidase activity, regulation of cell-substrate adhesion and regulation of cytoskeletal organization. These biological processes were potentially affected by LOC101929398/has-miR-197-3p/TENM4 ceRNA regulation axis. In summary, COL1 and FMOD in combination are the major bioactive molecules in tendon ECM for likely directing tenogenic phenotype of hASCs and certainly valuable for hASCs-based tendon engineering.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"237 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hyerim Kim, Hyeonhee Roh, Sang-Heon Kim, Kangwon Lee, Maesoon Im, Seung Ja Oh
{"title":"Effective protection of photoreceptors using an inflammation-responsive hydrogel to attenuate outer retinal degeneration","authors":"Hyerim Kim, Hyeonhee Roh, Sang-Heon Kim, Kangwon Lee, Maesoon Im, Seung Ja Oh","doi":"10.1038/s41536-023-00342-y","DOIUrl":"https://doi.org/10.1038/s41536-023-00342-y","url":null,"abstract":"<p>Retinitis pigmentosa (RP) is an outer retinal degenerative disease that can lead to photoreceptor cell death and profound vision loss. Although effective regulation of intraretinal inflammation can slow down the progression of the disease, an efficient anti-inflammatory treatment strategy is still lacking. This study reports the fabrication of a hyaluronic acid-based inflammation-responsive hydrogel (IRH) and its epigenetic regulation effects on retinal degeneration. The injectable IRH was designed to respond to cathepsin overexpression in an inflammatory environment. The epigenetic drug, the enhancer of zeste homolog 2 (EZH2) inhibitors, was loaded into the hydrogel to attenuate inflammatory factors. On-demand anti-inflammatory effects of microglia cells via the drug-loaded IRH were verified in vitro and in vivo retinal degeneration 10 (<i>rd10</i>) mice model. Therefore, our IRH not only reduced intraretinal inflammation but also protected photoreceptors morphologically and functionally. Our results suggest the IRH reported here can be used to considerably delay vision loss caused by RP.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"23 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138681776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Harnessing bioengineered myeloid progenitors for precision immunotherapies","authors":"Willem Buys, Elias T. Zambidis","doi":"10.1038/s41536-023-00343-x","DOIUrl":"https://doi.org/10.1038/s41536-023-00343-x","url":null,"abstract":"<p>Granulocytes and macrophages are the frontline defenders of the innate immune system. These myeloid cells play a crucial role in not only eliminating pathogens and tumor cells, but also regulating adaptive immune responses. In neonatal sepsis and post-chemotherapy agranulocytosis, the absence of these cells leaves the host highly vulnerable to infections. Beyond replacement to prevent or control neutropenic sepsis, engineered myeloid cells may offer distinct opportunities for cell therapies. For example, the mobility and specific homing capacities of neutrophils to sites of inflammation could be exploited to deliver biocidal agents, or anti-inflammatory healing signals during sepsis, autoimmunity, and organ transplantation. Additionally, myeloid cells can be engineered to express chimeric antigen receptors (CAR), carry chemotherapeutics, or enhance lymphoid tumor killing. However, traditional methods of cell isolation are incapable of providing sufficient cell numbers of these short-lived cells; their propensity for premature activation further complicates their cell engineering. Here, we review current and future biotherapeutic innovations that employ engineered multipotent myeloid progenitors derived from either self-renewing human induced pluripotent stem cells (hiPSC) or primary CD34<sup>+</sup> hematopoietic stem-progenitors. We provide a roadmap for solving the challenges of sourcing, cost, and production of engineered myeloid cell therapies.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"4 1","pages":""},"PeriodicalIF":7.2,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138630186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingxing Lei, Jingwei Jiang, Mengyue Wang, Wang Wu, Jinwei Zhang, Wanqian Liu, Wei Zhou, Yung-Chih Lai, Ting-Xin Jiang, Randall B Widelitz, Hans I-Chen Harn, Li Yang, Cheng-Ming Chuong
{"title":"Epidermal-dermal coupled spheroids are important for tissue pattern regeneration in reconstituted skin explant cultures.","authors":"Mingxing Lei, Jingwei Jiang, Mengyue Wang, Wang Wu, Jinwei Zhang, Wanqian Liu, Wei Zhou, Yung-Chih Lai, Ting-Xin Jiang, Randall B Widelitz, Hans I-Chen Harn, Li Yang, Cheng-Ming Chuong","doi":"10.1038/s41536-023-00340-0","DOIUrl":"10.1038/s41536-023-00340-0","url":null,"abstract":"<p><p>Tissue patterning is critical for the development and regeneration of organs. To advance the use of engineered reconstituted skin organs, we study cardinal features important for tissue patterning and hair regeneration. We find they spontaneously form spheroid configurations, with polarized epidermal cells coupled with dermal cells through a newly formed basement membrane. Functionally, the spheroid becomes competent morphogenetic units (CMU) that promote regeneration of tissue patterns. The emergence of new cell types and molecular interactions during CMU formation was analyzed using scRNA-sequencing. Surprisingly, in newborn skin explants, IFNr signaling can induce apical-basal polarity in epidermal cell aggregates. Dermal-Tgfb induces basement membrane formation. Meanwhile, VEGF signaling mediates dermal cell attachment to the epidermal cyst shell, thus forming a CMU. Adult mouse and human fetal scalp cells fail to form a CMU but can be restored by adding IFNr or VEGF to achieve hair regeneration. We find different multi-cellular configurations and molecular pathways are used to achieve morphogenetic competence in developing skin, wound-induced hair neogenesis, and reconstituted explant cultures. Thus, multiple paths can be used to achieve tissue patterning. These insights encourage more studies of \"in vitro morphogenesis\" which may provide novel strategies to enhance regeneration.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"65"},"PeriodicalIF":7.2,"publicationDate":"2023-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10667216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138300578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingyi Shen, Ying Wang, Fei Zheng, Shuo Cao, Qiu Lan, Kailin Xu, Bin Pan
{"title":"Aryl hydrocarbon receptor regulates IL-22 receptor expression on thymic epithelial cell and accelerates thymus regeneration.","authors":"Jingyi Shen, Ying Wang, Fei Zheng, Shuo Cao, Qiu Lan, Kailin Xu, Bin Pan","doi":"10.1038/s41536-023-00339-7","DOIUrl":"10.1038/s41536-023-00339-7","url":null,"abstract":"<p><p>Improving regeneration of damaged thymus is important for reconstituting T-cell immunity. Interleukin-22 (IL-22) was proved to improve thymus regeneration through recovering thymic epithelial cells (TECs). The IL-22 receptor IL-22RA1 is crucial for mediating IL-22 functions. Mechanism that regulates IL-22RA1 expression is unknown. Through using TECs-conditional knockout mice, we found aryl hydrocarbon receptor (AHR) is important for thymus regeneration, because Foxn1-cre-mediated AHR knockout (AhrKO) significantly blocks recovery of thymus cells. Giving mice the AHR inhibitor CH-223191 or the AHR agonist FICZ blocks or accelerates thymus regeneration, respectively. AhrKO-mediated blockade of thymus regeneration could not be rescued by giving exogenous IL-22. Mechanistically, AhrKO mice shows decreased IL-22RA1 expression. In the murine TECs cell line mTEC1 cells, targeting AHR shows an impact on IL-22RA1 mRNA levels. Using chromatin immunoprecipitation and luciferase reporter assays, we find AHR co-operates with STAT3, binds the promotor region of IL-22RA1 gene and transcriptionally increases IL-22RA1 expression in mTEC1 cells. Foxn1-cre-mediated IL-22RA1 knockout (Il22ra1KO) blocks thymus regeneration after irradiation. Furthermore, targeting AHR or IL-22RA1 has significant impacts on severity of murine chronic graft-versus-host disease (cGVHD), which is an autoimmune-like complication following allogeneic hematopoietic cell transplantation. Giving FICZ decreases cGVHD, whereas Il22ra1KO exacerbates cGVHD. The impacts on cGVHD are associated with thymus regeneration and T-cell immune reconstitution. In conclusion, we report an unrecognized function of TECs-expressed AHR in thymus regeneration and AHR transcriptionally regulates IL-22RA1 expression, which have implications for improving thymus regeneration and controlling cGVHD.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"64"},"PeriodicalIF":7.2,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viktoriia Iakovleva, Anna Wuestefeld, Agnes Bee Leng Ong, Rong Gao, Neslihan Arife Kaya, May Yin Lee, Weiwei Zhai, Wai Leong Tam, Yock Young Dan, Torsten Wuestefeld
{"title":"Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment.","authors":"Viktoriia Iakovleva, Anna Wuestefeld, Agnes Bee Leng Ong, Rong Gao, Neslihan Arife Kaya, May Yin Lee, Weiwei Zhai, Wai Leong Tam, Yock Young Dan, Torsten Wuestefeld","doi":"10.1038/s41536-023-00337-9","DOIUrl":"10.1038/s41536-023-00337-9","url":null,"abstract":"<p><p>The liver has a remarkable regenerative capacity. Nevertheless, under chronic liver-damaging conditions, this capacity becomes exhausted, allowing the accumulation of fibrotic tissue and leading to end-stage liver disease. Enhancing the endogenous regenerative capacity by targeting regeneration breaks is an innovative therapeutic approach. We set up an in vivo functional genetic screen to identify such regeneration breaks. As the top hit, we identified Microfibril associated protein 4 (Mfap4). Knockdown of Mfap4 in hepatocytes enhances cell proliferation, accelerates liver regeneration, and attenuates chronic liver disease by reducing liver fibrosis. Targeting Mfap4 modulates several liver regeneration-related pathways including mTOR. Our research opens the way to siRNA-based therapeutics to enhance hepatocyte-based liver regeneration.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"63"},"PeriodicalIF":7.2,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abigail L Lauterbach, Rachel P Wallace, Aaron T Alpar, Kirsten C Refvik, Joseph W Reda, Ako Ishihara, Taryn N Beckman, Anna J Slezak, Yukari Mizukami, Aslan Mansurov, Suzana Gomes, Jun Ishihara, Jeffrey A Hubbell
{"title":"Author Correction: Topically-applied collagen-binding serum albumin-fused interleukin-4 modulates wound microenvironment in non-healing wounds.","authors":"Abigail L Lauterbach, Rachel P Wallace, Aaron T Alpar, Kirsten C Refvik, Joseph W Reda, Ako Ishihara, Taryn N Beckman, Anna J Slezak, Yukari Mizukami, Aslan Mansurov, Suzana Gomes, Jun Ishihara, Jeffrey A Hubbell","doi":"10.1038/s41536-023-00338-8","DOIUrl":"10.1038/s41536-023-00338-8","url":null,"abstract":"","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"62"},"PeriodicalIF":7.2,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dauren Biyashev, Zofia E Siwicka, Ummiye V Onay, Michael Demczuk, Dan Xu, Madison K Ernst, Spencer T Evans, Cuong V Nguyen, Florencia A Son, Navjit K Paul, Naneki C McCallum, Omar K Farha, Stephen D Miller, Nathan C Gianneschi, Kurt Q Lu
{"title":"Topical application of synthetic melanin promotes tissue repair.","authors":"Dauren Biyashev, Zofia E Siwicka, Ummiye V Onay, Michael Demczuk, Dan Xu, Madison K Ernst, Spencer T Evans, Cuong V Nguyen, Florencia A Son, Navjit K Paul, Naneki C McCallum, Omar K Farha, Stephen D Miller, Nathan C Gianneschi, Kurt Q Lu","doi":"10.1038/s41536-023-00331-1","DOIUrl":"10.1038/s41536-023-00331-1","url":null,"abstract":"<p><p>In acute skin injury, healing is impaired by the excessive release of reactive oxygen species (ROS). Melanin, an efficient scavenger of radical species in the skin, performs a key role in ROS scavenging in response to UV radiation and is upregulated in response to toxic insult. In a chemical injury model in mice, we demonstrate that the topical application of synthetic melanin particles (SMPs) significantly decreases edema, reduces eschar detachment time, and increases the rate of wound area reduction compared to vehicle controls. Furthermore, these results were replicated in a UV-injury model. Immune array analysis shows downregulated gene expression in apoptotic and inflammatory signaling pathways consistent with histological reduction in apoptosis. Mechanistically, synthetic melanin intervention increases superoxide dismutase (SOD) activity, decreases Mmp9 expression, and suppresses ERK1/2 phosphorylation. Furthermore, we observed that the application of SMPs caused increased populations of anti-inflammatory immune cells to accumulate in the skin, mirroring their decrease from splenic populations. To enhance antioxidant capacity, an engineered biomimetic High Surface Area SMP was deployed, exhibiting increased wound healing efficiency. Finally, in human skin explants, SMP intervention significantly decreased the damage caused by chemical injury. Therefore, SMPs are promising and effective candidates as topical therapies for accelerated wound healing, including via pathways validated in human skin.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"61"},"PeriodicalIF":7.2,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10622536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71429161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Priya Mohindra, Justin X Zhong, Qizhi Fang, Darnell L Cuylear, Cindy Huynh, Huiliang Qiu, Dongwei Gao, Bhushan N Kharbikar, Xiao Huang, Matthew L Springer, Randall J Lee, Tejal A Desai
{"title":"Local decorin delivery via hyaluronic acid microrods improves cardiac performance, ventricular remodeling after myocardial infarction.","authors":"Priya Mohindra, Justin X Zhong, Qizhi Fang, Darnell L Cuylear, Cindy Huynh, Huiliang Qiu, Dongwei Gao, Bhushan N Kharbikar, Xiao Huang, Matthew L Springer, Randall J Lee, Tejal A Desai","doi":"10.1038/s41536-023-00336-w","DOIUrl":"10.1038/s41536-023-00336-w","url":null,"abstract":"<p><p>Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"8 1","pages":"60"},"PeriodicalIF":7.2,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}