Elif Kayaalp Nalbant, Timothy J Feliciano, Aliakbar Mohammadlou, Vincent L Xiong, Jacquelyn E Trujillo, Andrea E Calvert, Nihal Kaplan, Parisa Foroozandeh, Jayden Kim, Emma M Bai, Xiaolin Qi, Fernando Tobias, Eric W Roth, Vinayak P Dravid, Kurt Q Lu, SonBinh T Nguyen, C Shad Thaxton, Han Peng, Robert M Lavker
{"title":"A novel therapy to ameliorate nitrogen mustard-induced limbal stem cell deficiency using lipoprotein-like nanoparticles.","authors":"Elif Kayaalp Nalbant, Timothy J Feliciano, Aliakbar Mohammadlou, Vincent L Xiong, Jacquelyn E Trujillo, Andrea E Calvert, Nihal Kaplan, Parisa Foroozandeh, Jayden Kim, Emma M Bai, Xiaolin Qi, Fernando Tobias, Eric W Roth, Vinayak P Dravid, Kurt Q Lu, SonBinh T Nguyen, C Shad Thaxton, Han Peng, Robert M Lavker","doi":"10.1038/s41536-025-00402-5","DOIUrl":"10.1038/s41536-025-00402-5","url":null,"abstract":"<p><p>Chronic corneal inflammation, a component of sulfur mustard (SM) and nitrogen mustard (NM) injuries frequently leads to limbal stem cell deficiency (LSCD), which can compromise vision. Corneal conjunctivalization, neovascularization, and persistent inflammation are hallmarks of LSCD. Ocular exposure to SM and NM results in an acute and delayed phase of corneal disruption, culminating in LSCD. Available therapies for mustard keratopathy (e.g., topical corticosteroids) often have adverse side effects, and generally are ineffective in preventing the development of LSCD. We developed a novel, optically transparent HDL nanoparticle (NP) with an organic core (oc) molecular scaffold. This unique oc-HDL NP: (i) markedly improved corneal haze during the acute and delayed phases in vivo; (ii) significantly reduced the inflammatory response; and (iii) blunted conjunctivalization and corneal neovascularization during the delayed phase. These findings strongly suggest that our HDL NP is an ideal treatment for mustard keratopathy and other chronic corneal inflammatory diseases.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"14"},"PeriodicalIF":6.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671852","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}
Bita Nasiri, Arundhati Das, Karthik Ramachandran, Sai Harsha Bhamidipati, Yulun Wu, Shriramprasad Venkatesan, Rudiyanto Gunawan, Daniel D Swartz, Stelios T Andreadis
{"title":"Immune-mediated regeneration of cell-free vascular grafts in an ovine model.","authors":"Bita Nasiri, Arundhati Das, Karthik Ramachandran, Sai Harsha Bhamidipati, Yulun Wu, Shriramprasad Venkatesan, Rudiyanto Gunawan, Daniel D Swartz, Stelios T Andreadis","doi":"10.1038/s41536-025-00400-7","DOIUrl":"10.1038/s41536-025-00400-7","url":null,"abstract":"<p><p>We developed acellular tissue engineered vessels (ATEV) using small intestine submucosa (SIS) incorporating heparin and a novel protein named H2R5. ATEVs were implanted into the arterial circulation of an ovine animal model, demonstrating high primary patency rates over a period of three months. Implanted grafts were infiltrated by host cells, the majority of which were monocytes/macrophages (MC/MΦ), as demonstrated by scRNA sequencing and immunostaining. They also developed functional endothelial and medial layers that deposited new extracellular matrix leading to matrix remodeling and acquisition of mechanical properties that were similar to those of native arteries. Notably, during this short implantation time, ATEVs turned into functional neo-arteries, as evidenced by the development of the vascular contractile function. Our findings underscore the potential of H2R5-functionalized ATEVs as promising candidates for tissue replacement grafts in a large pre-clinical animal model and highlight the contribution of macrophages in vascular regeneration.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"13"},"PeriodicalIF":6.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665318","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}
Areli Rodriguez Ayala, George Christ, Donald Griffin
{"title":"Cell-scale porosity minimizes foreign body reaction and promotes innervated myofiber formation after volumetric muscle loss.","authors":"Areli Rodriguez Ayala, George Christ, Donald Griffin","doi":"10.1038/s41536-025-00395-1","DOIUrl":"10.1038/s41536-025-00395-1","url":null,"abstract":"<p><p>Volumetric muscle loss (VML) from severe traumatic injuries results in irreversible loss of contractile tissue and permanent functional deficits. These injuries resist endogenous healing and clinical treatment due to excessive inflammation, leading to fibrosis, muscle fiber denervation, and impaired regeneration. Using a rodent tibialis anterior VML model, this study demonstrates microporous annealed particle (MAP) hydrogel scaffolds as a biomaterial platform for improved muscle regeneration. Unlike bulk (nanoporous) hydrogel scaffolds, MAP scaffolds enhance integration by preventing a foreign body reaction, slowing implant degradation, and promoting regenerative macrophage polarization. Cell migration and angiogenesis occur throughout the implant before MAP scaffold degradation, with muscle fibers and neuromuscular junctions forming within the scaffolds. These structures continue developing as the implant degrades, suggesting MAP hydrogel scaffolds offer a promising therapeutic approach for VML injuries.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"12"},"PeriodicalIF":6.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538166","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}
Feini Qu, Kristin L Lenz, Gwendalyn L Krekeler, Xin Duan, Muhammad Farooq Rai, Farshid Guilak
{"title":"Digit regeneration is expedited in LG/J healer mice compared to SM/J non-healer mice.","authors":"Feini Qu, Kristin L Lenz, Gwendalyn L Krekeler, Xin Duan, Muhammad Farooq Rai, Farshid Guilak","doi":"10.1038/s41536-025-00399-x","DOIUrl":"10.1038/s41536-025-00399-x","url":null,"abstract":"<p><p>Limb loss resulting from disease or trauma affects an estimated 185,000 Americans annually, significantly reducing their quality of life. Consequently, successful attempts to regrow missing appendages could substantially improve the prognosis for amputees. In mice, the digit tip spontaneously regenerates resected tissues following distal amputation, whereas this capacity diminishes at more proximal levels after amputation. Moreover, regenerative potential is influenced by genetic variations among inbred mouse strains: LG/J (healer) mice exhibit superior reparative potential compared to SM/J (non-healer) mice. This study investigated the response to various levels of digit amputation in these mice to determine whether this strain-dependent healing response translates to the regeneration of complex tissues. Evaluation of skeletal regrowth, cell proliferation, and differential gene and protein expression reveals that digit regeneration is more robust in LG/J mice compared to SM/J mice at multiple amputation levels, suggesting that the regenerative capacity of composite tissues is genetically heritable in mice.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"11"},"PeriodicalIF":6.4,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426610","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}
Sarah Barbara Zwingelberg, Gizem Karabiyik, Paul Gehle, Melanie von Brandenstein, Sabina Eibichova, Christian Lotz, Florian Groeber-Becker, Daniel Kampik, Ula Jurkunas, Gerd Geerling, Gregor Lang
{"title":"Advancements in bioengineering for descemet membrane endothelial keratoplasty (DMEK).","authors":"Sarah Barbara Zwingelberg, Gizem Karabiyik, Paul Gehle, Melanie von Brandenstein, Sabina Eibichova, Christian Lotz, Florian Groeber-Becker, Daniel Kampik, Ula Jurkunas, Gerd Geerling, Gregor Lang","doi":"10.1038/s41536-025-00396-0","DOIUrl":"10.1038/s41536-025-00396-0","url":null,"abstract":"<p><p>Corneal diseases are the third leading cause of blindness worldwide. Descemet's Membrane Endothelial Keratoplasty (DMEK) is the preferred surgical technique for treating corneal endothelial disorders, relying heavily on high-quality donor tissue. However, the scarcity of suitable donor tissue and the sensitivity of endothelial cells remain significant challenges. This review explores the current state of DMEK, focusing on advancements in tissue engineering as a promising solution to improve outcomes and address donor limitations.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"10"},"PeriodicalIF":6.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426609","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}
Ricardo Whitaker, Samuel Sung, Tina Tylek, Gregory E Risser, Erin M O'Brien, Phoebe Ellin Chua, Thomas Li, Ryan J Petrie, Lin Han, Benjamin I Binder-Markey, Kara L Spiller
{"title":"Effects of injury size on local and systemic immune cell dynamics in volumetric muscle loss.","authors":"Ricardo Whitaker, Samuel Sung, Tina Tylek, Gregory E Risser, Erin M O'Brien, Phoebe Ellin Chua, Thomas Li, Ryan J Petrie, Lin Han, Benjamin I Binder-Markey, Kara L Spiller","doi":"10.1038/s41536-025-00397-z","DOIUrl":"10.1038/s41536-025-00397-z","url":null,"abstract":"<p><p>We took a systems approach to the analysis of macrophage phenotype in regenerative and fibrotic volumetric muscle loss outcomes in mice together with analysis of systemic inflammation and of other leukocytes in the muscle, spleen, and bone marrow. Differences in expression of macrophage phenotype markers occurred as early as day 1, persisted to at least day 28, and were associated with increased numbers of leukocytes in the muscle and bone marrow, increased pro-inflammatory marker expression in splenic macrophages, and changes in the levels of pro-inflammatory cytokines in the blood. The most prominent differences were in muscle neutrophils, which were much more abundant in fibrotic outcomes compared to regenerative outcomes at day 1 after injury. However, neutrophil depletion had little to no effect on macrophage phenotype or on muscle repair outcomes. Together, these results suggest that the entire system of immune cell interactions must be considered to improve muscle repair outcomes.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"9"},"PeriodicalIF":6.4,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411501","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}
Margeaux Hodgson-Garms, Matthew J Moore, Mikaël M Martino, Kilian Kelly, Jessica E Frith
{"title":"Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing.","authors":"Margeaux Hodgson-Garms, Matthew J Moore, Mikaël M Martino, Kilian Kelly, Jessica E Frith","doi":"10.1038/s41536-024-00382-y","DOIUrl":"10.1038/s41536-024-00382-y","url":null,"abstract":"<p><p>Much of the therapeutic potential of mesenchymal stromal cells (MSCs) is underpinned by their secretome which varies significantly with source, donor and microenvironmental cues. Understanding these differences is essential to define the mechanisms of MSC-based tissue repair and optimise cell therapies. This study analysed the secretomes of bone-marrow (BM.MSCs), umbilical-cord (UC.MSCs), adipose-tissue (AT.MSCs) and clinical/commercial-grade induced pluripotent stem cell-derived MSCs (iMSCs), under resting and inflammatory licenced conditions. iMSCs recapitulated the inflammatory licensing process, validating their comparability to tissue-derived MSCs. Overall, resting secretomes were defined by extracellular matrix (ECM) and pro-regenerative proteins, while licensed secretomes were enriched in chemotactic and immunomodulatory proteins. iMSC and UC.MSC secretomes contained proteins indicating proliferative potential and telomere maintenance, whereas adult tissue-derived secretomes contained fibrotic and ECM-related proteins. The data and findings from this study will inform the optimum MSC source for particular applications and underpin further development of MSC therapies.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"7"},"PeriodicalIF":6.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191182","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}
Fang Chen, Uiyoung Han, Thitima Wungcharoen, Youngyoon Amy Seo, Peter Le, Li Jiang, Nae-Won Kang, Euisun Song, Kyeongwoo Jang, David Mundy, Gabriella Maria Fernandes-Cunha, Sarah Heilshorn, David Myung
{"title":"Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels.","authors":"Fang Chen, Uiyoung Han, Thitima Wungcharoen, Youngyoon Amy Seo, Peter Le, Li Jiang, Nae-Won Kang, Euisun Song, Kyeongwoo Jang, David Mundy, Gabriella Maria Fernandes-Cunha, Sarah Heilshorn, David Myung","doi":"10.1038/s41536-024-00385-9","DOIUrl":"10.1038/s41536-024-00385-9","url":null,"abstract":"<p><p>Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"8"},"PeriodicalIF":6.4,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191181","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}
Maria Elena Candela, Melisande Addison, Rhona Aird, Tak-Yung Man, Jennifer A Cartwright, Candice Ashmore-Harris, Alastair M Kilpatrick, Philip J Starkey Lewis, Anna Drape, Mark Barnett, Donna Mitchell, Colin McLean, Neil McGowan, Marc Turner, James W Dear, Stuart J Forbes
{"title":"Cryopreserved human alternatively activated macrophages promote resolution of acetaminophen-induced liver injury in mouse.","authors":"Maria Elena Candela, Melisande Addison, Rhona Aird, Tak-Yung Man, Jennifer A Cartwright, Candice Ashmore-Harris, Alastair M Kilpatrick, Philip J Starkey Lewis, Anna Drape, Mark Barnett, Donna Mitchell, Colin McLean, Neil McGowan, Marc Turner, James W Dear, Stuart J Forbes","doi":"10.1038/s41536-025-00393-3","DOIUrl":"10.1038/s41536-025-00393-3","url":null,"abstract":"<p><p>Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates. We have previously demonstrated that alternatively, activated macrophages are a potential therapeutic option to reverse acute liver injury in pre-clinical models. In this paper, we present data using cryopreserved human alternatively activated macrophages (hAAMs)-which represent a potential, rapidly available treatment suitable for use in the acute setting. In a mouse model of APAP-induced injury, peripherally injected cryopreserved hAAMs reduced liver necrosis, modulated inflammatory responses, and enhanced liver regeneration. hAAMs were effective even when administered after the therapeutic window for NAC. This cell therapy approach represents a potential treatment for APAP overdose when NAC is ineffective because liver injury is established.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"5"},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025789","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}
Axelle Bois, Catarina Grandela, James Gallant, Christine Mummery, Philippe Menasché
{"title":"Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.","authors":"Axelle Bois, Catarina Grandela, James Gallant, Christine Mummery, Philippe Menasché","doi":"10.1038/s41536-025-00394-2","DOIUrl":"10.1038/s41536-025-00394-2","url":null,"abstract":"<p><p>Myocardial infarction (MI) causes the loss of millions of cardiomyocytes, and current treatments do not address this root issue. New therapies focus on stimulating cardiomyocyte division in the adult heart, inspired by the regenerative capacities of lower vertebrates and neonatal mice. This review explores strategies for heart regeneration, offers insights into cardiomyocyte proliferation, evaluates in vivo models, and discusses integrating in vitro human cardiac models to advance cardiac regeneration research.</p>","PeriodicalId":54236,"journal":{"name":"npj Regenerative Medicine","volume":"10 1","pages":"6"},"PeriodicalIF":6.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025793","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}