Stem Cells Translational Medicine最新文献_第4页

Second generation multiple channeling using platelet-rich plasma enhances cartilage repair through recruitment of endogenous MSCs in bone marrow. 使用富血小板血浆的第二代多通道疗法通过招募骨髓中的内源性间充质干细胞增强软骨修复。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-12-16 DOI: 10.1093/stcltm/szae075

Min Ji Lee, Jian Jiang, Soo Hyun Kim, Chris Hyunchul Jo

{"title":"Second generation multiple channeling using platelet-rich plasma enhances cartilage repair through recruitment of endogenous MSCs in bone marrow.","authors":"Min Ji Lee, Jian Jiang, Soo Hyun Kim, Chris Hyunchul Jo","doi":"10.1093/stcltm/szae075","DOIUrl":"10.1093/stcltm/szae075","url":null,"abstract":"In the treatment of cartilage defects, a key factor is the adequate and specific recruitment of endogenous stem cells to the site of injury. However, the limited quantity and capability of endogenous bone marrow stem cells (BM MSCs) often result in the formation of fibrocartilage when using bone marrow stimulation (BMS) procedures. We engineered second-generation platelet-rich plasma (2G PRP) with defibrinogenating and antifibrinolytic agents for injection into the condyle of the right femur, followed by multiple channeling (MCh) 5 days later. This approach aims to enhance repair by promoting the local proliferation and migration of BM MSCs to the full-thickness knee cartilage defect (ftKD). In our in vitro study, 2G PRP increased the number of endogenous BM MSCs and their ability to migrate toward an IL-1β-induced inflammatory condition. This significance was further confirmed by in vivo proliferation results after injection of 2G PRP into the condyle of rats. Fifty-four healthy male Sprague-Dawley rats were divided into 3 groups (ftKD, MCh, 2G MCh) for 3 time points (2 weeks, 4 weeks, 8 weeks). The 2G MCh (2G PRP injection + MCh) groups significantly improved cartilage formation at 4 and 8 weeks compared to the ftKD and MCh groups. The 2G MCh initiated cartilage repair earlier than MCh and significantly enhanced up to 8 weeks. This study demonstrated that 2G PRP increased the number of BM MSCs through the enhancement of proliferation and recruitment into the injured site, thereby improving articular cartilage repair.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1213-1227"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to: Amnion membrane hydrogel and amnion membrane powder accelerate wound healing in a full thickness porcine skin wound model. 更正为羊膜水凝胶和羊膜粉能加速猪皮肤全厚度伤口模型中的伤口愈合。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-12-16 DOI: 10.1093/stcltm/szae046

引用次数: 0

Effects of microgravity on human iPSC-derived neural organoids on the International Space Station. 微重力对国际空间站上人类 iPSC 衍生神经器官组织的影响。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-12-16 DOI: 10.1093/stcltm/szae070

Davide Marotta, Laraib Ijaz, Lilianne Barbar, Madhura Nijsure, Jason Stein, Nicolette Pirjanian, Ilya Kruglikov, Twyman Clements, Jana Stoudemire, Paula Grisanti, Scott A Noggle, Jeanne F Loring, Valentina Fossati

{"title":"Effects of microgravity on human iPSC-derived neural organoids on the International Space Station.","authors":"Davide Marotta, Laraib Ijaz, Lilianne Barbar, Madhura Nijsure, Jason Stein, Nicolette Pirjanian, Ilya Kruglikov, Twyman Clements, Jana Stoudemire, Paula Grisanti, Scott A Noggle, Jeanne F Loring, Valentina Fossati","doi":"10.1093/stcltm/szae070","DOIUrl":"10.1093/stcltm/szae070","url":null,"abstract":"Research conducted on the International Space Station (ISS) in low-Earth orbit (LEO) has shown the effects of microgravity on multiple organs. To investigate the effects of microgravity on the central nervous system, we developed a unique organoid strategy for modeling specific regions of the brain that are affected by neurodegenerative diseases. We generated 3-dimensional human neural organoids from induced pluripotent stem cells (iPSCs) derived from individuals affected by primary progressive multiple sclerosis (PPMS) or Parkinson's disease (PD) and non-symptomatic controls, by differentiating them toward cortical and dopaminergic fates, respectively, and combined them with isogenic microglia. The organoids were cultured for a month using a novel sealed cryovial culture method on the International Space Station (ISS) and a parallel set that remained on Earth. Live samples were returned to Earth for analysis by RNA expression and histology and were attached to culture dishes to enable neurite outgrowth. Our results show that both cortical and dopaminergic organoids cultured in LEO had lower levels of genes associated with cell proliferation and higher levels of maturation-associated genes, suggesting that the cells matured more quickly in LEO. This study is continuing with several more missions in order to understand the mechanisms underlying accelerated maturation and to investigate other neurological diseases. Our goal is to make use of the opportunity to study neural cells in LEO to better understand and treat neurodegenerative disease on Earth and to help ameliorate potentially adverse neurological effects of space travel.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1186-1197"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring mesenchymal stem cells homing mechanisms and improvement strategies. 探索间充质干细胞归巢机制和改善策略。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-12-16 DOI: 10.1093/stcltm/szae045

Umar Sajjad, Muhammad Ahmed, M Zohaib Iqbal, Mahrukh Riaz, Muhammad Mustafa, Thomas Biedermann, Agnes S Klar

{"title":"Exploring mesenchymal stem cells homing mechanisms and improvement strategies.","authors":"Umar Sajjad, Muhammad Ahmed, M Zohaib Iqbal, Mahrukh Riaz, Muhammad Mustafa, Thomas Biedermann, Agnes S Klar","doi":"10.1093/stcltm/szae045","DOIUrl":"10.1093/stcltm/szae045","url":null,"abstract":"Mesenchymal stem cells (MSCs) are multipotent cells with high self-renewal and multilineage differentiation abilities, playing an important role in tissue healing. Recent advancements in stem cell-based technologies have offered new and promising therapeutic options in regenerative medicine. Upon tissue damage, MSCs are immediately mobilized from the bone marrow and move to the injury site via blood circulation. Notably, allogenically transplanted MSCs can also home to the damaged tissue site. Therefore, MSCs hold great therapeutic potential for curing various diseases. However, one major obstacle to this approach is attracting MSCs specifically to the injury site following systemic administration. In this review, we describe the molecular pathways governing the homing mechanism of MSCs and various strategies for improving this process, including targeted stem cell administration, target tissue modification, in vitro priming, cell surface engineering, genetic modifications, and magnetic guidance. These strategies are crucial for directing MSCs precisely to the injury site and, consequently, enhancing their migration and local tissue repair properties. Specifically, our review provides a guide to improving the therapeutic efficacy of clinical applications of MSCs through optimized in vivo administration and homing capacities.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1161-1177"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The crosstalk between primary MSCs and cancer cells in 2D and 3D cultures: potential therapeutic strategies and impact on drug resistance. 原代间充质干细胞与癌细胞在二维和三维培养物中的相互作用：潜在的治疗策略及其对耐药性的影响。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-12-16 DOI: 10.1093/stcltm/szae077

Ayesha Rehman, Sameer Kumar Panda, Martina Torsiello, Martina Marigliano, Camilla Carmela Tufano, Aditya Nigam, Zahida Parveen, Gianpaolo Papaccio, Marcella La Noce

{"title":"The crosstalk between primary MSCs and cancer cells in 2D and 3D cultures: potential therapeutic strategies and impact on drug resistance.","authors":"Ayesha Rehman, Sameer Kumar Panda, Martina Torsiello, Martina Marigliano, Camilla Carmela Tufano, Aditya Nigam, Zahida Parveen, Gianpaolo Papaccio, Marcella La Noce","doi":"10.1093/stcltm/szae077","DOIUrl":"10.1093/stcltm/szae077","url":null,"abstract":"The tumor microenvironment (TME) significantly influences cancer progression, and mesenchymal stem cells (MSCs) play a crucial role in interacting with tumor cells via paracrine signaling, affecting behaviors such as proliferation, migration, and epithelial-mesenchymal transition. While conventional 2D culture models have provided valuable insights, they cannot fully replicate the complexity and diversity of the TME. Therefore, developing 3D culture systems that better mimic in vivo conditions is essential. This review delves into the heterogeneous nature of the TME, spotlighting MSC-tumor cellular signaling and advancements in 3D culture technologies. Utilizing MSCs in cancer therapy presents opportunities to enhance treatment effectiveness and overcome resistance mechanisms. Understanding MSC interactions within the TME and leveraging 3D culture models can advance novel cancer therapies and improve clinical outcomes. Additionally, this review underscores the therapeutic potential of engineered MSCs, emphasizing their role in targeted anti-cancer treatments.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1178-1185"},"PeriodicalIF":5.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein. 间充质基质细胞衍生的小细胞外囊泡通过调节孕区蛋白防止紫外线引起的光老化。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI: 10.1093/stcltm/szae069

Zixuan Sun, Tangrong Wang, Xiaomei Hou, Wenhuan Bai, Jiali Li, Yu Li, Jiaxin Zhang, Yuzhou Zheng, Zhijing Wu, Peipei Wu, Lirong Yan, Hui Qian

{"title":"Mesenchymal stromal cells-derived small extracellular vesicles protect against UV-induced photoaging via regulating pregnancy zone protein.","authors":"Zixuan Sun, Tangrong Wang, Xiaomei Hou, Wenhuan Bai, Jiali Li, Yu Li, Jiaxin Zhang, Yuzhou Zheng, Zhijing Wu, Peipei Wu, Lirong Yan, Hui Qian","doi":"10.1093/stcltm/szae069","DOIUrl":"10.1093/stcltm/szae069","url":null,"abstract":"Ultraviolet (UV) radiation is the primary extrinsic factor in skin aging, contributing to skin photoaging, actinic keratosis (AK), and even squamous cell carcinoma (SCC). Currently, the beneficial role of mesenchymal stromal cell-derived small extracellular vesicles (MSC-sEVs) in cutaneous wound healing has been widely reported, but the field of photoaging remains to be explored. Our results suggested that human umbilical cord MSC-derived sEVs (hucMSC-sEVs) intervention could effectively alleviate skin photoaging phenotypes in vivo and in vitro, including ameliorating UV-induced histopathological changes in the skin and inhibiting oxidative stress and collagen degradation in dermal fibroblasts (DFs). Mechanistically, pretreatment with hucMSC-sEVs reversed UVA-induced down-regulation of pregnancy zone protein (PZP) in DFs, and achieved photoprotection by inhibiting matrix metalloproteinase-1 (MMP-1) expression and reducing DNA damage. Clinically, a significant decrease in PZP in AK and SCC in situ samples was observed, while a rebound appeared in the invasive SCC samples. Collectively, our findings reveal the effective role of hucMSC-sEVs in regulating PZP to combat photoaging and provide new pre-clinical evidence for the potential development of hucMSC-sEVs as an effective skin photoprotective agent.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1129-1143"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial). 基于 Muse 细胞的产品在新生儿缺氧缺血性脑病治疗性低温中的安全性和耐受性（SHIELD 试验）。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI: 10.1093/stcltm/szae071

Yoshiaki Sato, Shinobu Shimizu, Kazuto Ueda, Toshihiko Suzuki, Sakiko Suzuki, Ryosuke Miura, Masahiko Ando, Kennosuke Tsuda, Osuke Iwata, Yukako Muramatsu, Hiroyuki Kidokoro, Akihiro Hirakawa, Masahiro Hayakawa

{"title":"Safety and tolerability of a Muse cell-based product in neonatal hypoxic-ischemic encephalopathy with therapeutic hypothermia (SHIELD trial).","authors":"Yoshiaki Sato, Shinobu Shimizu, Kazuto Ueda, Toshihiko Suzuki, Sakiko Suzuki, Ryosuke Miura, Masahiko Ando, Kennosuke Tsuda, Osuke Iwata, Yukako Muramatsu, Hiroyuki Kidokoro, Akihiro Hirakawa, Masahiro Hayakawa","doi":"10.1093/stcltm/szae071","DOIUrl":"10.1093/stcltm/szae071","url":null,"abstract":"Hypoxic-ischemic encephalopathy (HIE), associated with high mortality and neurological sequelae, lacks established treatment except therapeutic hypothermia. Clinical-grade multilineage-differentiating stress-enduring (Muse) cells (CL2020) demonstrated safety and efficacy in nonclinical HIE rat models, thereby leading to an investigator-initiated clinical trial to evaluate CL2020 safety and tolerability in neonatal HIE as a single-center open-label dose-escalation study with 9 neonates with moderate-to-severe HIE who received therapeutic hypothermia. Each patient received a single intravenous injection of CL2020 cells between 5 and 14 days of age. The low-dose (3 patients) and high-dose (6 patients) groups received 1.5 × 106 and 1.5 × 107 cells/dose, respectively. The occurrence of any adverse event within 12 weeks following CL2020 administration was the primary endpoint of this trial. No significant changes in physiological signs including heart rate, blood pressure, and oxygen saturation were observed during or after administration. The only adverse event that may be related to cell administration was a mild γ-glutamyltransferase level elevation in one neonate, which spontaneously resolved without any treatment. All patients enrolled in the trial survived, and normal developmental quotients (≥ 85) in all 3 domains of the Kyoto Scale of Psychological Development 2001 were observed in 67% of the patients in this trial. CL2020 administration was demonstrated to be safe and tolerable for neonates with HIE. Considering the small number of patients, a randomized controlled confirmatory study is warranted to verify these preliminary findings and evaluate the efficacy of this therapy.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1053-1066"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of immunosuppressive drugs on efficacy of mesenchymal stem cell therapy for suppressing renal fibrosis. 免疫抑制药物对间质干细胞疗法抑制肾脏纤维化疗效的影响。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI: 10.1093/stcltm/szae073

Kisho Miyasako, Ayumu Nakashima, Naoki Ishiuchi, Yoshiki Tanaka, Keisuke Morimoto, Kensuke Sasaki, Shogo Nagamatsu, Go Matsuda, Takao Masaki

{"title":"Impact of immunosuppressive drugs on efficacy of mesenchymal stem cell therapy for suppressing renal fibrosis.","authors":"Kisho Miyasako, Ayumu Nakashima, Naoki Ishiuchi, Yoshiki Tanaka, Keisuke Morimoto, Kensuke Sasaki, Shogo Nagamatsu, Go Matsuda, Takao Masaki","doi":"10.1093/stcltm/szae073","DOIUrl":"10.1093/stcltm/szae073","url":null,"abstract":"Preemptive regenerative medicine using mesenchymal stem cells (MSCs) may provide a novel therapeutic approach to prevent the progression from organ damage to organ failure. Although immunosuppressive drugs are often used in patients with organ disorder, their impact on MSC therapy remains unclear. We investigated the effects of immunosuppressive drugs on the therapeutic efficacy of MSCs. We created unilateral ureteral obstruction models, as a well-established model of renal fibrosis, a preliminary stage of organ failure. Three immunosuppressive drugs (methylprednisolone, cyclosporine, and cyclophosphamide) were intraperitoneally administered 3 days after surgery, and MSCs were injected via tail vein the following day. Preadministration of methylprednisolone or cyclophosphamide interfered with MSC activation by reducing expression of interferon-gamma (IFN-γ) and high-mobility group box-1 protein, thus significantly attenuating the therapeutic efficacy of MSCs. Preadministration of cyclophosphamide downregulated the expression of stromal cell-derived factor-1/C-X-C motif ligand 12, which is a potent migration factor for MSCs, resulting in reduced MSC engraftment in the renal cortex. IFN-γ-preconditioned activated MSCs were unaffected by these drugs and maintained their beneficial therapeutic effects. Cyclosporine preadministration had no effect on the therapeutic efficacy of MSCs. Our study demonstrated that the administration of certain immunosuppressive drugs interfered with MSC activation and engraftment at the site of injury, resulting in a significant attenuation of their therapeutic efficacy. These findings provide crucial information for selecting patients suitable for MSC therapy. Use of MSCs preactivated with IFN-γ or other means is preferred for patients on methylprednisolone or cyclophosphamide.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1067-1085"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons. Progranulin能增强移植的人类iPS细胞衍生脑神经元的移植。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI: 10.1093/stcltm/szae066

Keitaro Yamagami, Bumpei Samata, Daisuke Doi, Ryosuke Tsuchimochi, Tetsuhiro Kikuchi, Naoya Amimoto, Megumi Ikeda, Koji Yoshimoto, Jun Takahashi

{"title":"Progranulin enhances the engraftment of transplanted human iPS cell-derived cerebral neurons.","authors":"Keitaro Yamagami, Bumpei Samata, Daisuke Doi, Ryosuke Tsuchimochi, Tetsuhiro Kikuchi, Naoya Amimoto, Megumi Ikeda, Koji Yoshimoto, Jun Takahashi","doi":"10.1093/stcltm/szae066","DOIUrl":"10.1093/stcltm/szae066","url":null,"abstract":"Cerebral organoids (COs) in cell replacement therapy offer a viable approach to reconstructing neural circuits for individuals suffering from stroke or traumatic brain injuries. Successful transplantation relies on effective engraftment and neurite extension from the grafts. Earlier research has validated the effectiveness of delaying the transplantation procedure by 1 week. Here, we hypothesized that brain tissues 1 week following a traumatic brain injury possess a more favorable environment for cell transplantation when compared to immediately after injury. We performed a transcriptomic comparison to differentiate gene expression between these 2 temporal states. In controlled in vitro conditions, recombinant human progranulin (rhPGRN) bolstered the survival rate of dissociated neurons sourced from human induced pluripotent stem cell-derived COs (hiPSC-COs) under conditions of enhanced oxidative stress. This increase in viability was attributable to a reduction in apoptosis via Akt phosphorylation. In addition, rhPGRN pretreatment before in vivo transplantation experiments augmented the engraftment efficiency of hiPSC-COs considerably and facilitated neurite elongation along the host brain's corticospinal tracts. Subsequent histological assessments at 3 months post-transplantation revealed an elevated presence of graft-derived subcerebral projection neurons-crucial elements for reconstituting neural circuits-in the rhPGRN-treated group. These outcomes highlight the potential of PGRN as a neurotrophic factor suitable for incorporation into hiPSC-CO-based cell therapies.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1113-1128"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles. 中风患者干细胞的鼻脑传递：细胞外囊泡的作用。

IF 5.4 2区医学

Stem Cells Translational Medicine Pub Date : 2024-11-12 DOI: 10.1093/stcltm/szae072

Cesar V Borlongan, Jea-Young Lee, Francesco D'Egidio, Matthieu de Kalbermatten, Ibon Garitaonandia, Raphael Guzman

{"title":"Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.","authors":"Cesar V Borlongan, Jea-Young Lee, Francesco D'Egidio, Matthieu de Kalbermatten, Ibon Garitaonandia, Raphael Guzman","doi":"10.1093/stcltm/szae072","DOIUrl":"10.1093/stcltm/szae072","url":null,"abstract":"Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.","PeriodicalId":21986,"journal":{"name":"Stem Cells Translational Medicine","volume":" ","pages":"1043-1052"},"PeriodicalIF":5.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0