Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury DOI Creative Commons
Yulin Zhao, Zhixian Wu, Yuchen Zhou

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background In recent years, the utilization of stem cell therapy and sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, most appropriate type mechanism action remain unclear at this time. This study sought to develop an SCI rat model evaluate therapeutic effects human umbilical mesenchymal (hUC‐MSC) sheets in model. Furthermore, mechanisms underlying vascular repair effect hUC‐MSC following were investigated. Methods A temperature‐responsive culture method was employed preparation sheets. The extracellular matrix (ECM) produced by hUC‐MSCs serves two distinct yet interrelated purposes. Firstly, it acts biologically active scaffold transplanted cells, facilitating their attachment proliferation. Secondly, provides mechanical support bridges stumps, thereby restoration function. formation cavity within evaluated using Hematoxylin Eosin (H&E) staining method. Subsequently, endothelial cells cultivated with conditioned medium (CM) obtained from or pro‐angiogenic impact (MSC‐CM) (CS‐CM) through CCK‐8 assay, wound healing tube assay vitro context. development glial scars, blood vessels, neurons, axons assessed immunofluorescence staining. Results comparison hUC‐MSCs, demonstrated more pronounced capacity facilitate induce regeneration newborn neurons site, while also reducing scar significantly enhancing motor function rats. Notably, under identical conditions, been associated paracrine increase ability themselves secrete growth factors. During course experiment, observed that secretion uPAR among factors present MSC‐CM CS‐CM. finding subsequently corroborated subsequent experiments, wherein promote angiogenesis via PI3K/Akt signaling pathway. Conclusion creation not only enhances biological but effectively retains locally injury. Therefore, transplantation can maximize greatly formation, promoting axons. Additionally, research findings prove activate pathway enhance angiogenesis. transfer entire sheets, absence introduction additional exogenous synthetic biomaterials, further augment potential clinical application.

Language: Английский

Intrathecal transplantation of human umbilical cord mesenchymal stem cells enhances spinal cord injury recovery: Role of miR‑124‑3p as a biomarker DOI Open Access
Ying Zheng, Yongxin Wang, Wenwen Liu

et al.

Experimental and Therapeutic Medicine, Journal Year: 2025, Volume and Issue: 29(3)

Published: Jan. 22, 2025

Spinal cord injury (SCI) is a severe condition that often leads to permanent functional impairments. The current treatment options are limited and there need for more effective treatments. Human umbilical mesenchymal stem cells (hUCMSCs) have shown promise in promoting neuroregeneration modulating immune response. In addition, miR‑124‑3p has been identified as potential biomarker monitoring the progress of neural repair, making it focus present study, which used rat model SCI evaluate effects intrathecal hUCMSC transplantation. study included three groups: A sham‑operated group, an group receiving PBS hUCMSCs. Neurological function was assessed using Basso, Beattie Bresnahan locomotor rating scale Rivlin inclined plane test on days 1, 3, 7, 14 21 post‑injury. Histological analysis hematoxylin eosin staining assess tissue morphology, Nissl neuron survival immunofluorescence detect bromodeoxyuridine (BrdU)+/neuron‑specific enolase (NSE)+ cells, indicate neurogenesis. Detection brain‑derived neurotrophic factor (BDNF) protein expression at various time points rats with spinal western blotting. quantified reverse transcription‑quantitative (RT‑q)PCR its recovery. showed significant improvements motor compared control particularly 7 revealed reduced scar formation increased group. Immunofluorescence higher number BrdU+/NSE+ indicating enhanced neurorepair‑related BDNF markedly hUCMSCs Furthermore, RT‑qPCR demonstrated marked upregulation correlated improved transplantation notably recovery following SCI, probably by neurogenesis expression. highlighted tracking These findings provided foundation future clinical applications use tool.

Language: Английский

Citations

0
Molecular insights on Eltrombopag: potential mitogen stimulants, angiogenesis, and therapeutic radioprotectant through TPO-R activation DOI Creative Commons
Rajasekaran Subbarayan,

Dhasarathdev Srinivasan,

Salman Sadullah Usmani

et al.

Platelets, Journal Year: 2024, Volume and Issue: 35(1)

Published: June 4, 2024

The purpose of this study is to investigate the molecular interactions and potential therapeutic uses Eltrombopag (EPAG), a small molecule that activates cMPL receptor. EPAG has been found be effective in increasing platelet levels alleviating thrombocytopenia. We utilized computational techniques predict confirm complex formed by ligand (EPAG) Thrombopoietin receptor (TPO-R) cMPL, elucidating role RAS, JAK-2, STAT-3, other essential elements for downstream signaling. Molecular dynamics (MD) simulations were employed evaluate stability across specific proteins, showing favorable characteristics. For first time, we examined presence TPO-R human umbilical cord mesenchymal stem cells (hUCMSC) gingival (hGMSC) proliferation. Furthermore, treatment with demonstrated angiogenesis vasculature formation endothelial lineage derived from both MSCs. It also indicated activation critical factors such as RUNX-1, GFI-1b, VEGF-A, MYB, GOF-1, FLI-1. Additional experiments confirmed could an ideal protecting against UVB radiation damage, gene expression (JAK-2, ERK-2, MCL-1, NFkB, STAT-3) protein CD90/cMPL analysis showed hUCMSC hGMSC. Overall, exhibits significant treating damage mitigating side effects radiotherapy, warranting further clinical exploration.

Language: Английский

Citations

3
3D-Printed β-TCP Scaffold as a Bone-Mimicking Environment for an Engineered Model of Osteosarcoma: In Vitro Properties and Transcriptomic Insights DOI
Ksenia Menshikh, Virginia Alessandra Gobbo, Mauro Nascimben

et al.

Published: Jan. 1, 2025

This study investigated the potential use of a 3D-printed β-tricalcium phosphate (β-TCP) scaffold as bone-mimicking environment in an advanced vitro osteosarcoma preclinical model. The compatibility with cell spheroids, endothelial cells, and primary bone marrow-derived mesenchymal stem cells (pBMSCs) was evaluated along its physicochemical characteristics. Transcriptomic analysis pBMSCs on scaffolds revealed gene expression profiles, indicating pronounced organisation extracellular matrix minor osteogenic activity. model effectively replicated significant aspects tumour microenvironment tri-culture system, dynamic perfusion enhancing metabolic developed scaffold-based employed doxorubicin cytotoxicity test. physiological significance demonstrated by distinct accumulation, contrast to spheroid monocultures. Besides limitations proposed approach terms efficient vascularisation model, this highlights β-TCP modelling support physiologically relevant models.

Language: Английский

Citations

0
3D-Printed β-TCP Scaffold as a Bone-Mimicking Environment for an Engineered Model of Osteosarcoma: In Vitro Properties and Transcriptomic Insights DOI Creative Commons
Ksenia Menshikh, Virginia Alessandra Gobbo, Mauro Nascimben

et al.

Materials Today Bio, Journal Year: 2025, Volume and Issue: 32, P. 101766 - 101766

Published: April 12, 2025

In the face of advancements in osteosarcoma research, existing preclinical models - including vitro (i.e., two- and three-dimensional cell cultures, organoids) vivo approaches xenografts, animal models) are often characterised by low translatability, limiting their predictive power for clinical outcomes. This study investigated potential use a 3D-printed β-tricalcium phosphate (β-TCP) scaffold as bone-mimicking environment an advanced model. The compatibility with spheroids, endothelial cells, primary bone marrow-derived mesenchymal stem cells (pBMSCs) was evaluated along its physicochemical characteristics. Transcriptomic analysis pBMSCs on scaffolds revealed gene expression profiles indicating pronounced extracellular matrix organisation minor osteogenic activity. model effectively replicated significant aspects tumour microenvironment tri-culture system, dynamic perfusion enhancing metabolic developed scaffold-based employed doxorubicin cytotoxicity test. physiological significance demonstrated distinct accumulation, contrast to spheroid monocultures. Despite limitations proposed approach regarding efficient vascularisation model, this highlights β-TCP modelling support physiologically relevant models.

Language: Английский

Citations

0
Multidimensional exploration of hydrogels as biological scaffolds for spinal cord regeneration: mechanisms and future perspectives DOI Creative Commons
Cheng Han, Jiao Jiao, Chan Gong

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: April 23, 2025

Spinal cord injury (SCI) is a severe condition that frequently leads to permanent disabilities and neurological dysfunction. Its progression driven by multifaceted pathophysiology, encompassing direct trauma, secondary cascades, intricate cellular molecular responses. While current therapies focus on alleviating symptoms restoring functionality, achieving effective neural regeneration in the spinal continues be significant challenge. Hydrogels, recognized for their exceptional biocompatibility, conductivity, injectability, have shown great potential as advanced scaffolds support neuronal axonal regeneration. Recently, these materials attracted interest field of SCI rehabilitation research. This review concludes recent progress hydrogel-based strategies rehabilitation, emphasizing distinct properties, underlying mechanisms, integration with bioactive molecules, stem cells, complementary biomaterials. Hydrogels foster providing tailored microenvironment, while features such self-repair, electrical controlled drug release significantly enhance therapeutic experimental models. explores hydrogel technologies applications, underscoring address challenges treatment paving way future clinical implementation.

Language: Английский

Citations

0
Mesenchymal Stem Cells for the Treatment of Spinal Cord Injury in Rat Models: A Systematic Review and Network Meta-Analysis DOI Creative Commons
Yueying Wang, Ding Yi, Chenchen Guo

et al.

Cell Transplantation, Journal Year: 2024, Volume and Issue: 33

Published: Jan. 1, 2024

Transplantation of mesenchymal stem cells (MSCs) is one the hopeful treatments for spinal cord injury (SCI). Most current studies are in animals, and less humans, optimal transplantation strategy MSCs still controversial. In this article, we explore through a network meta-analysis effects on SCI animal models. PubMed, Web Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Science Technology Journal Database (VIP), Chinese Biomedical Literature Service System (SinoMed) databases were searched by computer randomized controlled SCI. Two investigators independently completed literature screening data extraction based inclusion exclusion criteria. RevMan 5.4 software was used to assess quality included literature. Stata 16.0 standard meta-analysis. Standardized mean difference (SMD) continuous variables combine statistics calculate 95% confidence interval (95% CI). P < 0.05 considered statistically significant difference. Cochrane’s Q test I 2 value indicate magnitude heterogeneity. A random-effects model if > 50% 0.10 indicated heterogeneity between studies, conversely, fixed-effects used. Evidence diagrams drawn direct comparisons various interventions. The surface under cumulative ranking curve area (SUCRA) predict treatment each intervention. total 32 article analysis. results showed that improved motor ability after best effect achieved adipose tissue–derived stromal (ADMSCs) terms cell source intrathecal (IT) modality. For timing, when performed subacute phase. available suggests IT using ADMSCs phase may be improve functional impairment Future high-quality needed further validate study ensure reliability results.

Language: Английский

Citations

0
Cell Sheets Formation Enhances Therapeutic Effects of Human Umbilical Cord Mesenchymal Stem Cells on Spinal Cord Injury DOI Creative Commons
Yulin Zhao, Zhixian Wu, Yuchen Zhou

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(12)

Published: Dec. 1, 2024

ABSTRACT Background In recent years, the utilization of stem cell therapy and sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, most appropriate type mechanism action remain unclear at this time. This study sought to develop an SCI rat model evaluate therapeutic effects human umbilical mesenchymal (hUC‐MSC) sheets in model. Furthermore, mechanisms underlying vascular repair effect hUC‐MSC following were investigated. Methods A temperature‐responsive culture method was employed preparation sheets. The extracellular matrix (ECM) produced by hUC‐MSCs serves two distinct yet interrelated purposes. Firstly, it acts biologically active scaffold transplanted cells, facilitating their attachment proliferation. Secondly, provides mechanical support bridges stumps, thereby restoration function. formation cavity within evaluated using Hematoxylin Eosin (H&E) staining method. Subsequently, endothelial cells cultivated with conditioned medium (CM) obtained from or pro‐angiogenic impact (MSC‐CM) (CS‐CM) through CCK‐8 assay, wound healing tube assay vitro context. development glial scars, blood vessels, neurons, axons assessed immunofluorescence staining. Results comparison hUC‐MSCs, demonstrated more pronounced capacity facilitate induce regeneration newborn neurons site, while also reducing scar significantly enhancing motor function rats. Notably, under identical conditions, been associated paracrine increase ability themselves secrete growth factors. During course experiment, observed that secretion uPAR among factors present MSC‐CM CS‐CM. finding subsequently corroborated subsequent experiments, wherein promote angiogenesis via PI3K/Akt signaling pathway. Conclusion creation not only enhances biological but effectively retains locally injury. Therefore, transplantation can maximize greatly formation, promoting axons. Additionally, research findings prove activate pathway enhance angiogenesis. transfer entire sheets, absence introduction additional exogenous synthetic biomaterials, further augment potential clinical application.

Language: Английский

Citations

0